Patrice Wendling

DETROIT – A simple formula that incorporates tumor area and percentage of positive lymph nodes helps predict 5-year disease-free survival in colorectal cancer, and may be used to guide treatment, a new study suggests.

"The formula is simple and inexpensive to apply," lead author Dr. Lisa Poritz said at the annual meeting of the Central Surgical Association. All the data are in the pathology report. "It does not require genetic or biologic tests that are expensive and not available throughout the country."

Although tumor size is not part of the widely used TNM (tumor, node, metastasis) staging system, Dr. Poritz and her colleagues hypothesized that it would be important in determining disease-free survival. To test that hypothesis, they used data from pathology reports to calculate the tumor area–to-node ratio (T:N) for 63 patients with stage III colorectal cancer (CRC) who underwent resection at the Hershey (Pa.) Medical Center from January 2000 to June 2008.

Specifically, tumor area is based on the two largest tumor measures multiplied together. The percentage of positive nodes is based on the number of nodes that are positive divided by the total number of nodes harvested, then multiplied by 100. The T:N ratio is based on the tumor area divided by the percentage of positive nodes.

In all, 35 patients remained disease free at 5 years and 28 developed metastatic disease at a mean of 16.4 months, said Dr. Poritz, a colorectal surgeon at Penn State Hershey.

The mean T:N ratio was significantly higher (2.76) in the disease-free group, compared with 0.50 in the metastatic group (P = .0009), meaning that a higher ratio is a better prognostic sign, she said.

In a receiver operating characteristic analysis, T:N ratio demonstrated the highest correlation with 5-year disease-free survival at an area under the curve of 0.86 vs. 0.79 for percentage of positive nodes, 0.75 for number of positive nodes, and just 0.61 for tumor volume.

When the data were applied to a logistic regression curve, the beta0 was 1.682 and beta1 was 2.274. From these values, the risk of distant metastasis can be calculated for a specific T:N ratio. For example, a patient with a T:N ratio of 1.22 would have a 25% risk of developing metastatic disease in 5 years, compared with a 50% risk for a patient with a T:N ratio of 0.77 and a 75% risk for a patient with a T:N ratio of 0.26, Dr. Poritz said.

Notably, even after controlling for the critical factor of nodal stage, researchers found that the T:N ratio remained significant in logistic regression analysis at a P value of .008.

Dr. Poritz also presented two hypothetical patients to illustrate how the formula could be used to influence clinical decision making. Patient A had a small tumor with an area of 1.52 and 2 of 17 positive nodes. This resulted in a T:N ratio of 0.25 and a 75% risk of developing metastatic disease in 5 years. Patient B had a large tumor with an area of 28.3 and also 2 of 17 positive nodes. The T:N ratio would be 2.4, and the patient would have only a 2% chance of developing metastatic disease within 5 years.

"If you only looked at the number of nodes or [percentage of positive nodes], you might consider treating these patients in exactly the same manner, or at least consider their risk of developing metastatic cancer to be exactly the same," she said. "However, when you use our calculations, you can see that tumor volume is very important, and it changes the risk of developing metastatic disease dramatically in these patients. In this context, you might want to treat patient A more aggressively than patient B."

Invited discussant Dr. Anthony Senagore of the University of Southern California in Los Angeles asked whether data were available on the relationship between T stage and the size of the tumor, because "you seem to imply that what we historically believe about depth of penetration seems to be less important, and that it’s the mass of the tumor that matters."

Dr. Poritz replied that depth of penetration – which is included in the TNM staging system – remains important, especially in stage II and node-negative disease when clinicians are trying to determine who should receive chemotherapy. However, the data would suggest that at least within stage III disease, tumor area may be more important than T stage, which has not been shown to correlate well with prognosis either in their study or others.

An audience member remarked that the researchers may be making too big a leap in suggesting that the formula could be used to guide therapy, and asked whether they have considered taking the findings to SWOG (formerly the Southwest Oncology Group) for further validation. Dr. Poritz said that they are in the process of applying the formula to a larger database, similar to that of SWOG.

Colon cancer was present in 21 patients in the disease-free group and in 19 patients in the metastatic group, with 14 cases of rectal cancer in each group. There were no differences between the two groups with regard to sex, age, tumor location, vascular or lymphatic invasion, or T stage. Perineural invasion was significantly more common in the metastatic group than in the disease-free group (11 cases vs. 2 cases), but Dr. Poritz urged caution in interpreting this because data on perineural invasion were not mentioned in 30 cases.

As expected, significantly more patients in the metastatic group than in the disease-free group had an N stage of 2 (18 cases vs. 6 cases) or N stage of 3 (1 case vs. 0). Similarly, the mean number of positive nodes was higher in the metastatic group than in the disease-free group at 6.1 vs. 2.3 (P = .0049), as was the percentage of positive nodes at 39.6% vs. 13% (P = .0006).

The study excluded patients who had inflammatory bowel disease, associated CRC, recurrent cancer, or perforated cancer, or who had received any neoadjuvant therapy or had died of unknown causes or causes other than cancer.

The authors reported no study support or conflicts of interest.

DETROIT – A simple formula that incorporates tumor area and percentage of positive lymph nodes helps predict 5-year disease-free survival in colorectal cancer, and may be used to guide treatment, a new study suggests.

"The formula is simple and inexpensive to apply," lead author Dr. Lisa Poritz said at the annual meeting of the Central Surgical Association. All the data are in the pathology report. "It does not require genetic or biologic tests that are expensive and not available throughout the country."

Although tumor size is not part of the widely used TNM (tumor, node, metastasis) staging system, Dr. Poritz and her colleagues hypothesized that it would be important in determining disease-free survival. To test that hypothesis, they used data from pathology reports to calculate the tumor area–to-node ratio (T:N) for 63 patients with stage III colorectal cancer (CRC) who underwent resection at the Hershey (Pa.) Medical Center from January 2000 to June 2008.

Specifically, tumor area is based on the two largest tumor measures multiplied together. The percentage of positive nodes is based on the number of nodes that are positive divided by the total number of nodes harvested, then multiplied by 100. The T:N ratio is based on the tumor area divided by the percentage of positive nodes.

In all, 35 patients remained disease free at 5 years and 28 developed metastatic disease at a mean of 16.4 months, said Dr. Poritz, a colorectal surgeon at Penn State Hershey.

The mean T:N ratio was significantly higher (2.76) in the disease-free group, compared with 0.50 in the metastatic group (P = .0009), meaning that a higher ratio is a better prognostic sign, she said.

In a receiver operating characteristic analysis, T:N ratio demonstrated the highest correlation with 5-year disease-free survival at an area under the curve of 0.86 vs. 0.79 for percentage of positive nodes, 0.75 for number of positive nodes, and just 0.61 for tumor volume.

When the data were applied to a logistic regression curve, the beta0 was 1.682 and beta1 was 2.274. From these values, the risk of distant metastasis can be calculated for a specific T:N ratio. For example, a patient with a T:N ratio of 1.22 would have a 25% risk of developing metastatic disease in 5 years, compared with a 50% risk for a patient with a T:N ratio of 0.77 and a 75% risk for a patient with a T:N ratio of 0.26, Dr. Poritz said.

Notably, even after controlling for the critical factor of nodal stage, researchers found that the T:N ratio remained significant in logistic regression analysis at a P value of .008.

Dr. Poritz also presented two hypothetical patients to illustrate how the formula could be used to influence clinical decision making. Patient A had a small tumor with an area of 1.52 and 2 of 17 positive nodes. This resulted in a T:N ratio of 0.25 and a 75% risk of developing metastatic disease in 5 years. Patient B had a large tumor with an area of 28.3 and also 2 of 17 positive nodes. The T:N ratio would be 2.4, and the patient would have only a 2% chance of developing metastatic disease within 5 years.

"If you only looked at the number of nodes or [percentage of positive nodes], you might consider treating these patients in exactly the same manner, or at least consider their risk of developing metastatic cancer to be exactly the same," she said. "However, when you use our calculations, you can see that tumor volume is very important, and it changes the risk of developing metastatic disease dramatically in these patients. In this context, you might want to treat patient A more aggressively than patient B."

Invited discussant Dr. Anthony Senagore of the University of Southern California in Los Angeles asked whether data were available on the relationship between T stage and the size of the tumor, because "you seem to imply that what we historically believe about depth of penetration seems to be less important, and that it’s the mass of the tumor that matters."

Dr. Poritz replied that depth of penetration – which is included in the TNM staging system – remains important, especially in stage II and node-negative disease when clinicians are trying to determine who should receive chemotherapy. However, the data would suggest that at least within stage III disease, tumor area may be more important than T stage, which has not been shown to correlate well with prognosis either in their study or others.

An audience member remarked that the researchers may be making too big a leap in suggesting that the formula could be used to guide therapy, and asked whether they have considered taking the findings to SWOG (formerly the Southwest Oncology Group) for further validation. Dr. Poritz said that they are in the process of applying the formula to a larger database, similar to that of SWOG.

Colon cancer was present in 21 patients in the disease-free group and in 19 patients in the metastatic group, with 14 cases of rectal cancer in each group. There were no differences between the two groups with regard to sex, age, tumor location, vascular or lymphatic invasion, or T stage. Perineural invasion was significantly more common in the metastatic group than in the disease-free group (11 cases vs. 2 cases), but Dr. Poritz urged caution in interpreting this because data on perineural invasion were not mentioned in 30 cases.

As expected, significantly more patients in the metastatic group than in the disease-free group had an N stage of 2 (18 cases vs. 6 cases) or N stage of 3 (1 case vs. 0). Similarly, the mean number of positive nodes was higher in the metastatic group than in the disease-free group at 6.1 vs. 2.3 (P = .0049), as was the percentage of positive nodes at 39.6% vs. 13% (P = .0006).

The study excluded patients who had inflammatory bowel disease, associated CRC, recurrent cancer, or perforated cancer, or who had received any neoadjuvant therapy or had died of unknown causes or causes other than cancer.

The authors reported no study support or conflicts of interest.

DETROIT – A simple formula that incorporates tumor area and percentage of positive lymph nodes helps predict 5-year disease-free survival in colorectal cancer, and may be used to guide treatment, a new study suggests.

"The formula is simple and inexpensive to apply," lead author Dr. Lisa Poritz said at the annual meeting of the Central Surgical Association. All the data are in the pathology report. "It does not require genetic or biologic tests that are expensive and not available throughout the country."

Although tumor size is not part of the widely used TNM (tumor, node, metastasis) staging system, Dr. Poritz and her colleagues hypothesized that it would be important in determining disease-free survival. To test that hypothesis, they used data from pathology reports to calculate the tumor area–to-node ratio (T:N) for 63 patients with stage III colorectal cancer (CRC) who underwent resection at the Hershey (Pa.) Medical Center from January 2000 to June 2008.

Specifically, tumor area is based on the two largest tumor measures multiplied together. The percentage of positive nodes is based on the number of nodes that are positive divided by the total number of nodes harvested, then multiplied by 100. The T:N ratio is based on the tumor area divided by the percentage of positive nodes.

In all, 35 patients remained disease free at 5 years and 28 developed metastatic disease at a mean of 16.4 months, said Dr. Poritz, a colorectal surgeon at Penn State Hershey.

The mean T:N ratio was significantly higher (2.76) in the disease-free group, compared with 0.50 in the metastatic group (P = .0009), meaning that a higher ratio is a better prognostic sign, she said.

In a receiver operating characteristic analysis, T:N ratio demonstrated the highest correlation with 5-year disease-free survival at an area under the curve of 0.86 vs. 0.79 for percentage of positive nodes, 0.75 for number of positive nodes, and just 0.61 for tumor volume.

When the data were applied to a logistic regression curve, the beta0 was 1.682 and beta1 was 2.274. From these values, the risk of distant metastasis can be calculated for a specific T:N ratio. For example, a patient with a T:N ratio of 1.22 would have a 25% risk of developing metastatic disease in 5 years, compared with a 50% risk for a patient with a T:N ratio of 0.77 and a 75% risk for a patient with a T:N ratio of 0.26, Dr. Poritz said.

Notably, even after controlling for the critical factor of nodal stage, researchers found that the T:N ratio remained significant in logistic regression analysis at a P value of .008.

Dr. Poritz also presented two hypothetical patients to illustrate how the formula could be used to influence clinical decision making. Patient A had a small tumor with an area of 1.52 and 2 of 17 positive nodes. This resulted in a T:N ratio of 0.25 and a 75% risk of developing metastatic disease in 5 years. Patient B had a large tumor with an area of 28.3 and also 2 of 17 positive nodes. The T:N ratio would be 2.4, and the patient would have only a 2% chance of developing metastatic disease within 5 years.

"If you only looked at the number of nodes or [percentage of positive nodes], you might consider treating these patients in exactly the same manner, or at least consider their risk of developing metastatic cancer to be exactly the same," she said. "However, when you use our calculations, you can see that tumor volume is very important, and it changes the risk of developing metastatic disease dramatically in these patients. In this context, you might want to treat patient A more aggressively than patient B."

Invited discussant Dr. Anthony Senagore of the University of Southern California in Los Angeles asked whether data were available on the relationship between T stage and the size of the tumor, because "you seem to imply that what we historically believe about depth of penetration seems to be less important, and that it’s the mass of the tumor that matters."

Dr. Poritz replied that depth of penetration – which is included in the TNM staging system – remains important, especially in stage II and node-negative disease when clinicians are trying to determine who should receive chemotherapy. However, the data would suggest that at least within stage III disease, tumor area may be more important than T stage, which has not been shown to correlate well with prognosis either in their study or others.

An audience member remarked that the researchers may be making too big a leap in suggesting that the formula could be used to guide therapy, and asked whether they have considered taking the findings to SWOG (formerly the Southwest Oncology Group) for further validation. Dr. Poritz said that they are in the process of applying the formula to a larger database, similar to that of SWOG.

Colon cancer was present in 21 patients in the disease-free group and in 19 patients in the metastatic group, with 14 cases of rectal cancer in each group. There were no differences between the two groups with regard to sex, age, tumor location, vascular or lymphatic invasion, or T stage. Perineural invasion was significantly more common in the metastatic group than in the disease-free group (11 cases vs. 2 cases), but Dr. Poritz urged caution in interpreting this because data on perineural invasion were not mentioned in 30 cases.

As expected, significantly more patients in the metastatic group than in the disease-free group had an N stage of 2 (18 cases vs. 6 cases) or N stage of 3 (1 case vs. 0). Similarly, the mean number of positive nodes was higher in the metastatic group than in the disease-free group at 6.1 vs. 2.3 (P = .0049), as was the percentage of positive nodes at 39.6% vs. 13% (P = .0006).

The study excluded patients who had inflammatory bowel disease, associated CRC, recurrent cancer, or perforated cancer, or who had received any neoadjuvant therapy or had died of unknown causes or causes other than cancer.

The authors reported no study support or conflicts of interest.

SAN ANTONIO – In a large but nonrandomized group of patients with primary melanoma, sentinel node biopsy significantly prolonged disease-free survival, but offered no prolongation of distant metastases free- or melanoma-specific survival.

Researchers at the Melanoma Institute Australia in North Sydney evaluated survival among 5,567 patients who from 1992 to 2008 underwent wide local excision with or without sentinel node biopsy (SNB) for a primary melanoma that was at least 1 mm thick, Clark level IV or V, or had ulceration. Median follow-up was 3.5 years.

Among the 2,803 patients who underwent SNB, 390 had a positive sentinel node (14%), followed by early complete lymph node dissection. Of the 2,413 patients with a negative sentinel node, 88 experienced regional lymph node recurrence (3.6%) and underwent delayed total lymph node dissection. This resulted in a false-negative rate for SNB of 18.4%, Mr. Stijn van der Ploeg, M.Sc., reported.

Among the 2,765 patients who underwent wide local excision with nodal observation using ultrasound, 378 experienced regional lymph node recurrence (13.7%) and underwent delayed total lymph node dissection.

In univariate analysis, patients who underwent SNB had significantly improved disease-free survival and regional lymph node metastases-free survival (both P value less than .001), but no prolongation in distant metastases-free survival (P = .85) or melanoma-specific survival (P = .49), said Mr. van der Ploeg, now a doctoral student at Erasmus Medical Center in Rotterdam, The Netherlands.

When patients were stratified by tumor thickness, melanoma-specific survival significantly improved in SNB patients with tumors 1.2 mm to 3.5 mm thick (P = .01).

Mr. van der Ploeg pointed out that there were significant differences between the two groups. The SNB group had younger patients, more nodular melanomas, and more distant recurrence as the first site of recurrence, while the observation group had thinner primary tumors, more tumors located in the head and neck, and more nodal recurrences as the first site of recurrence.

After adjusting for these and other differences – including gender, age, histological subtype, mitotic rate, Clark level, and ulceration – the researchers observed no significant benefit for SNB vs. observation for melanoma-specific survival among patients in all thickness subgroups analyzed, he said.

Finally, in univariate analysis, early complete lymph node dissection failed to significantly improve distant metastases-free survival or melanoma-specific survival among SNB-positive patients of all thickness subgroups. There was a trend toward improved distant metastases free-survival favoring early vs. late dissection among patients with intermediate-thickness melanoma (P = .060).

"Our study suggests that patients with intermediate-thickness melanomas 1.2 [mm] to 3.5 [mm] are most likely to have therapeutic benefit from undergoing sentinel node biopsy," Mr. van der Ploeg concluded.

He added that the final results of the Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) are awaited with great interest, to better define melanoma patient subgroups most likely to obtain a survival benefit from SNB.

Interim analyses from MSLT-1 have confirmed that disease-free and distant disease-free survival are improved with SNB among patients with intermediate-thickness melanomas, but the long-running trial has failed to show a definitive overall survival advantage for the procedure.

During a discussion of the Australian study, audience members asked what techniques were used for SNB, remarking that the false-negative rate of 18% is well above the 4% rate reached by many groups today. Mr. van der Ploeg said the false-negative rate has fallen over time with more experience to 15%, and that surgeons use blue dye, but not the 10% rule during lymph node mapping.

The authors reported no disclosures.

SAN ANTONIO – In a large but nonrandomized group of patients with primary melanoma, sentinel node biopsy significantly prolonged disease-free survival, but offered no prolongation of distant metastases free- or melanoma-specific survival.

Researchers at the Melanoma Institute Australia in North Sydney evaluated survival among 5,567 patients who from 1992 to 2008 underwent wide local excision with or without sentinel node biopsy (SNB) for a primary melanoma that was at least 1 mm thick, Clark level IV or V, or had ulceration. Median follow-up was 3.5 years.

Among the 2,803 patients who underwent SNB, 390 had a positive sentinel node (14%), followed by early complete lymph node dissection. Of the 2,413 patients with a negative sentinel node, 88 experienced regional lymph node recurrence (3.6%) and underwent delayed total lymph node dissection. This resulted in a false-negative rate for SNB of 18.4%, Mr. Stijn van der Ploeg, M.Sc., reported.

Among the 2,765 patients who underwent wide local excision with nodal observation using ultrasound, 378 experienced regional lymph node recurrence (13.7%) and underwent delayed total lymph node dissection.

In univariate analysis, patients who underwent SNB had significantly improved disease-free survival and regional lymph node metastases-free survival (both P value less than .001), but no prolongation in distant metastases-free survival (P = .85) or melanoma-specific survival (P = .49), said Mr. van der Ploeg, now a doctoral student at Erasmus Medical Center in Rotterdam, The Netherlands.

When patients were stratified by tumor thickness, melanoma-specific survival significantly improved in SNB patients with tumors 1.2 mm to 3.5 mm thick (P = .01).

Mr. van der Ploeg pointed out that there were significant differences between the two groups. The SNB group had younger patients, more nodular melanomas, and more distant recurrence as the first site of recurrence, while the observation group had thinner primary tumors, more tumors located in the head and neck, and more nodal recurrences as the first site of recurrence.

After adjusting for these and other differences – including gender, age, histological subtype, mitotic rate, Clark level, and ulceration – the researchers observed no significant benefit for SNB vs. observation for melanoma-specific survival among patients in all thickness subgroups analyzed, he said.

Finally, in univariate analysis, early complete lymph node dissection failed to significantly improve distant metastases-free survival or melanoma-specific survival among SNB-positive patients of all thickness subgroups. There was a trend toward improved distant metastases free-survival favoring early vs. late dissection among patients with intermediate-thickness melanoma (P = .060).

"Our study suggests that patients with intermediate-thickness melanomas 1.2 [mm] to 3.5 [mm] are most likely to have therapeutic benefit from undergoing sentinel node biopsy," Mr. van der Ploeg concluded.

He added that the final results of the Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) are awaited with great interest, to better define melanoma patient subgroups most likely to obtain a survival benefit from SNB.

Interim analyses from MSLT-1 have confirmed that disease-free and distant disease-free survival are improved with SNB among patients with intermediate-thickness melanomas, but the long-running trial has failed to show a definitive overall survival advantage for the procedure.

During a discussion of the Australian study, audience members asked what techniques were used for SNB, remarking that the false-negative rate of 18% is well above the 4% rate reached by many groups today. Mr. van der Ploeg said the false-negative rate has fallen over time with more experience to 15%, and that surgeons use blue dye, but not the 10% rule during lymph node mapping.

The authors reported no disclosures.

SAN ANTONIO – In a large but nonrandomized group of patients with primary melanoma, sentinel node biopsy significantly prolonged disease-free survival, but offered no prolongation of distant metastases free- or melanoma-specific survival.

Researchers at the Melanoma Institute Australia in North Sydney evaluated survival among 5,567 patients who from 1992 to 2008 underwent wide local excision with or without sentinel node biopsy (SNB) for a primary melanoma that was at least 1 mm thick, Clark level IV or V, or had ulceration. Median follow-up was 3.5 years.

Among the 2,803 patients who underwent SNB, 390 had a positive sentinel node (14%), followed by early complete lymph node dissection. Of the 2,413 patients with a negative sentinel node, 88 experienced regional lymph node recurrence (3.6%) and underwent delayed total lymph node dissection. This resulted in a false-negative rate for SNB of 18.4%, Mr. Stijn van der Ploeg, M.Sc., reported.

Among the 2,765 patients who underwent wide local excision with nodal observation using ultrasound, 378 experienced regional lymph node recurrence (13.7%) and underwent delayed total lymph node dissection.

In univariate analysis, patients who underwent SNB had significantly improved disease-free survival and regional lymph node metastases-free survival (both P value less than .001), but no prolongation in distant metastases-free survival (P = .85) or melanoma-specific survival (P = .49), said Mr. van der Ploeg, now a doctoral student at Erasmus Medical Center in Rotterdam, The Netherlands.

When patients were stratified by tumor thickness, melanoma-specific survival significantly improved in SNB patients with tumors 1.2 mm to 3.5 mm thick (P = .01).

Mr. van der Ploeg pointed out that there were significant differences between the two groups. The SNB group had younger patients, more nodular melanomas, and more distant recurrence as the first site of recurrence, while the observation group had thinner primary tumors, more tumors located in the head and neck, and more nodal recurrences as the first site of recurrence.

After adjusting for these and other differences – including gender, age, histological subtype, mitotic rate, Clark level, and ulceration – the researchers observed no significant benefit for SNB vs. observation for melanoma-specific survival among patients in all thickness subgroups analyzed, he said.

Finally, in univariate analysis, early complete lymph node dissection failed to significantly improve distant metastases-free survival or melanoma-specific survival among SNB-positive patients of all thickness subgroups. There was a trend toward improved distant metastases free-survival favoring early vs. late dissection among patients with intermediate-thickness melanoma (P = .060).

"Our study suggests that patients with intermediate-thickness melanomas 1.2 [mm] to 3.5 [mm] are most likely to have therapeutic benefit from undergoing sentinel node biopsy," Mr. van der Ploeg concluded.

He added that the final results of the Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) are awaited with great interest, to better define melanoma patient subgroups most likely to obtain a survival benefit from SNB.

Interim analyses from MSLT-1 have confirmed that disease-free and distant disease-free survival are improved with SNB among patients with intermediate-thickness melanomas, but the long-running trial has failed to show a definitive overall survival advantage for the procedure.

During a discussion of the Australian study, audience members asked what techniques were used for SNB, remarking that the false-negative rate of 18% is well above the 4% rate reached by many groups today. Mr. van der Ploeg said the false-negative rate has fallen over time with more experience to 15%, and that surgeons use blue dye, but not the 10% rule during lymph node mapping.

The authors reported no disclosures.

SAN ANTONIO – In a large but nonrandomized group of patients with primary melanoma, sentinel node biopsy significantly prolonged disease-free survival, but offered no prolongation of distant metastases free- or melanoma-specific survival.

Researchers at the Melanoma Institute Australia in North Sydney evaluated survival among 5,567 patients who from 1992 to 2008 underwent wide local excision with or without sentinel node biopsy (SNB) for a primary melanoma that was at least 1 mm thick, Clark level IV or V, or had ulceration. Median follow-up was 3.5 years.

Among the 2,803 patients who underwent SNB, 390 had a positive sentinel node (14%), followed by early complete lymph node dissection. Of the 2,413 patients with a negative sentinel node, 88 experienced regional lymph node recurrence (3.6%) and underwent delayed total lymph node dissection. This resulted in a false-negative rate for SNB of 18.4%, Mr. Stijn van der Ploeg, M.Sc., reported.

Among the 2,765 patients who underwent wide local excision with nodal observation using ultrasound, 378 experienced regional lymph node recurrence (13.7%) and underwent delayed total lymph node dissection.

In univariate analysis, patients who underwent SNB had significantly improved disease-free survival and regional lymph node metastases-free survival (both P value less than .001), but no prolongation in distant metastases-free survival (P = .85) or melanoma-specific survival (P = .49), said Mr. van der Ploeg, now a doctoral student at Erasmus Medical Center in Rotterdam, The Netherlands.

When patients were stratified by tumor thickness, melanoma-specific survival significantly improved in SNB patients with tumors 1.2 mm to 3.5 mm thick (P = .01).

Mr. van der Ploeg pointed out that there were significant differences between the two groups. The SNB group had younger patients, more nodular melanomas, and more distant recurrence as the first site of recurrence, while the observation group had thinner primary tumors, more tumors located in the head and neck, and more nodal recurrences as the first site of recurrence.

After adjusting for these and other differences – including gender, age, histological subtype, mitotic rate, Clark level, and ulceration – the researchers observed no significant benefit for SNB vs. observation for melanoma-specific survival among patients in all thickness subgroups analyzed, he said.

Finally, in univariate analysis, early complete lymph node dissection failed to significantly improve distant metastases-free survival or melanoma-specific survival among SNB-positive patients of all thickness subgroups. There was a trend toward improved distant metastases free-survival favoring early vs. late dissection among patients with intermediate-thickness melanoma (P = .060).

"Our study suggests that patients with intermediate-thickness melanomas 1.2 [mm] to 3.5 [mm] are most likely to have therapeutic benefit from undergoing sentinel node biopsy," Mr. van der Ploeg concluded.

He added that the final results of the Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) are awaited with great interest, to better define melanoma patient subgroups most likely to obtain a survival benefit from SNB.

Interim analyses from MSLT-1 have confirmed that disease-free and distant disease-free survival are improved with SNB among patients with intermediate-thickness melanomas, but the long-running trial has failed to show a definitive overall survival advantage for the procedure.

During a discussion of the Australian study, audience members asked what techniques were used for SNB, remarking that the false-negative rate of 18% is well above the 4% rate reached by many groups today. Mr. van der Ploeg said the false-negative rate has fallen over time with more experience to 15%, and that surgeons use blue dye, but not the 10% rule during lymph node mapping.

The authors reported no disclosures.

SAN ANTONIO – In a large but nonrandomized group of patients with primary melanoma, sentinel node biopsy significantly prolonged disease-free survival, but offered no prolongation of distant metastases free- or melanoma-specific survival.

Researchers at the Melanoma Institute Australia in North Sydney evaluated survival among 5,567 patients who from 1992 to 2008 underwent wide local excision with or without sentinel node biopsy (SNB) for a primary melanoma that was at least 1 mm thick, Clark level IV or V, or had ulceration. Median follow-up was 3.5 years.

Among the 2,803 patients who underwent SNB, 390 had a positive sentinel node (14%), followed by early complete lymph node dissection. Of the 2,413 patients with a negative sentinel node, 88 experienced regional lymph node recurrence (3.6%) and underwent delayed total lymph node dissection. This resulted in a false-negative rate for SNB of 18.4%, Mr. Stijn van der Ploeg, M.Sc., reported.

Among the 2,765 patients who underwent wide local excision with nodal observation using ultrasound, 378 experienced regional lymph node recurrence (13.7%) and underwent delayed total lymph node dissection.

In univariate analysis, patients who underwent SNB had significantly improved disease-free survival and regional lymph node metastases-free survival (both P value less than .001), but no prolongation in distant metastases-free survival (P = .85) or melanoma-specific survival (P = .49), said Mr. van der Ploeg, now a doctoral student at Erasmus Medical Center in Rotterdam, The Netherlands.

When patients were stratified by tumor thickness, melanoma-specific survival significantly improved in SNB patients with tumors 1.2 mm to 3.5 mm thick (P = .01).

Mr. van der Ploeg pointed out that there were significant differences between the two groups. The SNB group had younger patients, more nodular melanomas, and more distant recurrence as the first site of recurrence, while the observation group had thinner primary tumors, more tumors located in the head and neck, and more nodal recurrences as the first site of recurrence.

After adjusting for these and other differences – including gender, age, histological subtype, mitotic rate, Clark level, and ulceration – the researchers observed no significant benefit for SNB vs. observation for melanoma-specific survival among patients in all thickness subgroups analyzed, he said.

Finally, in univariate analysis, early complete lymph node dissection failed to significantly improve distant metastases-free survival or melanoma-specific survival among SNB-positive patients of all thickness subgroups. There was a trend toward improved distant metastases free-survival favoring early vs. late dissection among patients with intermediate-thickness melanoma (P = .060).

"Our study suggests that patients with intermediate-thickness melanomas 1.2 [mm] to 3.5 [mm] are most likely to have therapeutic benefit from undergoing sentinel node biopsy," Mr. van der Ploeg concluded.

He added that the final results of the Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) are awaited with great interest, to better define melanoma patient subgroups most likely to obtain a survival benefit from SNB.

Interim analyses from MSLT-1 have confirmed that disease-free and distant disease-free survival are improved with SNB among patients with intermediate-thickness melanomas, but the long-running trial has failed to show a definitive overall survival advantage for the procedure.

During a discussion of the Australian study, audience members asked what techniques were used for SNB, remarking that the false-negative rate of 18% is well above the 4% rate reached by many groups today. Mr. van der Ploeg said the false-negative rate has fallen over time with more experience to 15%, and that surgeons use blue dye, but not the 10% rule during lymph node mapping.

The authors reported no disclosures.

SAN ANTONIO – In a large but nonrandomized group of patients with primary melanoma, sentinel node biopsy significantly prolonged disease-free survival, but offered no prolongation of distant metastases free- or melanoma-specific survival.

Researchers at the Melanoma Institute Australia in North Sydney evaluated survival among 5,567 patients who from 1992 to 2008 underwent wide local excision with or without sentinel node biopsy (SNB) for a primary melanoma that was at least 1 mm thick, Clark level IV or V, or had ulceration. Median follow-up was 3.5 years.

Among the 2,803 patients who underwent SNB, 390 had a positive sentinel node (14%), followed by early complete lymph node dissection. Of the 2,413 patients with a negative sentinel node, 88 experienced regional lymph node recurrence (3.6%) and underwent delayed total lymph node dissection. This resulted in a false-negative rate for SNB of 18.4%, Mr. Stijn van der Ploeg, M.Sc., reported.

Among the 2,765 patients who underwent wide local excision with nodal observation using ultrasound, 378 experienced regional lymph node recurrence (13.7%) and underwent delayed total lymph node dissection.

In univariate analysis, patients who underwent SNB had significantly improved disease-free survival and regional lymph node metastases-free survival (both P value less than .001), but no prolongation in distant metastases-free survival (P = .85) or melanoma-specific survival (P = .49), said Mr. van der Ploeg, now a doctoral student at Erasmus Medical Center in Rotterdam, The Netherlands.

When patients were stratified by tumor thickness, melanoma-specific survival significantly improved in SNB patients with tumors 1.2 mm to 3.5 mm thick (P = .01).

Mr. van der Ploeg pointed out that there were significant differences between the two groups. The SNB group had younger patients, more nodular melanomas, and more distant recurrence as the first site of recurrence, while the observation group had thinner primary tumors, more tumors located in the head and neck, and more nodal recurrences as the first site of recurrence.

After adjusting for these and other differences – including gender, age, histological subtype, mitotic rate, Clark level, and ulceration – the researchers observed no significant benefit for SNB vs. observation for melanoma-specific survival among patients in all thickness subgroups analyzed, he said.

Finally, in univariate analysis, early complete lymph node dissection failed to significantly improve distant metastases-free survival or melanoma-specific survival among SNB-positive patients of all thickness subgroups. There was a trend toward improved distant metastases free-survival favoring early vs. late dissection among patients with intermediate-thickness melanoma (P = .060).

"Our study suggests that patients with intermediate-thickness melanomas 1.2 [mm] to 3.5 [mm] are most likely to have therapeutic benefit from undergoing sentinel node biopsy," Mr. van der Ploeg concluded.

He added that the final results of the Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) are awaited with great interest, to better define melanoma patient subgroups most likely to obtain a survival benefit from SNB.

Interim analyses from MSLT-1 have confirmed that disease-free and distant disease-free survival are improved with SNB among patients with intermediate-thickness melanomas, but the long-running trial has failed to show a definitive overall survival advantage for the procedure.

During a discussion of the Australian study, audience members asked what techniques were used for SNB, remarking that the false-negative rate of 18% is well above the 4% rate reached by many groups today. Mr. van der Ploeg said the false-negative rate has fallen over time with more experience to 15%, and that surgeons use blue dye, but not the 10% rule during lymph node mapping.

The authors reported no disclosures.

SAN ANTONIO – In a large but nonrandomized group of patients with primary melanoma, sentinel node biopsy significantly prolonged disease-free survival, but offered no prolongation of distant metastases free- or melanoma-specific survival.

Researchers at the Melanoma Institute Australia in North Sydney evaluated survival among 5,567 patients who from 1992 to 2008 underwent wide local excision with or without sentinel node biopsy (SNB) for a primary melanoma that was at least 1 mm thick, Clark level IV or V, or had ulceration. Median follow-up was 3.5 years.

Among the 2,803 patients who underwent SNB, 390 had a positive sentinel node (14%), followed by early complete lymph node dissection. Of the 2,413 patients with a negative sentinel node, 88 experienced regional lymph node recurrence (3.6%) and underwent delayed total lymph node dissection. This resulted in a false-negative rate for SNB of 18.4%, Mr. Stijn van der Ploeg, M.Sc., reported.

Among the 2,765 patients who underwent wide local excision with nodal observation using ultrasound, 378 experienced regional lymph node recurrence (13.7%) and underwent delayed total lymph node dissection.

In univariate analysis, patients who underwent SNB had significantly improved disease-free survival and regional lymph node metastases-free survival (both P value less than .001), but no prolongation in distant metastases-free survival (P = .85) or melanoma-specific survival (P = .49), said Mr. van der Ploeg, now a doctoral student at Erasmus Medical Center in Rotterdam, The Netherlands.

When patients were stratified by tumor thickness, melanoma-specific survival significantly improved in SNB patients with tumors 1.2 mm to 3.5 mm thick (P = .01).

Mr. van der Ploeg pointed out that there were significant differences between the two groups. The SNB group had younger patients, more nodular melanomas, and more distant recurrence as the first site of recurrence, while the observation group had thinner primary tumors, more tumors located in the head and neck, and more nodal recurrences as the first site of recurrence.

After adjusting for these and other differences – including gender, age, histological subtype, mitotic rate, Clark level, and ulceration – the researchers observed no significant benefit for SNB vs. observation for melanoma-specific survival among patients in all thickness subgroups analyzed, he said.

Finally, in univariate analysis, early complete lymph node dissection failed to significantly improve distant metastases-free survival or melanoma-specific survival among SNB-positive patients of all thickness subgroups. There was a trend toward improved distant metastases free-survival favoring early vs. late dissection among patients with intermediate-thickness melanoma (P = .060).

"Our study suggests that patients with intermediate-thickness melanomas 1.2 [mm] to 3.5 [mm] are most likely to have therapeutic benefit from undergoing sentinel node biopsy," Mr. van der Ploeg concluded.

He added that the final results of the Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) are awaited with great interest, to better define melanoma patient subgroups most likely to obtain a survival benefit from SNB.

Interim analyses from MSLT-1 have confirmed that disease-free and distant disease-free survival are improved with SNB among patients with intermediate-thickness melanomas, but the long-running trial has failed to show a definitive overall survival advantage for the procedure.

During a discussion of the Australian study, audience members asked what techniques were used for SNB, remarking that the false-negative rate of 18% is well above the 4% rate reached by many groups today. Mr. van der Ploeg said the false-negative rate has fallen over time with more experience to 15%, and that surgeons use blue dye, but not the 10% rule during lymph node mapping.

The authors reported no disclosures.

SAN ANTONIO – In a large but nonrandomized group of patients with primary melanoma, sentinel node biopsy significantly prolonged disease-free survival, but offered no prolongation of distant metastases free- or melanoma-specific survival.

Researchers at the Melanoma Institute Australia in North Sydney evaluated survival among 5,567 patients who from 1992 to 2008 underwent wide local excision with or without sentinel node biopsy (SNB) for a primary melanoma that was at least 1 mm thick, Clark level IV or V, or had ulceration. Median follow-up was 3.5 years.

Among the 2,803 patients who underwent SNB, 390 had a positive sentinel node (14%), followed by early complete lymph node dissection. Of the 2,413 patients with a negative sentinel node, 88 experienced regional lymph node recurrence (3.6%) and underwent delayed total lymph node dissection. This resulted in a false-negative rate for SNB of 18.4%, Mr. Stijn van der Ploeg, M.Sc., reported.

Among the 2,765 patients who underwent wide local excision with nodal observation using ultrasound, 378 experienced regional lymph node recurrence (13.7%) and underwent delayed total lymph node dissection.

In univariate analysis, patients who underwent SNB had significantly improved disease-free survival and regional lymph node metastases-free survival (both P value less than .001), but no prolongation in distant metastases-free survival (P = .85) or melanoma-specific survival (P = .49), said Mr. van der Ploeg, now a doctoral student at Erasmus Medical Center in Rotterdam, The Netherlands.

When patients were stratified by tumor thickness, melanoma-specific survival significantly improved in SNB patients with tumors 1.2 mm to 3.5 mm thick (P = .01).

Mr. van der Ploeg pointed out that there were significant differences between the two groups. The SNB group had younger patients, more nodular melanomas, and more distant recurrence as the first site of recurrence, while the observation group had thinner primary tumors, more tumors located in the head and neck, and more nodal recurrences as the first site of recurrence.

After adjusting for these and other differences – including gender, age, histological subtype, mitotic rate, Clark level, and ulceration – the researchers observed no significant benefit for SNB vs. observation for melanoma-specific survival among patients in all thickness subgroups analyzed, he said.

Finally, in univariate analysis, early complete lymph node dissection failed to significantly improve distant metastases-free survival or melanoma-specific survival among SNB-positive patients of all thickness subgroups. There was a trend toward improved distant metastases free-survival favoring early vs. late dissection among patients with intermediate-thickness melanoma (P = .060).

"Our study suggests that patients with intermediate-thickness melanomas 1.2 [mm] to 3.5 [mm] are most likely to have therapeutic benefit from undergoing sentinel node biopsy," Mr. van der Ploeg concluded.

He added that the final results of the Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) are awaited with great interest, to better define melanoma patient subgroups most likely to obtain a survival benefit from SNB.

Interim analyses from MSLT-1 have confirmed that disease-free and distant disease-free survival are improved with SNB among patients with intermediate-thickness melanomas, but the long-running trial has failed to show a definitive overall survival advantage for the procedure.

During a discussion of the Australian study, audience members asked what techniques were used for SNB, remarking that the false-negative rate of 18% is well above the 4% rate reached by many groups today. Mr. van der Ploeg said the false-negative rate has fallen over time with more experience to 15%, and that surgeons use blue dye, but not the 10% rule during lymph node mapping.

The authors reported no disclosures.

SAN ANTONIO – In a large but nonrandomized group of patients with primary melanoma, sentinel node biopsy significantly prolonged disease-free survival, but offered no prolongation of distant metastases free- or melanoma-specific survival.

Researchers at the Melanoma Institute Australia in North Sydney evaluated survival among 5,567 patients who from 1992 to 2008 underwent wide local excision with or without sentinel node biopsy (SNB) for a primary melanoma that was at least 1 mm thick, Clark level IV or V, or had ulceration. Median follow-up was 3.5 years.

Among the 2,803 patients who underwent SNB, 390 had a positive sentinel node (14%), followed by early complete lymph node dissection. Of the 2,413 patients with a negative sentinel node, 88 experienced regional lymph node recurrence (3.6%) and underwent delayed total lymph node dissection. This resulted in a false-negative rate for SNB of 18.4%, Mr. Stijn van der Ploeg, M.Sc., reported.

Among the 2,765 patients who underwent wide local excision with nodal observation using ultrasound, 378 experienced regional lymph node recurrence (13.7%) and underwent delayed total lymph node dissection.

In univariate analysis, patients who underwent SNB had significantly improved disease-free survival and regional lymph node metastases-free survival (both P value less than .001), but no prolongation in distant metastases-free survival (P = .85) or melanoma-specific survival (P = .49), said Mr. van der Ploeg, now a doctoral student at Erasmus Medical Center in Rotterdam, The Netherlands.

When patients were stratified by tumor thickness, melanoma-specific survival significantly improved in SNB patients with tumors 1.2 mm to 3.5 mm thick (P = .01).

Mr. van der Ploeg pointed out that there were significant differences between the two groups. The SNB group had younger patients, more nodular melanomas, and more distant recurrence as the first site of recurrence, while the observation group had thinner primary tumors, more tumors located in the head and neck, and more nodal recurrences as the first site of recurrence.

After adjusting for these and other differences – including gender, age, histological subtype, mitotic rate, Clark level, and ulceration – the researchers observed no significant benefit for SNB vs. observation for melanoma-specific survival among patients in all thickness subgroups analyzed, he said.

Finally, in univariate analysis, early complete lymph node dissection failed to significantly improve distant metastases-free survival or melanoma-specific survival among SNB-positive patients of all thickness subgroups. There was a trend toward improved distant metastases free-survival favoring early vs. late dissection among patients with intermediate-thickness melanoma (P = .060).

"Our study suggests that patients with intermediate-thickness melanomas 1.2 [mm] to 3.5 [mm] are most likely to have therapeutic benefit from undergoing sentinel node biopsy," Mr. van der Ploeg concluded.

He added that the final results of the Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) are awaited with great interest, to better define melanoma patient subgroups most likely to obtain a survival benefit from SNB.

Interim analyses from MSLT-1 have confirmed that disease-free and distant disease-free survival are improved with SNB among patients with intermediate-thickness melanomas, but the long-running trial has failed to show a definitive overall survival advantage for the procedure.

During a discussion of the Australian study, audience members asked what techniques were used for SNB, remarking that the false-negative rate of 18% is well above the 4% rate reached by many groups today. Mr. van der Ploeg said the false-negative rate has fallen over time with more experience to 15%, and that surgeons use blue dye, but not the 10% rule during lymph node mapping.

The authors reported no disclosures.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data support coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported on April 4 at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG. The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years.

STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%). Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data support coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported on April 4 at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG. The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years.

STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%). Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data support coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported on April 4 at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG. The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years.

STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%). Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data support coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported on April 4 at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG. The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years.

STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%). Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data support coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported on April 4 at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG. The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years.

STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%). Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data support coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported on April 4 at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG. The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years.

STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%). Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data support coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported on April 4 at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG. The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years.

STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%). Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data support coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported on April 4 at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG. The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years.

STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%). Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data support coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported on April 4 at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG. The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years.

STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%). Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

NEW ORLEANS – Transcatheter aortic valve replacement was associated with the same survival rates at 1 year as was conventional surgery in older, high-risk patients with severe, symptomatic aortic stenosis in the PARTNER trial.

All-cause mortality at 30 days favored transcatheter aortic valve replacement (TAVR) at 3.4%, compared with 6.5% for open surgery, and was similar at 1 year (24% and 27%, respectively). The difference at 1 year reached the trial’s prespecified noninferiority margin with a P value of .001.

"We already learned from the previous cohort that TAVR is the standard of care for patients who can’t tolerate surgery. So this [finding] opens up a new set of patients who may very well benefit as much with TAVR as with the gold standard surgery," coprincipal investigator Dr. Craig B. Smith said at the annual meeting of the American College of Cardiology.

The stroke rate with TAVR in the industry-sponsored PARTNER (Placement of Aortic Transcatheter Valve) trial, however, was associated with a stroke rate that was twice the rate observed with surgery.

Stroke plus transient ischemic attack (TIA) rates were significantly more frequent with TAVR than surgery at both 30 days (5.5% vs. 2.4%) and 1 year (8.3% vs. 4.3%). When only major strokes were compared, the difference was not significant between TAVR and surgery at 30 days (3.8% vs. 2.1%) or 1 year (5.1% vs. 2.4%), said Dr. Smith, chief of cardiothoracic surgery at New York–Presbyterian Hospital/Columbia University Medical Center in New York City.

Notably, patients who underwent conventional surgery were significantly more likely than TAVR patients to experience major bleeding at 30 days (19.5% vs. 9.3%) and 1 year (26% vs. 15%), as well as new atrial fibrillation at both 30 days (16% vs. 8.6%) and 1 year (17% vs. 12%).

Echocardiographic findings indicated a small hemodynamic benefit with TAVR vs. surgery at 1 year, but significantly increased paravalvular aortic regurgitation at 30 days, 6 months, and 1 year.

"TAVR and AVR [aortic valve replacement] are both acceptable therapies in these high-risk patients; differing periprocedural hazards should influence case-based decision making," Dr. Smith said.

Dr. David Moliterno, chair of the intervention program (i2 Summit) at the meeting, told reporters that they were witnessing history in the making.

"This will probably be seen as one of the biggest steps in cardiovascular medicine, as far as intervention is concerned, potentially in our lifetime," said Dr. Moliterno, chief of cardiovascular medicine at the University of Kentucky, Lexington. "If we look back to balloon angioplasty, the advent of stents and drug-eluting stents, ... this will be seen as the next major turning point."

Last year, the PARTNER trial investigators reported a 20% survival benefit at 1 year in a separate cohort of 358 inoperable patients with severe aortic stenosis who underwent transfemoral TAVR vs. standard therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-607). TAVR was associated with significantly more major vascular complications (16% vs. 1%) and a higher incidence of major strokes (5% vs. 1%).

The current portion of PARTNER randomly assigned 699 patients at 26 centers to surgery or TAVR, using the transfemoral approach in 492 patients and the transapical approach in 207.

Severe stenosis was defined as an aortic valve area of less than 0.8 cm² and mean aortic valve gradient of more than 40 mm Hg or a peak aortic jet velocity of more than 4.0 m/second. The patients had a New York Heart Association heart failure class II or greater, and had a predicted risk of operative mortality of at least 15% as determined by the site surgeon and cardiologist, coupled with a Society of Thoracic Surgery score of at least 10.

Their mean age was 83 years, and 94% were NYHA class III or IV. In all, 42 patients were not treated as assigned, Dr. Smith said.

All-cause mortality at 1 year was similar for the transfemoral TAVR subgroup, at 22.2% and 26.4% for surgery, as well as for the transapical TAVR subgroup (29% vs. 28%, respectively).

A preliminary subgroup analysis suggests that there may be a possible benefit with TAVR in women and patients without prior coronary artery bypass surgery, but Dr. Smith said that those results should be interpreted cautiously.

Overall, the TAVR mortality of 3.4% at 30-days was the lowest reported in any series, despite the use of an early-generation device and limited previous operator experience, he said, noting that nine of the participating centers had never performed TAVR before the trial.

Symptom improvement, including NYHA class and 6-minute walk distance, favored TAVR at 30 days and was similar to conventional surgery at 1 year, he said.

Coinvestigator Dr. Murat Tuzcu, vice chair of the department of cardiovascular medicine at the Cleveland Clinic, stressed that the results were accomplished only through unprecedented teamwork among cardiologists, surgeons, and imaging experts, who consulted on each case in the trial.

"I want to emphasize that if we fail to pay equal attention to what we have done in this trial after the device is approved, I don’t think we will be able to replicate the same results," he said.

Several speakers at the press conference noted the balancing act that all clinicians will face regarding public demand for the new procedure.

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, observed that centers will face substantial up-front costs in the adoption of TAVR, including hybrid surgical/interventional suites, and that this will restrict initial uptake to high-volume centers of excellence.

The 3.4% mortality rate represents an "amazing effort," particularly in the use of the larger, first-generation device, said invited discussant Dr. Martyn Thomas, clinical director of cardiothoracic services at St. Thomas’ Hospital, London. The delivery catheters used in PARTNER are sized at 22 and 24 French, which corresponds to an outside diameter of 7-8 mm. The size of catheters is down to 16-Fr in Europe, where more than 5,000 TAVR procedures have been done and where both the Edwards Lifesciences Corp.’s Sapien valve that was used in PARTNER and the Medtronic Inc.’s CoreValve are already on the market.

Recruitment began in February for the PARTNER II trial that evaluated the smaller Edwards Sapien XT device and the later generation NovaFlex delivery system among inoperable patients with symptomatic severe aortic stenosis. The trial is expected to enroll 600 patients, and is targeted for primary completion in December 2011.

When asked whether the advent of newer, thinner devices will mean adoption in patients with lower risk, Dr. Smith replied that the adoption of TAVR will "march steadily down the risk categories."

Edwards Lifesciences sponsored the trial. Dr. Smith and his coauthors reported no conflicts of interest.

NEW ORLEANS – Transcatheter aortic valve replacement was associated with the same survival rates at 1 year as was conventional surgery in older, high-risk patients with severe, symptomatic aortic stenosis in the PARTNER trial.

All-cause mortality at 30 days favored transcatheter aortic valve replacement (TAVR) at 3.4%, compared with 6.5% for open surgery, and was similar at 1 year (24% and 27%, respectively). The difference at 1 year reached the trial’s prespecified noninferiority margin with a P value of .001.

"We already learned from the previous cohort that TAVR is the standard of care for patients who can’t tolerate surgery. So this [finding] opens up a new set of patients who may very well benefit as much with TAVR as with the gold standard surgery," coprincipal investigator Dr. Craig B. Smith said at the annual meeting of the American College of Cardiology.

The stroke rate with TAVR in the industry-sponsored PARTNER (Placement of Aortic Transcatheter Valve) trial, however, was associated with a stroke rate that was twice the rate observed with surgery.

Stroke plus transient ischemic attack (TIA) rates were significantly more frequent with TAVR than surgery at both 30 days (5.5% vs. 2.4%) and 1 year (8.3% vs. 4.3%). When only major strokes were compared, the difference was not significant between TAVR and surgery at 30 days (3.8% vs. 2.1%) or 1 year (5.1% vs. 2.4%), said Dr. Smith, chief of cardiothoracic surgery at New York–Presbyterian Hospital/Columbia University Medical Center in New York City.

Notably, patients who underwent conventional surgery were significantly more likely than TAVR patients to experience major bleeding at 30 days (19.5% vs. 9.3%) and 1 year (26% vs. 15%), as well as new atrial fibrillation at both 30 days (16% vs. 8.6%) and 1 year (17% vs. 12%).

Echocardiographic findings indicated a small hemodynamic benefit with TAVR vs. surgery at 1 year, but significantly increased paravalvular aortic regurgitation at 30 days, 6 months, and 1 year.

"TAVR and AVR [aortic valve replacement] are both acceptable therapies in these high-risk patients; differing periprocedural hazards should influence case-based decision making," Dr. Smith said.

Dr. David Moliterno, chair of the intervention program (i2 Summit) at the meeting, told reporters that they were witnessing history in the making.

"This will probably be seen as one of the biggest steps in cardiovascular medicine, as far as intervention is concerned, potentially in our lifetime," said Dr. Moliterno, chief of cardiovascular medicine at the University of Kentucky, Lexington. "If we look back to balloon angioplasty, the advent of stents and drug-eluting stents, ... this will be seen as the next major turning point."

Last year, the PARTNER trial investigators reported a 20% survival benefit at 1 year in a separate cohort of 358 inoperable patients with severe aortic stenosis who underwent transfemoral TAVR vs. standard therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-607). TAVR was associated with significantly more major vascular complications (16% vs. 1%) and a higher incidence of major strokes (5% vs. 1%).

The current portion of PARTNER randomly assigned 699 patients at 26 centers to surgery or TAVR, using the transfemoral approach in 492 patients and the transapical approach in 207.

Severe stenosis was defined as an aortic valve area of less than 0.8 cm² and mean aortic valve gradient of more than 40 mm Hg or a peak aortic jet velocity of more than 4.0 m/second. The patients had a New York Heart Association heart failure class II or greater, and had a predicted risk of operative mortality of at least 15% as determined by the site surgeon and cardiologist, coupled with a Society of Thoracic Surgery score of at least 10.

Their mean age was 83 years, and 94% were NYHA class III or IV. In all, 42 patients were not treated as assigned, Dr. Smith said.

All-cause mortality at 1 year was similar for the transfemoral TAVR subgroup, at 22.2% and 26.4% for surgery, as well as for the transapical TAVR subgroup (29% vs. 28%, respectively).

A preliminary subgroup analysis suggests that there may be a possible benefit with TAVR in women and patients without prior coronary artery bypass surgery, but Dr. Smith said that those results should be interpreted cautiously.

Overall, the TAVR mortality of 3.4% at 30-days was the lowest reported in any series, despite the use of an early-generation device and limited previous operator experience, he said, noting that nine of the participating centers had never performed TAVR before the trial.

Symptom improvement, including NYHA class and 6-minute walk distance, favored TAVR at 30 days and was similar to conventional surgery at 1 year, he said.

Coinvestigator Dr. Murat Tuzcu, vice chair of the department of cardiovascular medicine at the Cleveland Clinic, stressed that the results were accomplished only through unprecedented teamwork among cardiologists, surgeons, and imaging experts, who consulted on each case in the trial.

"I want to emphasize that if we fail to pay equal attention to what we have done in this trial after the device is approved, I don’t think we will be able to replicate the same results," he said.

Several speakers at the press conference noted the balancing act that all clinicians will face regarding public demand for the new procedure.

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, observed that centers will face substantial up-front costs in the adoption of TAVR, including hybrid surgical/interventional suites, and that this will restrict initial uptake to high-volume centers of excellence.

The 3.4% mortality rate represents an "amazing effort," particularly in the use of the larger, first-generation device, said invited discussant Dr. Martyn Thomas, clinical director of cardiothoracic services at St. Thomas’ Hospital, London. The delivery catheters used in PARTNER are sized at 22 and 24 French, which corresponds to an outside diameter of 7-8 mm. The size of catheters is down to 16-Fr in Europe, where more than 5,000 TAVR procedures have been done and where both the Edwards Lifesciences Corp.’s Sapien valve that was used in PARTNER and the Medtronic Inc.’s CoreValve are already on the market.

Recruitment began in February for the PARTNER II trial that evaluated the smaller Edwards Sapien XT device and the later generation NovaFlex delivery system among inoperable patients with symptomatic severe aortic stenosis. The trial is expected to enroll 600 patients, and is targeted for primary completion in December 2011.

When asked whether the advent of newer, thinner devices will mean adoption in patients with lower risk, Dr. Smith replied that the adoption of TAVR will "march steadily down the risk categories."

Edwards Lifesciences sponsored the trial. Dr. Smith and his coauthors reported no conflicts of interest.

NEW ORLEANS – Transcatheter aortic valve replacement was associated with the same survival rates at 1 year as was conventional surgery in older, high-risk patients with severe, symptomatic aortic stenosis in the PARTNER trial.

All-cause mortality at 30 days favored transcatheter aortic valve replacement (TAVR) at 3.4%, compared with 6.5% for open surgery, and was similar at 1 year (24% and 27%, respectively). The difference at 1 year reached the trial’s prespecified noninferiority margin with a P value of .001.

"We already learned from the previous cohort that TAVR is the standard of care for patients who can’t tolerate surgery. So this [finding] opens up a new set of patients who may very well benefit as much with TAVR as with the gold standard surgery," coprincipal investigator Dr. Craig B. Smith said at the annual meeting of the American College of Cardiology.

The stroke rate with TAVR in the industry-sponsored PARTNER (Placement of Aortic Transcatheter Valve) trial, however, was associated with a stroke rate that was twice the rate observed with surgery.

Stroke plus transient ischemic attack (TIA) rates were significantly more frequent with TAVR than surgery at both 30 days (5.5% vs. 2.4%) and 1 year (8.3% vs. 4.3%). When only major strokes were compared, the difference was not significant between TAVR and surgery at 30 days (3.8% vs. 2.1%) or 1 year (5.1% vs. 2.4%), said Dr. Smith, chief of cardiothoracic surgery at New York–Presbyterian Hospital/Columbia University Medical Center in New York City.

Notably, patients who underwent conventional surgery were significantly more likely than TAVR patients to experience major bleeding at 30 days (19.5% vs. 9.3%) and 1 year (26% vs. 15%), as well as new atrial fibrillation at both 30 days (16% vs. 8.6%) and 1 year (17% vs. 12%).

Echocardiographic findings indicated a small hemodynamic benefit with TAVR vs. surgery at 1 year, but significantly increased paravalvular aortic regurgitation at 30 days, 6 months, and 1 year.

"TAVR and AVR [aortic valve replacement] are both acceptable therapies in these high-risk patients; differing periprocedural hazards should influence case-based decision making," Dr. Smith said.

Dr. David Moliterno, chair of the intervention program (i2 Summit) at the meeting, told reporters that they were witnessing history in the making.

"This will probably be seen as one of the biggest steps in cardiovascular medicine, as far as intervention is concerned, potentially in our lifetime," said Dr. Moliterno, chief of cardiovascular medicine at the University of Kentucky, Lexington. "If we look back to balloon angioplasty, the advent of stents and drug-eluting stents, ... this will be seen as the next major turning point."

Last year, the PARTNER trial investigators reported a 20% survival benefit at 1 year in a separate cohort of 358 inoperable patients with severe aortic stenosis who underwent transfemoral TAVR vs. standard therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-607). TAVR was associated with significantly more major vascular complications (16% vs. 1%) and a higher incidence of major strokes (5% vs. 1%).

The current portion of PARTNER randomly assigned 699 patients at 26 centers to surgery or TAVR, using the transfemoral approach in 492 patients and the transapical approach in 207.

Severe stenosis was defined as an aortic valve area of less than 0.8 cm² and mean aortic valve gradient of more than 40 mm Hg or a peak aortic jet velocity of more than 4.0 m/second. The patients had a New York Heart Association heart failure class II or greater, and had a predicted risk of operative mortality of at least 15% as determined by the site surgeon and cardiologist, coupled with a Society of Thoracic Surgery score of at least 10.

Their mean age was 83 years, and 94% were NYHA class III or IV. In all, 42 patients were not treated as assigned, Dr. Smith said.

All-cause mortality at 1 year was similar for the transfemoral TAVR subgroup, at 22.2% and 26.4% for surgery, as well as for the transapical TAVR subgroup (29% vs. 28%, respectively).

A preliminary subgroup analysis suggests that there may be a possible benefit with TAVR in women and patients without prior coronary artery bypass surgery, but Dr. Smith said that those results should be interpreted cautiously.

Overall, the TAVR mortality of 3.4% at 30-days was the lowest reported in any series, despite the use of an early-generation device and limited previous operator experience, he said, noting that nine of the participating centers had never performed TAVR before the trial.

Symptom improvement, including NYHA class and 6-minute walk distance, favored TAVR at 30 days and was similar to conventional surgery at 1 year, he said.

Coinvestigator Dr. Murat Tuzcu, vice chair of the department of cardiovascular medicine at the Cleveland Clinic, stressed that the results were accomplished only through unprecedented teamwork among cardiologists, surgeons, and imaging experts, who consulted on each case in the trial.

"I want to emphasize that if we fail to pay equal attention to what we have done in this trial after the device is approved, I don’t think we will be able to replicate the same results," he said.

Several speakers at the press conference noted the balancing act that all clinicians will face regarding public demand for the new procedure.

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, observed that centers will face substantial up-front costs in the adoption of TAVR, including hybrid surgical/interventional suites, and that this will restrict initial uptake to high-volume centers of excellence.

The 3.4% mortality rate represents an "amazing effort," particularly in the use of the larger, first-generation device, said invited discussant Dr. Martyn Thomas, clinical director of cardiothoracic services at St. Thomas’ Hospital, London. The delivery catheters used in PARTNER are sized at 22 and 24 French, which corresponds to an outside diameter of 7-8 mm. The size of catheters is down to 16-Fr in Europe, where more than 5,000 TAVR procedures have been done and where both the Edwards Lifesciences Corp.’s Sapien valve that was used in PARTNER and the Medtronic Inc.’s CoreValve are already on the market.

Recruitment began in February for the PARTNER II trial that evaluated the smaller Edwards Sapien XT device and the later generation NovaFlex delivery system among inoperable patients with symptomatic severe aortic stenosis. The trial is expected to enroll 600 patients, and is targeted for primary completion in December 2011.

When asked whether the advent of newer, thinner devices will mean adoption in patients with lower risk, Dr. Smith replied that the adoption of TAVR will "march steadily down the risk categories."

Edwards Lifesciences sponsored the trial. Dr. Smith and his coauthors reported no conflicts of interest.

NEW ORLEANS – Transcatheter aortic valve replacement was associated with the same survival rates at 1 year as was conventional surgery in older, high-risk patients with severe, symptomatic aortic stenosis in the PARTNER trial.

All-cause mortality at 30 days favored transcatheter aortic valve replacement (TAVR) at 3.4%, compared with 6.5% for open surgery, and was similar at 1 year (24% and 27%, respectively). The difference at 1 year reached the trial’s prespecified noninferiority margin with a P value of .001.

"We already learned from the previous cohort that TAVR is the standard of care for patients who can’t tolerate surgery. So this [finding] opens up a new set of patients who may very well benefit as much with TAVR as with the gold standard surgery," coprincipal investigator Dr. Craig B. Smith said at the annual meeting of the American College of Cardiology.

The stroke rate with TAVR in the industry-sponsored PARTNER (Placement of Aortic Transcatheter Valve) trial, however, was associated with a stroke rate that was twice the rate observed with surgery.

Stroke plus transient ischemic attack (TIA) rates were significantly more frequent with TAVR than surgery at both 30 days (5.5% vs. 2.4%) and 1 year (8.3% vs. 4.3%). When only major strokes were compared, the difference was not significant between TAVR and surgery at 30 days (3.8% vs. 2.1%) or 1 year (5.1% vs. 2.4%), said Dr. Smith, chief of cardiothoracic surgery at New York–Presbyterian Hospital/Columbia University Medical Center in New York City.

Notably, patients who underwent conventional surgery were significantly more likely than TAVR patients to experience major bleeding at 30 days (19.5% vs. 9.3%) and 1 year (26% vs. 15%), as well as new atrial fibrillation at both 30 days (16% vs. 8.6%) and 1 year (17% vs. 12%).

Echocardiographic findings indicated a small hemodynamic benefit with TAVR vs. surgery at 1 year, but significantly increased paravalvular aortic regurgitation at 30 days, 6 months, and 1 year.

"TAVR and AVR [aortic valve replacement] are both acceptable therapies in these high-risk patients; differing periprocedural hazards should influence case-based decision making," Dr. Smith said.

Dr. David Moliterno, chair of the intervention program (i2 Summit) at the meeting, told reporters that they were witnessing history in the making.

"This will probably be seen as one of the biggest steps in cardiovascular medicine, as far as intervention is concerned, potentially in our lifetime," said Dr. Moliterno, chief of cardiovascular medicine at the University of Kentucky, Lexington. "If we look back to balloon angioplasty, the advent of stents and drug-eluting stents, ... this will be seen as the next major turning point."

Last year, the PARTNER trial investigators reported a 20% survival benefit at 1 year in a separate cohort of 358 inoperable patients with severe aortic stenosis who underwent transfemoral TAVR vs. standard therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-607). TAVR was associated with significantly more major vascular complications (16% vs. 1%) and a higher incidence of major strokes (5% vs. 1%).

The current portion of PARTNER randomly assigned 699 patients at 26 centers to surgery or TAVR, using the transfemoral approach in 492 patients and the transapical approach in 207.

Severe stenosis was defined as an aortic valve area of less than 0.8 cm² and mean aortic valve gradient of more than 40 mm Hg or a peak aortic jet velocity of more than 4.0 m/second. The patients had a New York Heart Association heart failure class II or greater, and had a predicted risk of operative mortality of at least 15% as determined by the site surgeon and cardiologist, coupled with a Society of Thoracic Surgery score of at least 10.

Their mean age was 83 years, and 94% were NYHA class III or IV. In all, 42 patients were not treated as assigned, Dr. Smith said.

All-cause mortality at 1 year was similar for the transfemoral TAVR subgroup, at 22.2% and 26.4% for surgery, as well as for the transapical TAVR subgroup (29% vs. 28%, respectively).

A preliminary subgroup analysis suggests that there may be a possible benefit with TAVR in women and patients without prior coronary artery bypass surgery, but Dr. Smith said that those results should be interpreted cautiously.

Overall, the TAVR mortality of 3.4% at 30-days was the lowest reported in any series, despite the use of an early-generation device and limited previous operator experience, he said, noting that nine of the participating centers had never performed TAVR before the trial.

Symptom improvement, including NYHA class and 6-minute walk distance, favored TAVR at 30 days and was similar to conventional surgery at 1 year, he said.

Coinvestigator Dr. Murat Tuzcu, vice chair of the department of cardiovascular medicine at the Cleveland Clinic, stressed that the results were accomplished only through unprecedented teamwork among cardiologists, surgeons, and imaging experts, who consulted on each case in the trial.

"I want to emphasize that if we fail to pay equal attention to what we have done in this trial after the device is approved, I don’t think we will be able to replicate the same results," he said.

Several speakers at the press conference noted the balancing act that all clinicians will face regarding public demand for the new procedure.

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, observed that centers will face substantial up-front costs in the adoption of TAVR, including hybrid surgical/interventional suites, and that this will restrict initial uptake to high-volume centers of excellence.

The 3.4% mortality rate represents an "amazing effort," particularly in the use of the larger, first-generation device, said invited discussant Dr. Martyn Thomas, clinical director of cardiothoracic services at St. Thomas’ Hospital, London. The delivery catheters used in PARTNER are sized at 22 and 24 French, which corresponds to an outside diameter of 7-8 mm. The size of catheters is down to 16-Fr in Europe, where more than 5,000 TAVR procedures have been done and where both the Edwards Lifesciences Corp.’s Sapien valve that was used in PARTNER and the Medtronic Inc.’s CoreValve are already on the market.

Recruitment began in February for the PARTNER II trial that evaluated the smaller Edwards Sapien XT device and the later generation NovaFlex delivery system among inoperable patients with symptomatic severe aortic stenosis. The trial is expected to enroll 600 patients, and is targeted for primary completion in December 2011.

When asked whether the advent of newer, thinner devices will mean adoption in patients with lower risk, Dr. Smith replied that the adoption of TAVR will "march steadily down the risk categories."

Edwards Lifesciences sponsored the trial. Dr. Smith and his coauthors reported no conflicts of interest.

NEW ORLEANS – Transcatheter aortic valve replacement was associated with the same survival rates at 1 year as was conventional surgery in older, high-risk patients with severe, symptomatic aortic stenosis in the PARTNER trial.

All-cause mortality at 30 days favored transcatheter aortic valve replacement (TAVR) at 3.4%, compared with 6.5% for open surgery, and was similar at 1 year (24% and 27%, respectively). The difference at 1 year reached the trial’s prespecified noninferiority margin with a P value of .001.

"We already learned from the previous cohort that TAVR is the standard of care for patients who can’t tolerate surgery. So this [finding] opens up a new set of patients who may very well benefit as much with TAVR as with the gold standard surgery," coprincipal investigator Dr. Craig B. Smith said at the annual meeting of the American College of Cardiology.

The stroke rate with TAVR in the industry-sponsored PARTNER (Placement of Aortic Transcatheter Valve) trial, however, was associated with a stroke rate that was twice the rate observed with surgery.

Stroke plus transient ischemic attack (TIA) rates were significantly more frequent with TAVR than surgery at both 30 days (5.5% vs. 2.4%) and 1 year (8.3% vs. 4.3%). When only major strokes were compared, the difference was not significant between TAVR and surgery at 30 days (3.8% vs. 2.1%) or 1 year (5.1% vs. 2.4%), said Dr. Smith, chief of cardiothoracic surgery at New York–Presbyterian Hospital/Columbia University Medical Center in New York City.

Notably, patients who underwent conventional surgery were significantly more likely than TAVR patients to experience major bleeding at 30 days (19.5% vs. 9.3%) and 1 year (26% vs. 15%), as well as new atrial fibrillation at both 30 days (16% vs. 8.6%) and 1 year (17% vs. 12%).

Echocardiographic findings indicated a small hemodynamic benefit with TAVR vs. surgery at 1 year, but significantly increased paravalvular aortic regurgitation at 30 days, 6 months, and 1 year.

"TAVR and AVR [aortic valve replacement] are both acceptable therapies in these high-risk patients; differing periprocedural hazards should influence case-based decision making," Dr. Smith said.

Dr. David Moliterno, chair of the intervention program (i2 Summit) at the meeting, told reporters that they were witnessing history in the making.

"This will probably be seen as one of the biggest steps in cardiovascular medicine, as far as intervention is concerned, potentially in our lifetime," said Dr. Moliterno, chief of cardiovascular medicine at the University of Kentucky, Lexington. "If we look back to balloon angioplasty, the advent of stents and drug-eluting stents, ... this will be seen as the next major turning point."

Last year, the PARTNER trial investigators reported a 20% survival benefit at 1 year in a separate cohort of 358 inoperable patients with severe aortic stenosis who underwent transfemoral TAVR vs. standard therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-607). TAVR was associated with significantly more major vascular complications (16% vs. 1%) and a higher incidence of major strokes (5% vs. 1%).

The current portion of PARTNER randomly assigned 699 patients at 26 centers to surgery or TAVR, using the transfemoral approach in 492 patients and the transapical approach in 207.

Severe stenosis was defined as an aortic valve area of less than 0.8 cm² and mean aortic valve gradient of more than 40 mm Hg or a peak aortic jet velocity of more than 4.0 m/second. The patients had a New York Heart Association heart failure class II or greater, and had a predicted risk of operative mortality of at least 15% as determined by the site surgeon and cardiologist, coupled with a Society of Thoracic Surgery score of at least 10.

Their mean age was 83 years, and 94% were NYHA class III or IV. In all, 42 patients were not treated as assigned, Dr. Smith said.

All-cause mortality at 1 year was similar for the transfemoral TAVR subgroup, at 22.2% and 26.4% for surgery, as well as for the transapical TAVR subgroup (29% vs. 28%, respectively).

A preliminary subgroup analysis suggests that there may be a possible benefit with TAVR in women and patients without prior coronary artery bypass surgery, but Dr. Smith said that those results should be interpreted cautiously.

Overall, the TAVR mortality of 3.4% at 30-days was the lowest reported in any series, despite the use of an early-generation device and limited previous operator experience, he said, noting that nine of the participating centers had never performed TAVR before the trial.

Symptom improvement, including NYHA class and 6-minute walk distance, favored TAVR at 30 days and was similar to conventional surgery at 1 year, he said.

Coinvestigator Dr. Murat Tuzcu, vice chair of the department of cardiovascular medicine at the Cleveland Clinic, stressed that the results were accomplished only through unprecedented teamwork among cardiologists, surgeons, and imaging experts, who consulted on each case in the trial.

"I want to emphasize that if we fail to pay equal attention to what we have done in this trial after the device is approved, I don’t think we will be able to replicate the same results," he said.

Several speakers at the press conference noted the balancing act that all clinicians will face regarding public demand for the new procedure.

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, observed that centers will face substantial up-front costs in the adoption of TAVR, including hybrid surgical/interventional suites, and that this will restrict initial uptake to high-volume centers of excellence.

The 3.4% mortality rate represents an "amazing effort," particularly in the use of the larger, first-generation device, said invited discussant Dr. Martyn Thomas, clinical director of cardiothoracic services at St. Thomas’ Hospital, London. The delivery catheters used in PARTNER are sized at 22 and 24 French, which corresponds to an outside diameter of 7-8 mm. The size of catheters is down to 16-Fr in Europe, where more than 5,000 TAVR procedures have been done and where both the Edwards Lifesciences Corp.’s Sapien valve that was used in PARTNER and the Medtronic Inc.’s CoreValve are already on the market.

Recruitment began in February for the PARTNER II trial that evaluated the smaller Edwards Sapien XT device and the later generation NovaFlex delivery system among inoperable patients with symptomatic severe aortic stenosis. The trial is expected to enroll 600 patients, and is targeted for primary completion in December 2011.

When asked whether the advent of newer, thinner devices will mean adoption in patients with lower risk, Dr. Smith replied that the adoption of TAVR will "march steadily down the risk categories."

Edwards Lifesciences sponsored the trial. Dr. Smith and his coauthors reported no conflicts of interest.

NEW ORLEANS – Transcatheter aortic valve replacement was associated with the same survival rates at 1 year as was conventional surgery in older, high-risk patients with severe, symptomatic aortic stenosis in the PARTNER trial.

All-cause mortality at 30 days favored transcatheter aortic valve replacement (TAVR) at 3.4%, compared with 6.5% for open surgery, and was similar at 1 year (24% and 27%, respectively). The difference at 1 year reached the trial’s prespecified noninferiority margin with a P value of .001.

"We already learned from the previous cohort that TAVR is the standard of care for patients who can’t tolerate surgery. So this [finding] opens up a new set of patients who may very well benefit as much with TAVR as with the gold standard surgery," coprincipal investigator Dr. Craig B. Smith said at the annual meeting of the American College of Cardiology.

The stroke rate with TAVR in the industry-sponsored PARTNER (Placement of Aortic Transcatheter Valve) trial, however, was associated with a stroke rate that was twice the rate observed with surgery.

Stroke plus transient ischemic attack (TIA) rates were significantly more frequent with TAVR than surgery at both 30 days (5.5% vs. 2.4%) and 1 year (8.3% vs. 4.3%). When only major strokes were compared, the difference was not significant between TAVR and surgery at 30 days (3.8% vs. 2.1%) or 1 year (5.1% vs. 2.4%), said Dr. Smith, chief of cardiothoracic surgery at New York–Presbyterian Hospital/Columbia University Medical Center in New York City.

Notably, patients who underwent conventional surgery were significantly more likely than TAVR patients to experience major bleeding at 30 days (19.5% vs. 9.3%) and 1 year (26% vs. 15%), as well as new atrial fibrillation at both 30 days (16% vs. 8.6%) and 1 year (17% vs. 12%).

Echocardiographic findings indicated a small hemodynamic benefit with TAVR vs. surgery at 1 year, but significantly increased paravalvular aortic regurgitation at 30 days, 6 months, and 1 year.

"TAVR and AVR [aortic valve replacement] are both acceptable therapies in these high-risk patients; differing periprocedural hazards should influence case-based decision making," Dr. Smith said.

Dr. David Moliterno, chair of the intervention program (i2 Summit) at the meeting, told reporters that they were witnessing history in the making.

"This will probably be seen as one of the biggest steps in cardiovascular medicine, as far as intervention is concerned, potentially in our lifetime," said Dr. Moliterno, chief of cardiovascular medicine at the University of Kentucky, Lexington. "If we look back to balloon angioplasty, the advent of stents and drug-eluting stents, ... this will be seen as the next major turning point."

Last year, the PARTNER trial investigators reported a 20% survival benefit at 1 year in a separate cohort of 358 inoperable patients with severe aortic stenosis who underwent transfemoral TAVR vs. standard therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-607). TAVR was associated with significantly more major vascular complications (16% vs. 1%) and a higher incidence of major strokes (5% vs. 1%).

The current portion of PARTNER randomly assigned 699 patients at 26 centers to surgery or TAVR, using the transfemoral approach in 492 patients and the transapical approach in 207.

Severe stenosis was defined as an aortic valve area of less than 0.8 cm² and mean aortic valve gradient of more than 40 mm Hg or a peak aortic jet velocity of more than 4.0 m/second. The patients had a New York Heart Association heart failure class II or greater, and had a predicted risk of operative mortality of at least 15% as determined by the site surgeon and cardiologist, coupled with a Society of Thoracic Surgery score of at least 10.

Their mean age was 83 years, and 94% were NYHA class III or IV. In all, 42 patients were not treated as assigned, Dr. Smith said.

All-cause mortality at 1 year was similar for the transfemoral TAVR subgroup, at 22.2% and 26.4% for surgery, as well as for the transapical TAVR subgroup (29% vs. 28%, respectively).

A preliminary subgroup analysis suggests that there may be a possible benefit with TAVR in women and patients without prior coronary artery bypass surgery, but Dr. Smith said that those results should be interpreted cautiously.

Overall, the TAVR mortality of 3.4% at 30-days was the lowest reported in any series, despite the use of an early-generation device and limited previous operator experience, he said, noting that nine of the participating centers had never performed TAVR before the trial.

Symptom improvement, including NYHA class and 6-minute walk distance, favored TAVR at 30 days and was similar to conventional surgery at 1 year, he said.

Coinvestigator Dr. Murat Tuzcu, vice chair of the department of cardiovascular medicine at the Cleveland Clinic, stressed that the results were accomplished only through unprecedented teamwork among cardiologists, surgeons, and imaging experts, who consulted on each case in the trial.

"I want to emphasize that if we fail to pay equal attention to what we have done in this trial after the device is approved, I don’t think we will be able to replicate the same results," he said.

Several speakers at the press conference noted the balancing act that all clinicians will face regarding public demand for the new procedure.

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, observed that centers will face substantial up-front costs in the adoption of TAVR, including hybrid surgical/interventional suites, and that this will restrict initial uptake to high-volume centers of excellence.

The 3.4% mortality rate represents an "amazing effort," particularly in the use of the larger, first-generation device, said invited discussant Dr. Martyn Thomas, clinical director of cardiothoracic services at St. Thomas’ Hospital, London. The delivery catheters used in PARTNER are sized at 22 and 24 French, which corresponds to an outside diameter of 7-8 mm. The size of catheters is down to 16-Fr in Europe, where more than 5,000 TAVR procedures have been done and where both the Edwards Lifesciences Corp.’s Sapien valve that was used in PARTNER and the Medtronic Inc.’s CoreValve are already on the market.

Recruitment began in February for the PARTNER II trial that evaluated the smaller Edwards Sapien XT device and the later generation NovaFlex delivery system among inoperable patients with symptomatic severe aortic stenosis. The trial is expected to enroll 600 patients, and is targeted for primary completion in December 2011.

When asked whether the advent of newer, thinner devices will mean adoption in patients with lower risk, Dr. Smith replied that the adoption of TAVR will "march steadily down the risk categories."

Edwards Lifesciences sponsored the trial. Dr. Smith and his coauthors reported no conflicts of interest.

NEW ORLEANS – Transcatheter aortic valve replacement was associated with the same survival rates at 1 year as was conventional surgery in older, high-risk patients with severe, symptomatic aortic stenosis in the PARTNER trial.

All-cause mortality at 30 days favored transcatheter aortic valve replacement (TAVR) at 3.4%, compared with 6.5% for open surgery, and was similar at 1 year (24% and 27%, respectively). The difference at 1 year reached the trial’s prespecified noninferiority margin with a P value of .001.

"We already learned from the previous cohort that TAVR is the standard of care for patients who can’t tolerate surgery. So this [finding] opens up a new set of patients who may very well benefit as much with TAVR as with the gold standard surgery," coprincipal investigator Dr. Craig B. Smith said at the annual meeting of the American College of Cardiology.

The stroke rate with TAVR in the industry-sponsored PARTNER (Placement of Aortic Transcatheter Valve) trial, however, was associated with a stroke rate that was twice the rate observed with surgery.

Stroke plus transient ischemic attack (TIA) rates were significantly more frequent with TAVR than surgery at both 30 days (5.5% vs. 2.4%) and 1 year (8.3% vs. 4.3%). When only major strokes were compared, the difference was not significant between TAVR and surgery at 30 days (3.8% vs. 2.1%) or 1 year (5.1% vs. 2.4%), said Dr. Smith, chief of cardiothoracic surgery at New York–Presbyterian Hospital/Columbia University Medical Center in New York City.

Notably, patients who underwent conventional surgery were significantly more likely than TAVR patients to experience major bleeding at 30 days (19.5% vs. 9.3%) and 1 year (26% vs. 15%), as well as new atrial fibrillation at both 30 days (16% vs. 8.6%) and 1 year (17% vs. 12%).

Echocardiographic findings indicated a small hemodynamic benefit with TAVR vs. surgery at 1 year, but significantly increased paravalvular aortic regurgitation at 30 days, 6 months, and 1 year.

"TAVR and AVR [aortic valve replacement] are both acceptable therapies in these high-risk patients; differing periprocedural hazards should influence case-based decision making," Dr. Smith said.

Dr. David Moliterno, chair of the intervention program (i2 Summit) at the meeting, told reporters that they were witnessing history in the making.

"This will probably be seen as one of the biggest steps in cardiovascular medicine, as far as intervention is concerned, potentially in our lifetime," said Dr. Moliterno, chief of cardiovascular medicine at the University of Kentucky, Lexington. "If we look back to balloon angioplasty, the advent of stents and drug-eluting stents, ... this will be seen as the next major turning point."

Last year, the PARTNER trial investigators reported a 20% survival benefit at 1 year in a separate cohort of 358 inoperable patients with severe aortic stenosis who underwent transfemoral TAVR vs. standard therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-607). TAVR was associated with significantly more major vascular complications (16% vs. 1%) and a higher incidence of major strokes (5% vs. 1%).

The current portion of PARTNER randomly assigned 699 patients at 26 centers to surgery or TAVR, using the transfemoral approach in 492 patients and the transapical approach in 207.

Severe stenosis was defined as an aortic valve area of less than 0.8 cm² and mean aortic valve gradient of more than 40 mm Hg or a peak aortic jet velocity of more than 4.0 m/second. The patients had a New York Heart Association heart failure class II or greater, and had a predicted risk of operative mortality of at least 15% as determined by the site surgeon and cardiologist, coupled with a Society of Thoracic Surgery score of at least 10.

Their mean age was 83 years, and 94% were NYHA class III or IV. In all, 42 patients were not treated as assigned, Dr. Smith said.

All-cause mortality at 1 year was similar for the transfemoral TAVR subgroup, at 22.2% and 26.4% for surgery, as well as for the transapical TAVR subgroup (29% vs. 28%, respectively).

A preliminary subgroup analysis suggests that there may be a possible benefit with TAVR in women and patients without prior coronary artery bypass surgery, but Dr. Smith said that those results should be interpreted cautiously.

Overall, the TAVR mortality of 3.4% at 30-days was the lowest reported in any series, despite the use of an early-generation device and limited previous operator experience, he said, noting that nine of the participating centers had never performed TAVR before the trial.

Symptom improvement, including NYHA class and 6-minute walk distance, favored TAVR at 30 days and was similar to conventional surgery at 1 year, he said.

Coinvestigator Dr. Murat Tuzcu, vice chair of the department of cardiovascular medicine at the Cleveland Clinic, stressed that the results were accomplished only through unprecedented teamwork among cardiologists, surgeons, and imaging experts, who consulted on each case in the trial.

"I want to emphasize that if we fail to pay equal attention to what we have done in this trial after the device is approved, I don’t think we will be able to replicate the same results," he said.

Several speakers at the press conference noted the balancing act that all clinicians will face regarding public demand for the new procedure.

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, observed that centers will face substantial up-front costs in the adoption of TAVR, including hybrid surgical/interventional suites, and that this will restrict initial uptake to high-volume centers of excellence.

The 3.4% mortality rate represents an "amazing effort," particularly in the use of the larger, first-generation device, said invited discussant Dr. Martyn Thomas, clinical director of cardiothoracic services at St. Thomas’ Hospital, London. The delivery catheters used in PARTNER are sized at 22 and 24 French, which corresponds to an outside diameter of 7-8 mm. The size of catheters is down to 16-Fr in Europe, where more than 5,000 TAVR procedures have been done and where both the Edwards Lifesciences Corp.’s Sapien valve that was used in PARTNER and the Medtronic Inc.’s CoreValve are already on the market.

Recruitment began in February for the PARTNER II trial that evaluated the smaller Edwards Sapien XT device and the later generation NovaFlex delivery system among inoperable patients with symptomatic severe aortic stenosis. The trial is expected to enroll 600 patients, and is targeted for primary completion in December 2011.

When asked whether the advent of newer, thinner devices will mean adoption in patients with lower risk, Dr. Smith replied that the adoption of TAVR will "march steadily down the risk categories."

Edwards Lifesciences sponsored the trial. Dr. Smith and his coauthors reported no conflicts of interest.

NEW ORLEANS – Transcatheter aortic valve replacement was associated with the same survival rates at 1 year as was conventional surgery in older, high-risk patients with severe, symptomatic aortic stenosis in the PARTNER trial.

All-cause mortality at 30 days favored transcatheter aortic valve replacement (TAVR) at 3.4%, compared with 6.5% for open surgery, and was similar at 1 year (24% and 27%, respectively). The difference at 1 year reached the trial’s prespecified noninferiority margin with a P value of .001.

"We already learned from the previous cohort that TAVR is the standard of care for patients who can’t tolerate surgery. So this [finding] opens up a new set of patients who may very well benefit as much with TAVR as with the gold standard surgery," coprincipal investigator Dr. Craig B. Smith said at the annual meeting of the American College of Cardiology.

The stroke rate with TAVR in the industry-sponsored PARTNER (Placement of Aortic Transcatheter Valve) trial, however, was associated with a stroke rate that was twice the rate observed with surgery.

Stroke plus transient ischemic attack (TIA) rates were significantly more frequent with TAVR than surgery at both 30 days (5.5% vs. 2.4%) and 1 year (8.3% vs. 4.3%). When only major strokes were compared, the difference was not significant between TAVR and surgery at 30 days (3.8% vs. 2.1%) or 1 year (5.1% vs. 2.4%), said Dr. Smith, chief of cardiothoracic surgery at New York–Presbyterian Hospital/Columbia University Medical Center in New York City.

Notably, patients who underwent conventional surgery were significantly more likely than TAVR patients to experience major bleeding at 30 days (19.5% vs. 9.3%) and 1 year (26% vs. 15%), as well as new atrial fibrillation at both 30 days (16% vs. 8.6%) and 1 year (17% vs. 12%).

Echocardiographic findings indicated a small hemodynamic benefit with TAVR vs. surgery at 1 year, but significantly increased paravalvular aortic regurgitation at 30 days, 6 months, and 1 year.

"TAVR and AVR [aortic valve replacement] are both acceptable therapies in these high-risk patients; differing periprocedural hazards should influence case-based decision making," Dr. Smith said.

Dr. David Moliterno, chair of the intervention program (i2 Summit) at the meeting, told reporters that they were witnessing history in the making.

"This will probably be seen as one of the biggest steps in cardiovascular medicine, as far as intervention is concerned, potentially in our lifetime," said Dr. Moliterno, chief of cardiovascular medicine at the University of Kentucky, Lexington. "If we look back to balloon angioplasty, the advent of stents and drug-eluting stents, ... this will be seen as the next major turning point."

Last year, the PARTNER trial investigators reported a 20% survival benefit at 1 year in a separate cohort of 358 inoperable patients with severe aortic stenosis who underwent transfemoral TAVR vs. standard therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-607). TAVR was associated with significantly more major vascular complications (16% vs. 1%) and a higher incidence of major strokes (5% vs. 1%).

The current portion of PARTNER randomly assigned 699 patients at 26 centers to surgery or TAVR, using the transfemoral approach in 492 patients and the transapical approach in 207.

Severe stenosis was defined as an aortic valve area of less than 0.8 cm² and mean aortic valve gradient of more than 40 mm Hg or a peak aortic jet velocity of more than 4.0 m/second. The patients had a New York Heart Association heart failure class II or greater, and had a predicted risk of operative mortality of at least 15% as determined by the site surgeon and cardiologist, coupled with a Society of Thoracic Surgery score of at least 10.

Their mean age was 83 years, and 94% were NYHA class III or IV. In all, 42 patients were not treated as assigned, Dr. Smith said.

All-cause mortality at 1 year was similar for the transfemoral TAVR subgroup, at 22.2% and 26.4% for surgery, as well as for the transapical TAVR subgroup (29% vs. 28%, respectively).

A preliminary subgroup analysis suggests that there may be a possible benefit with TAVR in women and patients without prior coronary artery bypass surgery, but Dr. Smith said that those results should be interpreted cautiously.

Overall, the TAVR mortality of 3.4% at 30-days was the lowest reported in any series, despite the use of an early-generation device and limited previous operator experience, he said, noting that nine of the participating centers had never performed TAVR before the trial.

Symptom improvement, including NYHA class and 6-minute walk distance, favored TAVR at 30 days and was similar to conventional surgery at 1 year, he said.

Coinvestigator Dr. Murat Tuzcu, vice chair of the department of cardiovascular medicine at the Cleveland Clinic, stressed that the results were accomplished only through unprecedented teamwork among cardiologists, surgeons, and imaging experts, who consulted on each case in the trial.

"I want to emphasize that if we fail to pay equal attention to what we have done in this trial after the device is approved, I don’t think we will be able to replicate the same results," he said.

Several speakers at the press conference noted the balancing act that all clinicians will face regarding public demand for the new procedure.

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, observed that centers will face substantial up-front costs in the adoption of TAVR, including hybrid surgical/interventional suites, and that this will restrict initial uptake to high-volume centers of excellence.

The 3.4% mortality rate represents an "amazing effort," particularly in the use of the larger, first-generation device, said invited discussant Dr. Martyn Thomas, clinical director of cardiothoracic services at St. Thomas’ Hospital, London. The delivery catheters used in PARTNER are sized at 22 and 24 French, which corresponds to an outside diameter of 7-8 mm. The size of catheters is down to 16-Fr in Europe, where more than 5,000 TAVR procedures have been done and where both the Edwards Lifesciences Corp.’s Sapien valve that was used in PARTNER and the Medtronic Inc.’s CoreValve are already on the market.

Recruitment began in February for the PARTNER II trial that evaluated the smaller Edwards Sapien XT device and the later generation NovaFlex delivery system among inoperable patients with symptomatic severe aortic stenosis. The trial is expected to enroll 600 patients, and is targeted for primary completion in December 2011.

When asked whether the advent of newer, thinner devices will mean adoption in patients with lower risk, Dr. Smith replied that the adoption of TAVR will "march steadily down the risk categories."

Edwards Lifesciences sponsored the trial. Dr. Smith and his coauthors reported no conflicts of interest.

NEW ORLEANS – Transcatheter aortic valve replacement was associated with the same survival rates at 1 year as was conventional surgery in older, high-risk patients with severe, symptomatic aortic stenosis in the PARTNER trial.

All-cause mortality at 30 days favored transcatheter aortic valve replacement (TAVR) at 3.4%, compared with 6.5% for open surgery, and was similar at 1 year (24% and 27%, respectively). The difference at 1 year reached the trial’s prespecified noninferiority margin with a P value of .001.

"We already learned from the previous cohort that TAVR is the standard of care for patients who can’t tolerate surgery. So this [finding] opens up a new set of patients who may very well benefit as much with TAVR as with the gold standard surgery," coprincipal investigator Dr. Craig B. Smith said at the annual meeting of the American College of Cardiology.

The stroke rate with TAVR in the industry-sponsored PARTNER (Placement of Aortic Transcatheter Valve) trial, however, was associated with a stroke rate that was twice the rate observed with surgery.

Stroke plus transient ischemic attack (TIA) rates were significantly more frequent with TAVR than surgery at both 30 days (5.5% vs. 2.4%) and 1 year (8.3% vs. 4.3%). When only major strokes were compared, the difference was not significant between TAVR and surgery at 30 days (3.8% vs. 2.1%) or 1 year (5.1% vs. 2.4%), said Dr. Smith, chief of cardiothoracic surgery at New York–Presbyterian Hospital/Columbia University Medical Center in New York City.

Notably, patients who underwent conventional surgery were significantly more likely than TAVR patients to experience major bleeding at 30 days (19.5% vs. 9.3%) and 1 year (26% vs. 15%), as well as new atrial fibrillation at both 30 days (16% vs. 8.6%) and 1 year (17% vs. 12%).

Echocardiographic findings indicated a small hemodynamic benefit with TAVR vs. surgery at 1 year, but significantly increased paravalvular aortic regurgitation at 30 days, 6 months, and 1 year.

"TAVR and AVR [aortic valve replacement] are both acceptable therapies in these high-risk patients; differing periprocedural hazards should influence case-based decision making," Dr. Smith said.

Dr. David Moliterno, chair of the intervention program (i2 Summit) at the meeting, told reporters that they were witnessing history in the making.

"This will probably be seen as one of the biggest steps in cardiovascular medicine, as far as intervention is concerned, potentially in our lifetime," said Dr. Moliterno, chief of cardiovascular medicine at the University of Kentucky, Lexington. "If we look back to balloon angioplasty, the advent of stents and drug-eluting stents, ... this will be seen as the next major turning point."

Last year, the PARTNER trial investigators reported a 20% survival benefit at 1 year in a separate cohort of 358 inoperable patients with severe aortic stenosis who underwent transfemoral TAVR vs. standard therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-607). TAVR was associated with significantly more major vascular complications (16% vs. 1%) and a higher incidence of major strokes (5% vs. 1%).

The current portion of PARTNER randomly assigned 699 patients at 26 centers to surgery or TAVR, using the transfemoral approach in 492 patients and the transapical approach in 207.

Severe stenosis was defined as an aortic valve area of less than 0.8 cm² and mean aortic valve gradient of more than 40 mm Hg or a peak aortic jet velocity of more than 4.0 m/second. The patients had a New York Heart Association heart failure class II or greater, and had a predicted risk of operative mortality of at least 15% as determined by the site surgeon and cardiologist, coupled with a Society of Thoracic Surgery score of at least 10.

Their mean age was 83 years, and 94% were NYHA class III or IV. In all, 42 patients were not treated as assigned, Dr. Smith said.

All-cause mortality at 1 year was similar for the transfemoral TAVR subgroup, at 22.2% and 26.4% for surgery, as well as for the transapical TAVR subgroup (29% vs. 28%, respectively).

A preliminary subgroup analysis suggests that there may be a possible benefit with TAVR in women and patients without prior coronary artery bypass surgery, but Dr. Smith said that those results should be interpreted cautiously.

Overall, the TAVR mortality of 3.4% at 30-days was the lowest reported in any series, despite the use of an early-generation device and limited previous operator experience, he said, noting that nine of the participating centers had never performed TAVR before the trial.

Symptom improvement, including NYHA class and 6-minute walk distance, favored TAVR at 30 days and was similar to conventional surgery at 1 year, he said.

Coinvestigator Dr. Murat Tuzcu, vice chair of the department of cardiovascular medicine at the Cleveland Clinic, stressed that the results were accomplished only through unprecedented teamwork among cardiologists, surgeons, and imaging experts, who consulted on each case in the trial.

"I want to emphasize that if we fail to pay equal attention to what we have done in this trial after the device is approved, I don’t think we will be able to replicate the same results," he said.

Several speakers at the press conference noted the balancing act that all clinicians will face regarding public demand for the new procedure.

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, observed that centers will face substantial up-front costs in the adoption of TAVR, including hybrid surgical/interventional suites, and that this will restrict initial uptake to high-volume centers of excellence.

The 3.4% mortality rate represents an "amazing effort," particularly in the use of the larger, first-generation device, said invited discussant Dr. Martyn Thomas, clinical director of cardiothoracic services at St. Thomas’ Hospital, London. The delivery catheters used in PARTNER are sized at 22 and 24 French, which corresponds to an outside diameter of 7-8 mm. The size of catheters is down to 16-Fr in Europe, where more than 5,000 TAVR procedures have been done and where both the Edwards Lifesciences Corp.’s Sapien valve that was used in PARTNER and the Medtronic Inc.’s CoreValve are already on the market.

Recruitment began in February for the PARTNER II trial that evaluated the smaller Edwards Sapien XT device and the later generation NovaFlex delivery system among inoperable patients with symptomatic severe aortic stenosis. The trial is expected to enroll 600 patients, and is targeted for primary completion in December 2011.

When asked whether the advent of newer, thinner devices will mean adoption in patients with lower risk, Dr. Smith replied that the adoption of TAVR will "march steadily down the risk categories."

Edwards Lifesciences sponsored the trial. Dr. Smith and his coauthors reported no conflicts of interest.