Patrice Wendling

DETROIT – Preinjury use of warfarin, but not aspirin or clopidogrel, significantly increased the risk of death in a retrospective analysis of 3,488 trauma patients.

Overall, mortality was 13.6% for patients on warfarin (Coumadin), aspirin, clopidogrel (Plavix), or various combinations, compared with 6.2% for patients not on these medications.

When mortality data were broken down by drug, warfarin demonstrated a mortality of 24% vs. 6% for controls.

After they adjusted for the potential confounders of age and injury severity score, the researchers found that the relative risk of a patient on warfarin dying during hospitalization as a result of their injury remained significant at 3.9, first-year resident Dr. Travis Arnold reported on behalf of his colleagues and lead author Dr. Carrie Jahraus at Albany (N.Y.) Medical College.

Surprisingly, aspirin and clopidogrel were not significantly associated with increased mortality at 12.3% and 9.3%, respectively, when adjusted for confounders.

"With aspirin and, [perhaps] clopidogrel, there may be some protective mechanism that we don’t fully understand," senior author Dr. Daniel Bonville said in an interview, adding that other groups have found similar results for the two agents.

All of the drugs increased the risk of intracranial hemorrhage when compared with controls (50% vs. 30%). The adjusted relative risk was 3.2 for warfarin, 1.9 for patients on warfarin plus clopidogrel, and 1.6 for those on aspirin or other combinations.

A total of 3,488 trauma patients were identified in the Albany Medical College database from September 2004 to December 2007. Of these, 456 patients were on some form of anticoagulation or antiplatelet therapy including 91 patients on warfarin alone, 228 on aspirin, 43 on clopidogrel, and 94 on various combinations. The mean warfarin international normalized ratio (INR) level was within the therapeutic window at 2.4, with 95% of patients falling between 2.2 and 2.6, Dr. Arnold said.

The percentage of patients in the treatment and control groups who experienced a blunt trauma was similar at 99% vs. 93%, respectively, as was the percentage with Injury Severity Scores greater than 15 (55% vs. 50%, respectively).

Hospital length of stay greater than 10 days was similar at 30% for the treatment group vs. 24% for controls, and remained similar after adjustment, Dr. Arnold said.

The percentage of patients discharged to home was significantly lower at 48% among patients on warfarin and antiplatelet agents vs. 74% for controls (P less than .01). This difference disappeared when adjusted for age.

When the researchers compared the subgroup of 191 patients who had intracranial hemorrhage with controls, only warfarin increased mortality (29% vs. 6%, adjusted RR 3.1) and the need for craniotomy (15% vs. 7%, adjusted RR 2.2), Dr. Arnold said.

He concluded that warfarin continues to be a necessary evil for many patients with coronary artery disease or history of stroke and advocated for greater patient education by primary care providers on the risks of anticoagulants.

Invited discussant Dr. Mark Hemmila, with the University of Michigan, Ann Arbor, said it is fortunate that only warfarin increases the risk of mortality given how difficult it is to reverse the effects of aspirin and clopidogrel, but that he would rank clopidogrel ahead of Coumadin and aspirin in terms of dangerousness. He asked Dr. Arnold to speculate on why no effect was observed and how the researchers recommend evaluating patients on warfarin.

Dr. Arnold said if a patient is on warfarin and has significant trauma and an elevated INR, warfarin reversal is initiated prior to obtaining computed tomography imaging. Factor VII is used, although they are transitioning more to the prothrombin complex. He said it is unclear why no impact on mortality was observed for aspirin given the large number of aspirin users in the study and that an effect would likely have been observed had there been more clopidogrel patients.

A recent analysis of 1.2 million patients in the American College of Surgeons’ National Trauma Data Bank reported that warfarin was associated with an increased risk of death, regardless of type of injury, indication for anticoagulation, or comorbidities. In all, 9.3% of warfarin-users died from their injuries vs. 4.8% of nonusers (Arch. Surg. 2011 [doi:10.1001/archsurg.2010.313]).

The researchers disclosed no conflicts of interest.

DETROIT – Preinjury use of warfarin, but not aspirin or clopidogrel, significantly increased the risk of death in a retrospective analysis of 3,488 trauma patients.

Overall, mortality was 13.6% for patients on warfarin (Coumadin), aspirin, clopidogrel (Plavix), or various combinations, compared with 6.2% for patients not on these medications.

When mortality data were broken down by drug, warfarin demonstrated a mortality of 24% vs. 6% for controls.

After they adjusted for the potential confounders of age and injury severity score, the researchers found that the relative risk of a patient on warfarin dying during hospitalization as a result of their injury remained significant at 3.9, first-year resident Dr. Travis Arnold reported on behalf of his colleagues and lead author Dr. Carrie Jahraus at Albany (N.Y.) Medical College.

Surprisingly, aspirin and clopidogrel were not significantly associated with increased mortality at 12.3% and 9.3%, respectively, when adjusted for confounders.

"With aspirin and, [perhaps] clopidogrel, there may be some protective mechanism that we don’t fully understand," senior author Dr. Daniel Bonville said in an interview, adding that other groups have found similar results for the two agents.

All of the drugs increased the risk of intracranial hemorrhage when compared with controls (50% vs. 30%). The adjusted relative risk was 3.2 for warfarin, 1.9 for patients on warfarin plus clopidogrel, and 1.6 for those on aspirin or other combinations.

A total of 3,488 trauma patients were identified in the Albany Medical College database from September 2004 to December 2007. Of these, 456 patients were on some form of anticoagulation or antiplatelet therapy including 91 patients on warfarin alone, 228 on aspirin, 43 on clopidogrel, and 94 on various combinations. The mean warfarin international normalized ratio (INR) level was within the therapeutic window at 2.4, with 95% of patients falling between 2.2 and 2.6, Dr. Arnold said.

The percentage of patients in the treatment and control groups who experienced a blunt trauma was similar at 99% vs. 93%, respectively, as was the percentage with Injury Severity Scores greater than 15 (55% vs. 50%, respectively).

Hospital length of stay greater than 10 days was similar at 30% for the treatment group vs. 24% for controls, and remained similar after adjustment, Dr. Arnold said.

The percentage of patients discharged to home was significantly lower at 48% among patients on warfarin and antiplatelet agents vs. 74% for controls (P less than .01). This difference disappeared when adjusted for age.

When the researchers compared the subgroup of 191 patients who had intracranial hemorrhage with controls, only warfarin increased mortality (29% vs. 6%, adjusted RR 3.1) and the need for craniotomy (15% vs. 7%, adjusted RR 2.2), Dr. Arnold said.

He concluded that warfarin continues to be a necessary evil for many patients with coronary artery disease or history of stroke and advocated for greater patient education by primary care providers on the risks of anticoagulants.

Invited discussant Dr. Mark Hemmila, with the University of Michigan, Ann Arbor, said it is fortunate that only warfarin increases the risk of mortality given how difficult it is to reverse the effects of aspirin and clopidogrel, but that he would rank clopidogrel ahead of Coumadin and aspirin in terms of dangerousness. He asked Dr. Arnold to speculate on why no effect was observed and how the researchers recommend evaluating patients on warfarin.

Dr. Arnold said if a patient is on warfarin and has significant trauma and an elevated INR, warfarin reversal is initiated prior to obtaining computed tomography imaging. Factor VII is used, although they are transitioning more to the prothrombin complex. He said it is unclear why no impact on mortality was observed for aspirin given the large number of aspirin users in the study and that an effect would likely have been observed had there been more clopidogrel patients.

A recent analysis of 1.2 million patients in the American College of Surgeons’ National Trauma Data Bank reported that warfarin was associated with an increased risk of death, regardless of type of injury, indication for anticoagulation, or comorbidities. In all, 9.3% of warfarin-users died from their injuries vs. 4.8% of nonusers (Arch. Surg. 2011 [doi:10.1001/archsurg.2010.313]).

The researchers disclosed no conflicts of interest.

DETROIT – Preinjury use of warfarin, but not aspirin or clopidogrel, significantly increased the risk of death in a retrospective analysis of 3,488 trauma patients.

Overall, mortality was 13.6% for patients on warfarin (Coumadin), aspirin, clopidogrel (Plavix), or various combinations, compared with 6.2% for patients not on these medications.

When mortality data were broken down by drug, warfarin demonstrated a mortality of 24% vs. 6% for controls.

After they adjusted for the potential confounders of age and injury severity score, the researchers found that the relative risk of a patient on warfarin dying during hospitalization as a result of their injury remained significant at 3.9, first-year resident Dr. Travis Arnold reported on behalf of his colleagues and lead author Dr. Carrie Jahraus at Albany (N.Y.) Medical College.

Surprisingly, aspirin and clopidogrel were not significantly associated with increased mortality at 12.3% and 9.3%, respectively, when adjusted for confounders.

"With aspirin and, [perhaps] clopidogrel, there may be some protective mechanism that we don’t fully understand," senior author Dr. Daniel Bonville said in an interview, adding that other groups have found similar results for the two agents.

All of the drugs increased the risk of intracranial hemorrhage when compared with controls (50% vs. 30%). The adjusted relative risk was 3.2 for warfarin, 1.9 for patients on warfarin plus clopidogrel, and 1.6 for those on aspirin or other combinations.

A total of 3,488 trauma patients were identified in the Albany Medical College database from September 2004 to December 2007. Of these, 456 patients were on some form of anticoagulation or antiplatelet therapy including 91 patients on warfarin alone, 228 on aspirin, 43 on clopidogrel, and 94 on various combinations. The mean warfarin international normalized ratio (INR) level was within the therapeutic window at 2.4, with 95% of patients falling between 2.2 and 2.6, Dr. Arnold said.

The percentage of patients in the treatment and control groups who experienced a blunt trauma was similar at 99% vs. 93%, respectively, as was the percentage with Injury Severity Scores greater than 15 (55% vs. 50%, respectively).

Hospital length of stay greater than 10 days was similar at 30% for the treatment group vs. 24% for controls, and remained similar after adjustment, Dr. Arnold said.

The percentage of patients discharged to home was significantly lower at 48% among patients on warfarin and antiplatelet agents vs. 74% for controls (P less than .01). This difference disappeared when adjusted for age.

When the researchers compared the subgroup of 191 patients who had intracranial hemorrhage with controls, only warfarin increased mortality (29% vs. 6%, adjusted RR 3.1) and the need for craniotomy (15% vs. 7%, adjusted RR 2.2), Dr. Arnold said.

He concluded that warfarin continues to be a necessary evil for many patients with coronary artery disease or history of stroke and advocated for greater patient education by primary care providers on the risks of anticoagulants.

Invited discussant Dr. Mark Hemmila, with the University of Michigan, Ann Arbor, said it is fortunate that only warfarin increases the risk of mortality given how difficult it is to reverse the effects of aspirin and clopidogrel, but that he would rank clopidogrel ahead of Coumadin and aspirin in terms of dangerousness. He asked Dr. Arnold to speculate on why no effect was observed and how the researchers recommend evaluating patients on warfarin.

Dr. Arnold said if a patient is on warfarin and has significant trauma and an elevated INR, warfarin reversal is initiated prior to obtaining computed tomography imaging. Factor VII is used, although they are transitioning more to the prothrombin complex. He said it is unclear why no impact on mortality was observed for aspirin given the large number of aspirin users in the study and that an effect would likely have been observed had there been more clopidogrel patients.

A recent analysis of 1.2 million patients in the American College of Surgeons’ National Trauma Data Bank reported that warfarin was associated with an increased risk of death, regardless of type of injury, indication for anticoagulation, or comorbidities. In all, 9.3% of warfarin-users died from their injuries vs. 4.8% of nonusers (Arch. Surg. 2011 [doi:10.1001/archsurg.2010.313]).

The researchers disclosed no conflicts of interest.

DETROIT – Preinjury use of warfarin, but not aspirin or clopidogrel, significantly increased the risk of death in a retrospective analysis of 3,488 trauma patients.

Overall, mortality was 13.6% for patients on warfarin (Coumadin), aspirin, clopidogrel (Plavix), or various combinations, compared with 6.2% for patients not on these medications.

When mortality data were broken down by drug, warfarin demonstrated a mortality of 24% vs. 6% for controls.

After they adjusted for the potential confounders of age and injury severity score, the researchers found that the relative risk of a patient on warfarin dying during hospitalization as a result of their injury remained significant at 3.9, first-year resident Dr. Travis Arnold reported on behalf of his colleagues and lead author Dr. Carrie Jahraus at Albany (N.Y.) Medical College.

Surprisingly, aspirin and clopidogrel were not significantly associated with increased mortality at 12.3% and 9.3%, respectively, when adjusted for confounders.

"With aspirin and, [perhaps] clopidogrel, there may be some protective mechanism that we don’t fully understand," senior author Dr. Daniel Bonville said in an interview, adding that other groups have found similar results for the two agents.

All of the drugs increased the risk of intracranial hemorrhage when compared with controls (50% vs. 30%). The adjusted relative risk was 3.2 for warfarin, 1.9 for patients on warfarin plus clopidogrel, and 1.6 for those on aspirin or other combinations.

A total of 3,488 trauma patients were identified in the Albany Medical College database from September 2004 to December 2007. Of these, 456 patients were on some form of anticoagulation or antiplatelet therapy including 91 patients on warfarin alone, 228 on aspirin, 43 on clopidogrel, and 94 on various combinations. The mean warfarin international normalized ratio (INR) level was within the therapeutic window at 2.4, with 95% of patients falling between 2.2 and 2.6, Dr. Arnold said.

The percentage of patients in the treatment and control groups who experienced a blunt trauma was similar at 99% vs. 93%, respectively, as was the percentage with Injury Severity Scores greater than 15 (55% vs. 50%, respectively).

Hospital length of stay greater than 10 days was similar at 30% for the treatment group vs. 24% for controls, and remained similar after adjustment, Dr. Arnold said.

The percentage of patients discharged to home was significantly lower at 48% among patients on warfarin and antiplatelet agents vs. 74% for controls (P less than .01). This difference disappeared when adjusted for age.

When the researchers compared the subgroup of 191 patients who had intracranial hemorrhage with controls, only warfarin increased mortality (29% vs. 6%, adjusted RR 3.1) and the need for craniotomy (15% vs. 7%, adjusted RR 2.2), Dr. Arnold said.

He concluded that warfarin continues to be a necessary evil for many patients with coronary artery disease or history of stroke and advocated for greater patient education by primary care providers on the risks of anticoagulants.

Invited discussant Dr. Mark Hemmila, with the University of Michigan, Ann Arbor, said it is fortunate that only warfarin increases the risk of mortality given how difficult it is to reverse the effects of aspirin and clopidogrel, but that he would rank clopidogrel ahead of Coumadin and aspirin in terms of dangerousness. He asked Dr. Arnold to speculate on why no effect was observed and how the researchers recommend evaluating patients on warfarin.

Dr. Arnold said if a patient is on warfarin and has significant trauma and an elevated INR, warfarin reversal is initiated prior to obtaining computed tomography imaging. Factor VII is used, although they are transitioning more to the prothrombin complex. He said it is unclear why no impact on mortality was observed for aspirin given the large number of aspirin users in the study and that an effect would likely have been observed had there been more clopidogrel patients.

A recent analysis of 1.2 million patients in the American College of Surgeons’ National Trauma Data Bank reported that warfarin was associated with an increased risk of death, regardless of type of injury, indication for anticoagulation, or comorbidities. In all, 9.3% of warfarin-users died from their injuries vs. 4.8% of nonusers (Arch. Surg. 2011 [doi:10.1001/archsurg.2010.313]).

The researchers disclosed no conflicts of interest.

DETROIT – Preinjury use of warfarin, but not aspirin or clopidogrel, significantly increased the risk of death in a retrospective analysis of 3,488 trauma patients.

Overall, mortality was 13.6% for patients on warfarin (Coumadin), aspirin, clopidogrel (Plavix), or various combinations, compared with 6.2% for patients not on these medications.

When mortality data were broken down by drug, warfarin demonstrated a mortality of 24% vs. 6% for controls.

After they adjusted for the potential confounders of age and injury severity score, the researchers found that the relative risk of a patient on warfarin dying during hospitalization as a result of their injury remained significant at 3.9, first-year resident Dr. Travis Arnold reported on behalf of his colleagues and lead author Dr. Carrie Jahraus at Albany (N.Y.) Medical College.

Surprisingly, aspirin and clopidogrel were not significantly associated with increased mortality at 12.3% and 9.3%, respectively, when adjusted for confounders.

"With aspirin and, [perhaps] clopidogrel, there may be some protective mechanism that we don’t fully understand," senior author Dr. Daniel Bonville said in an interview, adding that other groups have found similar results for the two agents.

All of the drugs increased the risk of intracranial hemorrhage when compared with controls (50% vs. 30%). The adjusted relative risk was 3.2 for warfarin, 1.9 for patients on warfarin plus clopidogrel, and 1.6 for those on aspirin or other combinations.

A total of 3,488 trauma patients were identified in the Albany Medical College database from September 2004 to December 2007. Of these, 456 patients were on some form of anticoagulation or antiplatelet therapy including 91 patients on warfarin alone, 228 on aspirin, 43 on clopidogrel, and 94 on various combinations. The mean warfarin international normalized ratio (INR) level was within the therapeutic window at 2.4, with 95% of patients falling between 2.2 and 2.6, Dr. Arnold said.

The percentage of patients in the treatment and control groups who experienced a blunt trauma was similar at 99% vs. 93%, respectively, as was the percentage with Injury Severity Scores greater than 15 (55% vs. 50%, respectively).

Hospital length of stay greater than 10 days was similar at 30% for the treatment group vs. 24% for controls, and remained similar after adjustment, Dr. Arnold said.

The percentage of patients discharged to home was significantly lower at 48% among patients on warfarin and antiplatelet agents vs. 74% for controls (P less than .01). This difference disappeared when adjusted for age.

When the researchers compared the subgroup of 191 patients who had intracranial hemorrhage with controls, only warfarin increased mortality (29% vs. 6%, adjusted RR 3.1) and the need for craniotomy (15% vs. 7%, adjusted RR 2.2), Dr. Arnold said.

He concluded that warfarin continues to be a necessary evil for many patients with coronary artery disease or history of stroke and advocated for greater patient education by primary care providers on the risks of anticoagulants.

Invited discussant Dr. Mark Hemmila, with the University of Michigan, Ann Arbor, said it is fortunate that only warfarin increases the risk of mortality given how difficult it is to reverse the effects of aspirin and clopidogrel, but that he would rank clopidogrel ahead of Coumadin and aspirin in terms of dangerousness. He asked Dr. Arnold to speculate on why no effect was observed and how the researchers recommend evaluating patients on warfarin.

Dr. Arnold said if a patient is on warfarin and has significant trauma and an elevated INR, warfarin reversal is initiated prior to obtaining computed tomography imaging. Factor VII is used, although they are transitioning more to the prothrombin complex. He said it is unclear why no impact on mortality was observed for aspirin given the large number of aspirin users in the study and that an effect would likely have been observed had there been more clopidogrel patients.

A recent analysis of 1.2 million patients in the American College of Surgeons’ National Trauma Data Bank reported that warfarin was associated with an increased risk of death, regardless of type of injury, indication for anticoagulation, or comorbidities. In all, 9.3% of warfarin-users died from their injuries vs. 4.8% of nonusers (Arch. Surg. 2011 [doi:10.1001/archsurg.2010.313]).

The researchers disclosed no conflicts of interest.

DETROIT – Preinjury use of warfarin, but not aspirin or clopidogrel, significantly increased the risk of death in a retrospective analysis of 3,488 trauma patients.

Overall, mortality was 13.6% for patients on warfarin (Coumadin), aspirin, clopidogrel (Plavix), or various combinations, compared with 6.2% for patients not on these medications.

When mortality data were broken down by drug, warfarin demonstrated a mortality of 24% vs. 6% for controls.

After they adjusted for the potential confounders of age and injury severity score, the researchers found that the relative risk of a patient on warfarin dying during hospitalization as a result of their injury remained significant at 3.9, first-year resident Dr. Travis Arnold reported on behalf of his colleagues and lead author Dr. Carrie Jahraus at Albany (N.Y.) Medical College.

Surprisingly, aspirin and clopidogrel were not significantly associated with increased mortality at 12.3% and 9.3%, respectively, when adjusted for confounders.

"With aspirin and, [perhaps] clopidogrel, there may be some protective mechanism that we don’t fully understand," senior author Dr. Daniel Bonville said in an interview, adding that other groups have found similar results for the two agents.

All of the drugs increased the risk of intracranial hemorrhage when compared with controls (50% vs. 30%). The adjusted relative risk was 3.2 for warfarin, 1.9 for patients on warfarin plus clopidogrel, and 1.6 for those on aspirin or other combinations.

A total of 3,488 trauma patients were identified in the Albany Medical College database from September 2004 to December 2007. Of these, 456 patients were on some form of anticoagulation or antiplatelet therapy including 91 patients on warfarin alone, 228 on aspirin, 43 on clopidogrel, and 94 on various combinations. The mean warfarin international normalized ratio (INR) level was within the therapeutic window at 2.4, with 95% of patients falling between 2.2 and 2.6, Dr. Arnold said.

The percentage of patients in the treatment and control groups who experienced a blunt trauma was similar at 99% vs. 93%, respectively, as was the percentage with Injury Severity Scores greater than 15 (55% vs. 50%, respectively).

Hospital length of stay greater than 10 days was similar at 30% for the treatment group vs. 24% for controls, and remained similar after adjustment, Dr. Arnold said.

The percentage of patients discharged to home was significantly lower at 48% among patients on warfarin and antiplatelet agents vs. 74% for controls (P less than .01). This difference disappeared when adjusted for age.

When the researchers compared the subgroup of 191 patients who had intracranial hemorrhage with controls, only warfarin increased mortality (29% vs. 6%, adjusted RR 3.1) and the need for craniotomy (15% vs. 7%, adjusted RR 2.2), Dr. Arnold said.

He concluded that warfarin continues to be a necessary evil for many patients with coronary artery disease or history of stroke and advocated for greater patient education by primary care providers on the risks of anticoagulants.

Invited discussant Dr. Mark Hemmila, with the University of Michigan, Ann Arbor, said it is fortunate that only warfarin increases the risk of mortality given how difficult it is to reverse the effects of aspirin and clopidogrel, but that he would rank clopidogrel ahead of Coumadin and aspirin in terms of dangerousness. He asked Dr. Arnold to speculate on why no effect was observed and how the researchers recommend evaluating patients on warfarin.

Dr. Arnold said if a patient is on warfarin and has significant trauma and an elevated INR, warfarin reversal is initiated prior to obtaining computed tomography imaging. Factor VII is used, although they are transitioning more to the prothrombin complex. He said it is unclear why no impact on mortality was observed for aspirin given the large number of aspirin users in the study and that an effect would likely have been observed had there been more clopidogrel patients.

A recent analysis of 1.2 million patients in the American College of Surgeons’ National Trauma Data Bank reported that warfarin was associated with an increased risk of death, regardless of type of injury, indication for anticoagulation, or comorbidities. In all, 9.3% of warfarin-users died from their injuries vs. 4.8% of nonusers (Arch. Surg. 2011 [doi:10.1001/archsurg.2010.313]).

The researchers disclosed no conflicts of interest.

SAN ANTONIO – Young, healthy patients with early-stage colon cancer are more likely to be overtreated, whereas older, uninsured patients with higher-risk disease tend to be undertreated, according to an analysis of 236,964 cases.

"Although adherence [to stage-specific treatment guidelines] has increased over the past 5 years, significant variability still exists," Dr. Ryaz B. Chagpar said during a plenary session at a symposium sponsored by the Society of Surgical Oncology.

Treatment guideline adherence has been proposed as a potential measure of the quality of cancer care. Colon cancer guideline adherence is a potentially attractive quality measure since consensus on treatment standards exists among several agencies including the National Comprehensive Cancer Network (NCCN), the American Society for Clinical Oncology, and the National Quality Forum, he said. However, nationwide assessment of current stage-specific colon cancer treatment practices is lacking.

Using the National Cancer Data Base, Dr. Chagpar and his colleagues in the department of surgical oncology at MD Anderson Cancer Center in Houston, identified all patients diagnosed with colon cancer from 2003 to 2007. The database captures about 70% of all annual cancer diagnoses within the United States from more than 1,430 hospitals, and is a joint program of the American College of Surgeons Commission on Cancer and the American Cancer Society.

After excluding hospitals that were only diagnostic, the researchers identified 236,964 patients. The patients were then restaged from pathological variables according to the American Joint Committee on Cancer 6th edition staging manual, and grouped according to whether their treatment was adherent with NCCN guidelines. Of note, stage II disease was stratified into low- and high-risk disease based on the guidelines, with the latter defined as patients with T4 lesions, those with less than a 12-node lymphadenectomy, and tumors categorized as at least grade 3 or resected with positive margins.

Adherence for stage I and low-risk stage II colon cancer was defined as surgical resection. Nonadherence included the recommendation of adjuvant chemotherapy, independent of whether the treatment was actually received (overtreatment), or no adequate surgical resection (undertreatment), Dr. Chagpar said.

For stage II high-risk disease, adherence was defined as the consideration of adjuvant chemotherapy following surgical resection. Overtreatment included the addition of radiation to chemotherapy and undertreatment was surgical resection alone.

Adherence for stage III disease was defined as that for stage II high-risk disease. The only difference for stage IV adherence was the recommendation of chemotherapy, independent of whether surgical resection was performed, he explained.

Patients with stage I colon cancer were significantly more likely to receive guideline-based treatment, at 95.5%, compared with 74% for low-risk stage II, just 27% for high-risk stage II, 64.5% for stage III, and 68% for stage IV (P value less than .0005).

The researchers then performed hierarchical regression modeling that controlled for heterogeneity at both the hospital level and patient level to determine factors associated with adherence.

Interestingly, for stage I and low-risk stage II disease, increasing age as well as increasing Charlson-Deyo Comorbidity Index was associated with a greater likelihood of receiving adherent treatment, whereas for higher-risk disease, older patients as well as those with a greater number of comorbidities were less likely to receive guideline-based treatment, Dr. Chagpar said.

Also, a later year of diagnosis (2007 vs. 2003) was associated with greater likelihood of receiving guideline-based treatment regardless of disease stage. The same was true for having private insurance, with the exception of low-risk stage II disease.

Nonadherence for stage I and low-risk patients was largely attributable to overtreatment in the form of recommendations for adjuvant chemotherapy, particularly in young, healthy patients and those with private insurance, Dr. Chagpar said.

Nonadherence for high-risk stage II, stage III, and stage IV disease was primarily due to undertreatment, particularly for older, uninsured patients and those with a number of preexisting comorbidities.

"Given that guideline-based care, however, does not necessarily translate into improved survival and patient-reported outcomes, the impact of nonadherence on the quality of cancer care needs to be further elucidated," he concluded.

Limitations of the study include variability in the level of evidence used to construct NCCN guidelines; a lack of pathological staging data for 15% of patients; and a lack of data on some factors used to characterize high-risk stage II disease, such as lymphatic vascular invasion and obstruction. In addition, systemic therapy is often underreported in cancer registries, the authors said.

The authors reported no conflicts of interest.

SAN ANTONIO – Young, healthy patients with early-stage colon cancer are more likely to be overtreated, whereas older, uninsured patients with higher-risk disease tend to be undertreated, according to an analysis of 236,964 cases.

"Although adherence [to stage-specific treatment guidelines] has increased over the past 5 years, significant variability still exists," Dr. Ryaz B. Chagpar said during a plenary session at a symposium sponsored by the Society of Surgical Oncology.

Treatment guideline adherence has been proposed as a potential measure of the quality of cancer care. Colon cancer guideline adherence is a potentially attractive quality measure since consensus on treatment standards exists among several agencies including the National Comprehensive Cancer Network (NCCN), the American Society for Clinical Oncology, and the National Quality Forum, he said. However, nationwide assessment of current stage-specific colon cancer treatment practices is lacking.

Using the National Cancer Data Base, Dr. Chagpar and his colleagues in the department of surgical oncology at MD Anderson Cancer Center in Houston, identified all patients diagnosed with colon cancer from 2003 to 2007. The database captures about 70% of all annual cancer diagnoses within the United States from more than 1,430 hospitals, and is a joint program of the American College of Surgeons Commission on Cancer and the American Cancer Society.

After excluding hospitals that were only diagnostic, the researchers identified 236,964 patients. The patients were then restaged from pathological variables according to the American Joint Committee on Cancer 6th edition staging manual, and grouped according to whether their treatment was adherent with NCCN guidelines. Of note, stage II disease was stratified into low- and high-risk disease based on the guidelines, with the latter defined as patients with T4 lesions, those with less than a 12-node lymphadenectomy, and tumors categorized as at least grade 3 or resected with positive margins.

Adherence for stage I and low-risk stage II colon cancer was defined as surgical resection. Nonadherence included the recommendation of adjuvant chemotherapy, independent of whether the treatment was actually received (overtreatment), or no adequate surgical resection (undertreatment), Dr. Chagpar said.

For stage II high-risk disease, adherence was defined as the consideration of adjuvant chemotherapy following surgical resection. Overtreatment included the addition of radiation to chemotherapy and undertreatment was surgical resection alone.

Adherence for stage III disease was defined as that for stage II high-risk disease. The only difference for stage IV adherence was the recommendation of chemotherapy, independent of whether surgical resection was performed, he explained.

Patients with stage I colon cancer were significantly more likely to receive guideline-based treatment, at 95.5%, compared with 74% for low-risk stage II, just 27% for high-risk stage II, 64.5% for stage III, and 68% for stage IV (P value less than .0005).

The researchers then performed hierarchical regression modeling that controlled for heterogeneity at both the hospital level and patient level to determine factors associated with adherence.

Interestingly, for stage I and low-risk stage II disease, increasing age as well as increasing Charlson-Deyo Comorbidity Index was associated with a greater likelihood of receiving adherent treatment, whereas for higher-risk disease, older patients as well as those with a greater number of comorbidities were less likely to receive guideline-based treatment, Dr. Chagpar said.

Also, a later year of diagnosis (2007 vs. 2003) was associated with greater likelihood of receiving guideline-based treatment regardless of disease stage. The same was true for having private insurance, with the exception of low-risk stage II disease.

Nonadherence for stage I and low-risk patients was largely attributable to overtreatment in the form of recommendations for adjuvant chemotherapy, particularly in young, healthy patients and those with private insurance, Dr. Chagpar said.

Nonadherence for high-risk stage II, stage III, and stage IV disease was primarily due to undertreatment, particularly for older, uninsured patients and those with a number of preexisting comorbidities.

"Given that guideline-based care, however, does not necessarily translate into improved survival and patient-reported outcomes, the impact of nonadherence on the quality of cancer care needs to be further elucidated," he concluded.

Limitations of the study include variability in the level of evidence used to construct NCCN guidelines; a lack of pathological staging data for 15% of patients; and a lack of data on some factors used to characterize high-risk stage II disease, such as lymphatic vascular invasion and obstruction. In addition, systemic therapy is often underreported in cancer registries, the authors said.

The authors reported no conflicts of interest.

SAN ANTONIO – Young, healthy patients with early-stage colon cancer are more likely to be overtreated, whereas older, uninsured patients with higher-risk disease tend to be undertreated, according to an analysis of 236,964 cases.

"Although adherence [to stage-specific treatment guidelines] has increased over the past 5 years, significant variability still exists," Dr. Ryaz B. Chagpar said during a plenary session at a symposium sponsored by the Society of Surgical Oncology.

Treatment guideline adherence has been proposed as a potential measure of the quality of cancer care. Colon cancer guideline adherence is a potentially attractive quality measure since consensus on treatment standards exists among several agencies including the National Comprehensive Cancer Network (NCCN), the American Society for Clinical Oncology, and the National Quality Forum, he said. However, nationwide assessment of current stage-specific colon cancer treatment practices is lacking.

Using the National Cancer Data Base, Dr. Chagpar and his colleagues in the department of surgical oncology at MD Anderson Cancer Center in Houston, identified all patients diagnosed with colon cancer from 2003 to 2007. The database captures about 70% of all annual cancer diagnoses within the United States from more than 1,430 hospitals, and is a joint program of the American College of Surgeons Commission on Cancer and the American Cancer Society.

After excluding hospitals that were only diagnostic, the researchers identified 236,964 patients. The patients were then restaged from pathological variables according to the American Joint Committee on Cancer 6th edition staging manual, and grouped according to whether their treatment was adherent with NCCN guidelines. Of note, stage II disease was stratified into low- and high-risk disease based on the guidelines, with the latter defined as patients with T4 lesions, those with less than a 12-node lymphadenectomy, and tumors categorized as at least grade 3 or resected with positive margins.

Adherence for stage I and low-risk stage II colon cancer was defined as surgical resection. Nonadherence included the recommendation of adjuvant chemotherapy, independent of whether the treatment was actually received (overtreatment), or no adequate surgical resection (undertreatment), Dr. Chagpar said.

For stage II high-risk disease, adherence was defined as the consideration of adjuvant chemotherapy following surgical resection. Overtreatment included the addition of radiation to chemotherapy and undertreatment was surgical resection alone.

Adherence for stage III disease was defined as that for stage II high-risk disease. The only difference for stage IV adherence was the recommendation of chemotherapy, independent of whether surgical resection was performed, he explained.

Patients with stage I colon cancer were significantly more likely to receive guideline-based treatment, at 95.5%, compared with 74% for low-risk stage II, just 27% for high-risk stage II, 64.5% for stage III, and 68% for stage IV (P value less than .0005).

The researchers then performed hierarchical regression modeling that controlled for heterogeneity at both the hospital level and patient level to determine factors associated with adherence.

Interestingly, for stage I and low-risk stage II disease, increasing age as well as increasing Charlson-Deyo Comorbidity Index was associated with a greater likelihood of receiving adherent treatment, whereas for higher-risk disease, older patients as well as those with a greater number of comorbidities were less likely to receive guideline-based treatment, Dr. Chagpar said.

Also, a later year of diagnosis (2007 vs. 2003) was associated with greater likelihood of receiving guideline-based treatment regardless of disease stage. The same was true for having private insurance, with the exception of low-risk stage II disease.

Nonadherence for stage I and low-risk patients was largely attributable to overtreatment in the form of recommendations for adjuvant chemotherapy, particularly in young, healthy patients and those with private insurance, Dr. Chagpar said.

Nonadherence for high-risk stage II, stage III, and stage IV disease was primarily due to undertreatment, particularly for older, uninsured patients and those with a number of preexisting comorbidities.

"Given that guideline-based care, however, does not necessarily translate into improved survival and patient-reported outcomes, the impact of nonadherence on the quality of cancer care needs to be further elucidated," he concluded.

Limitations of the study include variability in the level of evidence used to construct NCCN guidelines; a lack of pathological staging data for 15% of patients; and a lack of data on some factors used to characterize high-risk stage II disease, such as lymphatic vascular invasion and obstruction. In addition, systemic therapy is often underreported in cancer registries, the authors said.

The authors reported no conflicts of interest.

NEW ORLEANS – The cost of transcatheter aortic valve replacement among patients with inoperable severe aortic stenosis is in line with other accepted cardiovascular procedures, according to an economic analysis of the PARTNER trial.

Index hospitalization costs for transcatheter aortic valve replacement (TAVR) were $78,540 based on an estimated cost of $30,000 for the investigational Edwards SAPIEN valve. TAVR was, however, associated with a projected gain in survival, resulting in overall lifetime cost effectiveness.

"In this extremely high-risk population, an elderly population, the intervention is adding roughly 2 years of life, and that is the return on investment," principal investigator Dr. Matthew Reynolds said during a press briefing at the annual meeting of the American College of Cardiology. "The cost-effectiveness ratio, when you do the math, works out to just over $50,000 per life-year gained."

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, said up-front hospital costs for TAVR will be high because of the need for a hybrid operative/interventional suite, but that as long as the risks and costs are reasonable, patients will opt for the percutaneous approach simply because they don’t want surgery.

During the formal study presentation, invited discussant Dr. Martyn Thomas, director of cardiovascular services at Guy’s and St. Thomas’ Hospitals, London, said clinicians in the United Kingdom were awaiting results of the cost analysis with bated breath to determine if TAVR could get the nod from the National Institute for Health and Clinical Excellence.

"When I plug in our numbers ... I get somewhere around £20,000 [U.S.$32,700] per QALY [quality-adjusted life-year], which for us would be absolutely perfect," Dr. Thomas said.

Anticipation regarding TAVR has been building since efficacy data reported last fall for the same 358 inoperable patients, known as cohort B, demonstrated a 20% survival benefit with TAVR at 1 year, compared with standard medical therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-6070).

The question, however, is whether the novel procedure will be cost effective in an increasingly heated climate of health care cost containment.

In an attempt to tackle the issue, Dr. Reynolds and his colleagues assessed lifetime incremental cost-effectiveness ratios (ICERs) and lifetime incremental costs per QALY using hospital billing data or MEDPAR when bills were unavailable. Costs from the last 6 months for surviving patients were used to project future costs beyond 12 months, while parametric survival models fit to the trial data were used to extrapolate patient-level life expectancy beyond the follow-up period.

The initial $78,540 price tag for TAVR includes $42,806 for procedural costs, $30,756 for nonprocedural expenses, and $4,978 for physician fees, said Dr. Reynolds, director of the Economics and Quality of Life Research Center at the Harvard Clinical Research Institute, Boston. Patients spent an average of 10 days in the hospital, including 4 days in the intensive care unit.

Twelve-month follow-up costs were $23,372 higher for patients treated with standard medical therapy. This was a result of significantly more hospitalizations in the control group than in the TAVR group (2.15 vs. 1.02), mainly due to cardiovascular causes (1.7 vs. 0.50), he said.

The estimated life expectancy was 3.1 years for patients treated with TAVR and 1.2 years for those treated with medical therapy, or a difference of 1.9 years.

The lifetime incremental cost per patient was $79,837, and the lifetime incremental gain in life expectancy was 1.59 years. This translated into an ICER of $50,212 per life-year gained and $61,889 per QALY, he said.

Additional analysis showed that if the price of the device were to drop to $20,000, the ICER would be $43,642 per life-year gained. In Europe, both the SAPIEN valve (Edwards Lifesciences) and the CoreValve (Medtronic) are already on the market.

On the basis of the data, TAVR in this older inoperable cohort falls very close to published cost-effectiveness estimates for implantable defibrillators and atrial fibrillation ablation, and is actually lower than current estimates for hemodialysis or percutaneous coronary intervention for stable coronary artery disease, Dr. Reynolds said.

"For patients with severe aortic stenosis who are unsuitable for surgical aortic valve replacement, TAVR significantly increases life expectancy at an incremental cost per life-year gained well within accepted values for commonly used cardiovascular technologies," he said.

When asked what the budget impact would be of adoption of TAVR, Dr. Reynolds said they have not performed such an analysis, but that an estimated 30% of patients with severe aortic stenosis do not undergo conventional open surgery.

Efficacy data presented at the same session by Dr. Craig Smith on cohort A of the PARTNER trial, revealed that all-cause mortality in 699 high-risk patients with severe aortic stenosis was the same at 1 year, at 24% with TAVR vs. 27% with conventional open surgery, but that the incidence of stroke was increased at 8.3% vs. 4.3%. Cost comparisons of TAVR vs. conventional surgery are not yet available.

Edwards Lifesciences provided grant support for the analysis.

NEW ORLEANS – The cost of transcatheter aortic valve replacement among patients with inoperable severe aortic stenosis is in line with other accepted cardiovascular procedures, according to an economic analysis of the PARTNER trial.

Index hospitalization costs for transcatheter aortic valve replacement (TAVR) were $78,540 based on an estimated cost of $30,000 for the investigational Edwards SAPIEN valve. TAVR was, however, associated with a projected gain in survival, resulting in overall lifetime cost effectiveness.

"In this extremely high-risk population, an elderly population, the intervention is adding roughly 2 years of life, and that is the return on investment," principal investigator Dr. Matthew Reynolds said during a press briefing at the annual meeting of the American College of Cardiology. "The cost-effectiveness ratio, when you do the math, works out to just over $50,000 per life-year gained."

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, said up-front hospital costs for TAVR will be high because of the need for a hybrid operative/interventional suite, but that as long as the risks and costs are reasonable, patients will opt for the percutaneous approach simply because they don’t want surgery.

During the formal study presentation, invited discussant Dr. Martyn Thomas, director of cardiovascular services at Guy’s and St. Thomas’ Hospitals, London, said clinicians in the United Kingdom were awaiting results of the cost analysis with bated breath to determine if TAVR could get the nod from the National Institute for Health and Clinical Excellence.

"When I plug in our numbers ... I get somewhere around £20,000 [U.S.$32,700] per QALY [quality-adjusted life-year], which for us would be absolutely perfect," Dr. Thomas said.

Anticipation regarding TAVR has been building since efficacy data reported last fall for the same 358 inoperable patients, known as cohort B, demonstrated a 20% survival benefit with TAVR at 1 year, compared with standard medical therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-6070).

The question, however, is whether the novel procedure will be cost effective in an increasingly heated climate of health care cost containment.

In an attempt to tackle the issue, Dr. Reynolds and his colleagues assessed lifetime incremental cost-effectiveness ratios (ICERs) and lifetime incremental costs per QALY using hospital billing data or MEDPAR when bills were unavailable. Costs from the last 6 months for surviving patients were used to project future costs beyond 12 months, while parametric survival models fit to the trial data were used to extrapolate patient-level life expectancy beyond the follow-up period.

The initial $78,540 price tag for TAVR includes $42,806 for procedural costs, $30,756 for nonprocedural expenses, and $4,978 for physician fees, said Dr. Reynolds, director of the Economics and Quality of Life Research Center at the Harvard Clinical Research Institute, Boston. Patients spent an average of 10 days in the hospital, including 4 days in the intensive care unit.

Twelve-month follow-up costs were $23,372 higher for patients treated with standard medical therapy. This was a result of significantly more hospitalizations in the control group than in the TAVR group (2.15 vs. 1.02), mainly due to cardiovascular causes (1.7 vs. 0.50), he said.

The estimated life expectancy was 3.1 years for patients treated with TAVR and 1.2 years for those treated with medical therapy, or a difference of 1.9 years.

The lifetime incremental cost per patient was $79,837, and the lifetime incremental gain in life expectancy was 1.59 years. This translated into an ICER of $50,212 per life-year gained and $61,889 per QALY, he said.

Additional analysis showed that if the price of the device were to drop to $20,000, the ICER would be $43,642 per life-year gained. In Europe, both the SAPIEN valve (Edwards Lifesciences) and the CoreValve (Medtronic) are already on the market.

On the basis of the data, TAVR in this older inoperable cohort falls very close to published cost-effectiveness estimates for implantable defibrillators and atrial fibrillation ablation, and is actually lower than current estimates for hemodialysis or percutaneous coronary intervention for stable coronary artery disease, Dr. Reynolds said.

"For patients with severe aortic stenosis who are unsuitable for surgical aortic valve replacement, TAVR significantly increases life expectancy at an incremental cost per life-year gained well within accepted values for commonly used cardiovascular technologies," he said.

When asked what the budget impact would be of adoption of TAVR, Dr. Reynolds said they have not performed such an analysis, but that an estimated 30% of patients with severe aortic stenosis do not undergo conventional open surgery.

Efficacy data presented at the same session by Dr. Craig Smith on cohort A of the PARTNER trial, revealed that all-cause mortality in 699 high-risk patients with severe aortic stenosis was the same at 1 year, at 24% with TAVR vs. 27% with conventional open surgery, but that the incidence of stroke was increased at 8.3% vs. 4.3%. Cost comparisons of TAVR vs. conventional surgery are not yet available.

Edwards Lifesciences provided grant support for the analysis.

NEW ORLEANS – The cost of transcatheter aortic valve replacement among patients with inoperable severe aortic stenosis is in line with other accepted cardiovascular procedures, according to an economic analysis of the PARTNER trial.

Index hospitalization costs for transcatheter aortic valve replacement (TAVR) were $78,540 based on an estimated cost of $30,000 for the investigational Edwards SAPIEN valve. TAVR was, however, associated with a projected gain in survival, resulting in overall lifetime cost effectiveness.

"In this extremely high-risk population, an elderly population, the intervention is adding roughly 2 years of life, and that is the return on investment," principal investigator Dr. Matthew Reynolds said during a press briefing at the annual meeting of the American College of Cardiology. "The cost-effectiveness ratio, when you do the math, works out to just over $50,000 per life-year gained."

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, said up-front hospital costs for TAVR will be high because of the need for a hybrid operative/interventional suite, but that as long as the risks and costs are reasonable, patients will opt for the percutaneous approach simply because they don’t want surgery.

During the formal study presentation, invited discussant Dr. Martyn Thomas, director of cardiovascular services at Guy’s and St. Thomas’ Hospitals, London, said clinicians in the United Kingdom were awaiting results of the cost analysis with bated breath to determine if TAVR could get the nod from the National Institute for Health and Clinical Excellence.

"When I plug in our numbers ... I get somewhere around £20,000 [U.S.$32,700] per QALY [quality-adjusted life-year], which for us would be absolutely perfect," Dr. Thomas said.

Anticipation regarding TAVR has been building since efficacy data reported last fall for the same 358 inoperable patients, known as cohort B, demonstrated a 20% survival benefit with TAVR at 1 year, compared with standard medical therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-6070).

The question, however, is whether the novel procedure will be cost effective in an increasingly heated climate of health care cost containment.

In an attempt to tackle the issue, Dr. Reynolds and his colleagues assessed lifetime incremental cost-effectiveness ratios (ICERs) and lifetime incremental costs per QALY using hospital billing data or MEDPAR when bills were unavailable. Costs from the last 6 months for surviving patients were used to project future costs beyond 12 months, while parametric survival models fit to the trial data were used to extrapolate patient-level life expectancy beyond the follow-up period.

The initial $78,540 price tag for TAVR includes $42,806 for procedural costs, $30,756 for nonprocedural expenses, and $4,978 for physician fees, said Dr. Reynolds, director of the Economics and Quality of Life Research Center at the Harvard Clinical Research Institute, Boston. Patients spent an average of 10 days in the hospital, including 4 days in the intensive care unit.

Twelve-month follow-up costs were $23,372 higher for patients treated with standard medical therapy. This was a result of significantly more hospitalizations in the control group than in the TAVR group (2.15 vs. 1.02), mainly due to cardiovascular causes (1.7 vs. 0.50), he said.

The estimated life expectancy was 3.1 years for patients treated with TAVR and 1.2 years for those treated with medical therapy, or a difference of 1.9 years.

The lifetime incremental cost per patient was $79,837, and the lifetime incremental gain in life expectancy was 1.59 years. This translated into an ICER of $50,212 per life-year gained and $61,889 per QALY, he said.

Additional analysis showed that if the price of the device were to drop to $20,000, the ICER would be $43,642 per life-year gained. In Europe, both the SAPIEN valve (Edwards Lifesciences) and the CoreValve (Medtronic) are already on the market.

On the basis of the data, TAVR in this older inoperable cohort falls very close to published cost-effectiveness estimates for implantable defibrillators and atrial fibrillation ablation, and is actually lower than current estimates for hemodialysis or percutaneous coronary intervention for stable coronary artery disease, Dr. Reynolds said.

"For patients with severe aortic stenosis who are unsuitable for surgical aortic valve replacement, TAVR significantly increases life expectancy at an incremental cost per life-year gained well within accepted values for commonly used cardiovascular technologies," he said.

When asked what the budget impact would be of adoption of TAVR, Dr. Reynolds said they have not performed such an analysis, but that an estimated 30% of patients with severe aortic stenosis do not undergo conventional open surgery.

Efficacy data presented at the same session by Dr. Craig Smith on cohort A of the PARTNER trial, revealed that all-cause mortality in 699 high-risk patients with severe aortic stenosis was the same at 1 year, at 24% with TAVR vs. 27% with conventional open surgery, but that the incidence of stroke was increased at 8.3% vs. 4.3%. Cost comparisons of TAVR vs. conventional surgery are not yet available.

Edwards Lifesciences provided grant support for the analysis.

NEW ORLEANS – The cost of transcatheter aortic valve replacement among patients with inoperable severe aortic stenosis is in line with other accepted cardiovascular procedures, according to an economic analysis of the PARTNER trial.

Index hospitalization costs for transcatheter aortic valve replacement (TAVR) were $78,540 based on an estimated cost of $30,000 for the investigational Edwards SAPIEN valve. TAVR was, however, associated with a projected gain in survival, resulting in overall lifetime cost effectiveness.

"In this extremely high-risk population, an elderly population, the intervention is adding roughly 2 years of life, and that is the return on investment," principal investigator Dr. Matthew Reynolds said during a press briefing at the annual meeting of the American College of Cardiology. "The cost-effectiveness ratio, when you do the math, works out to just over $50,000 per life-year gained."

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, said up-front hospital costs for TAVR will be high because of the need for a hybrid operative/interventional suite, but that as long as the risks and costs are reasonable, patients will opt for the percutaneous approach simply because they don’t want surgery.

During the formal study presentation, invited discussant Dr. Martyn Thomas, director of cardiovascular services at Guy’s and St. Thomas’ Hospitals, London, said clinicians in the United Kingdom were awaiting results of the cost analysis with bated breath to determine if TAVR could get the nod from the National Institute for Health and Clinical Excellence.

"When I plug in our numbers ... I get somewhere around £20,000 [U.S.$32,700] per QALY [quality-adjusted life-year], which for us would be absolutely perfect," Dr. Thomas said.

Anticipation regarding TAVR has been building since efficacy data reported last fall for the same 358 inoperable patients, known as cohort B, demonstrated a 20% survival benefit with TAVR at 1 year, compared with standard medical therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-6070).

The question, however, is whether the novel procedure will be cost effective in an increasingly heated climate of health care cost containment.

In an attempt to tackle the issue, Dr. Reynolds and his colleagues assessed lifetime incremental cost-effectiveness ratios (ICERs) and lifetime incremental costs per QALY using hospital billing data or MEDPAR when bills were unavailable. Costs from the last 6 months for surviving patients were used to project future costs beyond 12 months, while parametric survival models fit to the trial data were used to extrapolate patient-level life expectancy beyond the follow-up period.

The initial $78,540 price tag for TAVR includes $42,806 for procedural costs, $30,756 for nonprocedural expenses, and $4,978 for physician fees, said Dr. Reynolds, director of the Economics and Quality of Life Research Center at the Harvard Clinical Research Institute, Boston. Patients spent an average of 10 days in the hospital, including 4 days in the intensive care unit.

Twelve-month follow-up costs were $23,372 higher for patients treated with standard medical therapy. This was a result of significantly more hospitalizations in the control group than in the TAVR group (2.15 vs. 1.02), mainly due to cardiovascular causes (1.7 vs. 0.50), he said.

The estimated life expectancy was 3.1 years for patients treated with TAVR and 1.2 years for those treated with medical therapy, or a difference of 1.9 years.

The lifetime incremental cost per patient was $79,837, and the lifetime incremental gain in life expectancy was 1.59 years. This translated into an ICER of $50,212 per life-year gained and $61,889 per QALY, he said.

Additional analysis showed that if the price of the device were to drop to $20,000, the ICER would be $43,642 per life-year gained. In Europe, both the SAPIEN valve (Edwards Lifesciences) and the CoreValve (Medtronic) are already on the market.

On the basis of the data, TAVR in this older inoperable cohort falls very close to published cost-effectiveness estimates for implantable defibrillators and atrial fibrillation ablation, and is actually lower than current estimates for hemodialysis or percutaneous coronary intervention for stable coronary artery disease, Dr. Reynolds said.

"For patients with severe aortic stenosis who are unsuitable for surgical aortic valve replacement, TAVR significantly increases life expectancy at an incremental cost per life-year gained well within accepted values for commonly used cardiovascular technologies," he said.

When asked what the budget impact would be of adoption of TAVR, Dr. Reynolds said they have not performed such an analysis, but that an estimated 30% of patients with severe aortic stenosis do not undergo conventional open surgery.

Efficacy data presented at the same session by Dr. Craig Smith on cohort A of the PARTNER trial, revealed that all-cause mortality in 699 high-risk patients with severe aortic stenosis was the same at 1 year, at 24% with TAVR vs. 27% with conventional open surgery, but that the incidence of stroke was increased at 8.3% vs. 4.3%. Cost comparisons of TAVR vs. conventional surgery are not yet available.

Edwards Lifesciences provided grant support for the analysis.

NEW ORLEANS – The cost of transcatheter aortic valve replacement among patients with inoperable severe aortic stenosis is in line with other accepted cardiovascular procedures, according to an economic analysis of the PARTNER trial.

Index hospitalization costs for transcatheter aortic valve replacement (TAVR) were $78,540 based on an estimated cost of $30,000 for the investigational Edwards SAPIEN valve. TAVR was, however, associated with a projected gain in survival, resulting in overall lifetime cost effectiveness.

"In this extremely high-risk population, an elderly population, the intervention is adding roughly 2 years of life, and that is the return on investment," principal investigator Dr. Matthew Reynolds said during a press briefing at the annual meeting of the American College of Cardiology. "The cost-effectiveness ratio, when you do the math, works out to just over $50,000 per life-year gained."

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, said up-front hospital costs for TAVR will be high because of the need for a hybrid operative/interventional suite, but that as long as the risks and costs are reasonable, patients will opt for the percutaneous approach simply because they don’t want surgery.

During the formal study presentation, invited discussant Dr. Martyn Thomas, director of cardiovascular services at Guy’s and St. Thomas’ Hospitals, London, said clinicians in the United Kingdom were awaiting results of the cost analysis with bated breath to determine if TAVR could get the nod from the National Institute for Health and Clinical Excellence.

"When I plug in our numbers ... I get somewhere around £20,000 [U.S.$32,700] per QALY [quality-adjusted life-year], which for us would be absolutely perfect," Dr. Thomas said.

Anticipation regarding TAVR has been building since efficacy data reported last fall for the same 358 inoperable patients, known as cohort B, demonstrated a 20% survival benefit with TAVR at 1 year, compared with standard medical therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-6070).

The question, however, is whether the novel procedure will be cost effective in an increasingly heated climate of health care cost containment.

In an attempt to tackle the issue, Dr. Reynolds and his colleagues assessed lifetime incremental cost-effectiveness ratios (ICERs) and lifetime incremental costs per QALY using hospital billing data or MEDPAR when bills were unavailable. Costs from the last 6 months for surviving patients were used to project future costs beyond 12 months, while parametric survival models fit to the trial data were used to extrapolate patient-level life expectancy beyond the follow-up period.

The initial $78,540 price tag for TAVR includes $42,806 for procedural costs, $30,756 for nonprocedural expenses, and $4,978 for physician fees, said Dr. Reynolds, director of the Economics and Quality of Life Research Center at the Harvard Clinical Research Institute, Boston. Patients spent an average of 10 days in the hospital, including 4 days in the intensive care unit.

Twelve-month follow-up costs were $23,372 higher for patients treated with standard medical therapy. This was a result of significantly more hospitalizations in the control group than in the TAVR group (2.15 vs. 1.02), mainly due to cardiovascular causes (1.7 vs. 0.50), he said.

The estimated life expectancy was 3.1 years for patients treated with TAVR and 1.2 years for those treated with medical therapy, or a difference of 1.9 years.

The lifetime incremental cost per patient was $79,837, and the lifetime incremental gain in life expectancy was 1.59 years. This translated into an ICER of $50,212 per life-year gained and $61,889 per QALY, he said.

Additional analysis showed that if the price of the device were to drop to $20,000, the ICER would be $43,642 per life-year gained. In Europe, both the SAPIEN valve (Edwards Lifesciences) and the CoreValve (Medtronic) are already on the market.

On the basis of the data, TAVR in this older inoperable cohort falls very close to published cost-effectiveness estimates for implantable defibrillators and atrial fibrillation ablation, and is actually lower than current estimates for hemodialysis or percutaneous coronary intervention for stable coronary artery disease, Dr. Reynolds said.

"For patients with severe aortic stenosis who are unsuitable for surgical aortic valve replacement, TAVR significantly increases life expectancy at an incremental cost per life-year gained well within accepted values for commonly used cardiovascular technologies," he said.

When asked what the budget impact would be of adoption of TAVR, Dr. Reynolds said they have not performed such an analysis, but that an estimated 30% of patients with severe aortic stenosis do not undergo conventional open surgery.

Efficacy data presented at the same session by Dr. Craig Smith on cohort A of the PARTNER trial, revealed that all-cause mortality in 699 high-risk patients with severe aortic stenosis was the same at 1 year, at 24% with TAVR vs. 27% with conventional open surgery, but that the incidence of stroke was increased at 8.3% vs. 4.3%. Cost comparisons of TAVR vs. conventional surgery are not yet available.

Edwards Lifesciences provided grant support for the analysis.

NEW ORLEANS – The cost of transcatheter aortic valve replacement among patients with inoperable severe aortic stenosis is in line with other accepted cardiovascular procedures, according to an economic analysis of the PARTNER trial.

Index hospitalization costs for transcatheter aortic valve replacement (TAVR) were $78,540 based on an estimated cost of $30,000 for the investigational Edwards SAPIEN valve. TAVR was, however, associated with a projected gain in survival, resulting in overall lifetime cost effectiveness.

"In this extremely high-risk population, an elderly population, the intervention is adding roughly 2 years of life, and that is the return on investment," principal investigator Dr. Matthew Reynolds said during a press briefing at the annual meeting of the American College of Cardiology. "The cost-effectiveness ratio, when you do the math, works out to just over $50,000 per life-year gained."

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, said up-front hospital costs for TAVR will be high because of the need for a hybrid operative/interventional suite, but that as long as the risks and costs are reasonable, patients will opt for the percutaneous approach simply because they don’t want surgery.

During the formal study presentation, invited discussant Dr. Martyn Thomas, director of cardiovascular services at Guy’s and St. Thomas’ Hospitals, London, said clinicians in the United Kingdom were awaiting results of the cost analysis with bated breath to determine if TAVR could get the nod from the National Institute for Health and Clinical Excellence.

"When I plug in our numbers ... I get somewhere around £20,000 [U.S.$32,700] per QALY [quality-adjusted life-year], which for us would be absolutely perfect," Dr. Thomas said.

Anticipation regarding TAVR has been building since efficacy data reported last fall for the same 358 inoperable patients, known as cohort B, demonstrated a 20% survival benefit with TAVR at 1 year, compared with standard medical therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-6070).

The question, however, is whether the novel procedure will be cost effective in an increasingly heated climate of health care cost containment.

In an attempt to tackle the issue, Dr. Reynolds and his colleagues assessed lifetime incremental cost-effectiveness ratios (ICERs) and lifetime incremental costs per QALY using hospital billing data or MEDPAR when bills were unavailable. Costs from the last 6 months for surviving patients were used to project future costs beyond 12 months, while parametric survival models fit to the trial data were used to extrapolate patient-level life expectancy beyond the follow-up period.

The initial $78,540 price tag for TAVR includes $42,806 for procedural costs, $30,756 for nonprocedural expenses, and $4,978 for physician fees, said Dr. Reynolds, director of the Economics and Quality of Life Research Center at the Harvard Clinical Research Institute, Boston. Patients spent an average of 10 days in the hospital, including 4 days in the intensive care unit.

Twelve-month follow-up costs were $23,372 higher for patients treated with standard medical therapy. This was a result of significantly more hospitalizations in the control group than in the TAVR group (2.15 vs. 1.02), mainly due to cardiovascular causes (1.7 vs. 0.50), he said.

The estimated life expectancy was 3.1 years for patients treated with TAVR and 1.2 years for those treated with medical therapy, or a difference of 1.9 years.

The lifetime incremental cost per patient was $79,837, and the lifetime incremental gain in life expectancy was 1.59 years. This translated into an ICER of $50,212 per life-year gained and $61,889 per QALY, he said.

Additional analysis showed that if the price of the device were to drop to $20,000, the ICER would be $43,642 per life-year gained. In Europe, both the SAPIEN valve (Edwards Lifesciences) and the CoreValve (Medtronic) are already on the market.

On the basis of the data, TAVR in this older inoperable cohort falls very close to published cost-effectiveness estimates for implantable defibrillators and atrial fibrillation ablation, and is actually lower than current estimates for hemodialysis or percutaneous coronary intervention for stable coronary artery disease, Dr. Reynolds said.

"For patients with severe aortic stenosis who are unsuitable for surgical aortic valve replacement, TAVR significantly increases life expectancy at an incremental cost per life-year gained well within accepted values for commonly used cardiovascular technologies," he said.

When asked what the budget impact would be of adoption of TAVR, Dr. Reynolds said they have not performed such an analysis, but that an estimated 30% of patients with severe aortic stenosis do not undergo conventional open surgery.

Efficacy data presented at the same session by Dr. Craig Smith on cohort A of the PARTNER trial, revealed that all-cause mortality in 699 high-risk patients with severe aortic stenosis was the same at 1 year, at 24% with TAVR vs. 27% with conventional open surgery, but that the incidence of stroke was increased at 8.3% vs. 4.3%. Cost comparisons of TAVR vs. conventional surgery are not yet available.

Edwards Lifesciences provided grant support for the analysis.

NEW ORLEANS – The cost of transcatheter aortic valve replacement among patients with inoperable severe aortic stenosis is in line with other accepted cardiovascular procedures, according to an economic analysis of the PARTNER trial.

Index hospitalization costs for transcatheter aortic valve replacement (TAVR) were $78,540 based on an estimated cost of $30,000 for the investigational Edwards SAPIEN valve. TAVR was, however, associated with a projected gain in survival, resulting in overall lifetime cost effectiveness.

"In this extremely high-risk population, an elderly population, the intervention is adding roughly 2 years of life, and that is the return on investment," principal investigator Dr. Matthew Reynolds said during a press briefing at the annual meeting of the American College of Cardiology. "The cost-effectiveness ratio, when you do the math, works out to just over $50,000 per life-year gained."

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, said up-front hospital costs for TAVR will be high because of the need for a hybrid operative/interventional suite, but that as long as the risks and costs are reasonable, patients will opt for the percutaneous approach simply because they don’t want surgery.

During the formal study presentation, invited discussant Dr. Martyn Thomas, director of cardiovascular services at Guy’s and St. Thomas’ Hospitals, London, said clinicians in the United Kingdom were awaiting results of the cost analysis with bated breath to determine if TAVR could get the nod from the National Institute for Health and Clinical Excellence.

"When I plug in our numbers ... I get somewhere around £20,000 [U.S.$32,700] per QALY [quality-adjusted life-year], which for us would be absolutely perfect," Dr. Thomas said.

Anticipation regarding TAVR has been building since efficacy data reported last fall for the same 358 inoperable patients, known as cohort B, demonstrated a 20% survival benefit with TAVR at 1 year, compared with standard medical therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-6070).

The question, however, is whether the novel procedure will be cost effective in an increasingly heated climate of health care cost containment.

In an attempt to tackle the issue, Dr. Reynolds and his colleagues assessed lifetime incremental cost-effectiveness ratios (ICERs) and lifetime incremental costs per QALY using hospital billing data or MEDPAR when bills were unavailable. Costs from the last 6 months for surviving patients were used to project future costs beyond 12 months, while parametric survival models fit to the trial data were used to extrapolate patient-level life expectancy beyond the follow-up period.

The initial $78,540 price tag for TAVR includes $42,806 for procedural costs, $30,756 for nonprocedural expenses, and $4,978 for physician fees, said Dr. Reynolds, director of the Economics and Quality of Life Research Center at the Harvard Clinical Research Institute, Boston. Patients spent an average of 10 days in the hospital, including 4 days in the intensive care unit.

Twelve-month follow-up costs were $23,372 higher for patients treated with standard medical therapy. This was a result of significantly more hospitalizations in the control group than in the TAVR group (2.15 vs. 1.02), mainly due to cardiovascular causes (1.7 vs. 0.50), he said.

The estimated life expectancy was 3.1 years for patients treated with TAVR and 1.2 years for those treated with medical therapy, or a difference of 1.9 years.

The lifetime incremental cost per patient was $79,837, and the lifetime incremental gain in life expectancy was 1.59 years. This translated into an ICER of $50,212 per life-year gained and $61,889 per QALY, he said.

Additional analysis showed that if the price of the device were to drop to $20,000, the ICER would be $43,642 per life-year gained. In Europe, both the SAPIEN valve (Edwards Lifesciences) and the CoreValve (Medtronic) are already on the market.

On the basis of the data, TAVR in this older inoperable cohort falls very close to published cost-effectiveness estimates for implantable defibrillators and atrial fibrillation ablation, and is actually lower than current estimates for hemodialysis or percutaneous coronary intervention for stable coronary artery disease, Dr. Reynolds said.

"For patients with severe aortic stenosis who are unsuitable for surgical aortic valve replacement, TAVR significantly increases life expectancy at an incremental cost per life-year gained well within accepted values for commonly used cardiovascular technologies," he said.

When asked what the budget impact would be of adoption of TAVR, Dr. Reynolds said they have not performed such an analysis, but that an estimated 30% of patients with severe aortic stenosis do not undergo conventional open surgery.

Efficacy data presented at the same session by Dr. Craig Smith on cohort A of the PARTNER trial, revealed that all-cause mortality in 699 high-risk patients with severe aortic stenosis was the same at 1 year, at 24% with TAVR vs. 27% with conventional open surgery, but that the incidence of stroke was increased at 8.3% vs. 4.3%. Cost comparisons of TAVR vs. conventional surgery are not yet available.

Edwards Lifesciences provided grant support for the analysis.

NEW ORLEANS – The cost of transcatheter aortic valve replacement among patients with inoperable severe aortic stenosis is in line with other accepted cardiovascular procedures, according to an economic analysis of the PARTNER trial.

Index hospitalization costs for transcatheter aortic valve replacement (TAVR) were $78,540 based on an estimated cost of $30,000 for the investigational Edwards SAPIEN valve. TAVR was, however, associated with a projected gain in survival, resulting in overall lifetime cost effectiveness.

"In this extremely high-risk population, an elderly population, the intervention is adding roughly 2 years of life, and that is the return on investment," principal investigator Dr. Matthew Reynolds said during a press briefing at the annual meeting of the American College of Cardiology. "The cost-effectiveness ratio, when you do the math, works out to just over $50,000 per life-year gained."

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, said up-front hospital costs for TAVR will be high because of the need for a hybrid operative/interventional suite, but that as long as the risks and costs are reasonable, patients will opt for the percutaneous approach simply because they don’t want surgery.

During the formal study presentation, invited discussant Dr. Martyn Thomas, director of cardiovascular services at Guy’s and St. Thomas’ Hospitals, London, said clinicians in the United Kingdom were awaiting results of the cost analysis with bated breath to determine if TAVR could get the nod from the National Institute for Health and Clinical Excellence.

"When I plug in our numbers ... I get somewhere around £20,000 [U.S.$32,700] per QALY [quality-adjusted life-year], which for us would be absolutely perfect," Dr. Thomas said.

Anticipation regarding TAVR has been building since efficacy data reported last fall for the same 358 inoperable patients, known as cohort B, demonstrated a 20% survival benefit with TAVR at 1 year, compared with standard medical therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-6070).

The question, however, is whether the novel procedure will be cost effective in an increasingly heated climate of health care cost containment.

In an attempt to tackle the issue, Dr. Reynolds and his colleagues assessed lifetime incremental cost-effectiveness ratios (ICERs) and lifetime incremental costs per QALY using hospital billing data or MEDPAR when bills were unavailable. Costs from the last 6 months for surviving patients were used to project future costs beyond 12 months, while parametric survival models fit to the trial data were used to extrapolate patient-level life expectancy beyond the follow-up period.

The initial $78,540 price tag for TAVR includes $42,806 for procedural costs, $30,756 for nonprocedural expenses, and $4,978 for physician fees, said Dr. Reynolds, director of the Economics and Quality of Life Research Center at the Harvard Clinical Research Institute, Boston. Patients spent an average of 10 days in the hospital, including 4 days in the intensive care unit.

Twelve-month follow-up costs were $23,372 higher for patients treated with standard medical therapy. This was a result of significantly more hospitalizations in the control group than in the TAVR group (2.15 vs. 1.02), mainly due to cardiovascular causes (1.7 vs. 0.50), he said.

The estimated life expectancy was 3.1 years for patients treated with TAVR and 1.2 years for those treated with medical therapy, or a difference of 1.9 years.

The lifetime incremental cost per patient was $79,837, and the lifetime incremental gain in life expectancy was 1.59 years. This translated into an ICER of $50,212 per life-year gained and $61,889 per QALY, he said.

Additional analysis showed that if the price of the device were to drop to $20,000, the ICER would be $43,642 per life-year gained. In Europe, both the SAPIEN valve (Edwards Lifesciences) and the CoreValve (Medtronic) are already on the market.

On the basis of the data, TAVR in this older inoperable cohort falls very close to published cost-effectiveness estimates for implantable defibrillators and atrial fibrillation ablation, and is actually lower than current estimates for hemodialysis or percutaneous coronary intervention for stable coronary artery disease, Dr. Reynolds said.

"For patients with severe aortic stenosis who are unsuitable for surgical aortic valve replacement, TAVR significantly increases life expectancy at an incremental cost per life-year gained well within accepted values for commonly used cardiovascular technologies," he said.

When asked what the budget impact would be of adoption of TAVR, Dr. Reynolds said they have not performed such an analysis, but that an estimated 30% of patients with severe aortic stenosis do not undergo conventional open surgery.

Efficacy data presented at the same session by Dr. Craig Smith on cohort A of the PARTNER trial, revealed that all-cause mortality in 699 high-risk patients with severe aortic stenosis was the same at 1 year, at 24% with TAVR vs. 27% with conventional open surgery, but that the incidence of stroke was increased at 8.3% vs. 4.3%. Cost comparisons of TAVR vs. conventional surgery are not yet available.

Edwards Lifesciences provided grant support for the analysis.

NEW ORLEANS – The cost of transcatheter aortic valve replacement among patients with inoperable severe aortic stenosis is in line with other accepted cardiovascular procedures, according to an economic analysis of the PARTNER trial.

Index hospitalization costs for transcatheter aortic valve replacement (TAVR) were $78,540 based on an estimated cost of $30,000 for the investigational Edwards SAPIEN valve. TAVR was, however, associated with a projected gain in survival, resulting in overall lifetime cost effectiveness.

"In this extremely high-risk population, an elderly population, the intervention is adding roughly 2 years of life, and that is the return on investment," principal investigator Dr. Matthew Reynolds said during a press briefing at the annual meeting of the American College of Cardiology. "The cost-effectiveness ratio, when you do the math, works out to just over $50,000 per life-year gained."

Dr. Michael Crawford, chief of clinical cardiology at the University of California, San Francisco, said up-front hospital costs for TAVR will be high because of the need for a hybrid operative/interventional suite, but that as long as the risks and costs are reasonable, patients will opt for the percutaneous approach simply because they don’t want surgery.

During the formal study presentation, invited discussant Dr. Martyn Thomas, director of cardiovascular services at Guy’s and St. Thomas’ Hospitals, London, said clinicians in the United Kingdom were awaiting results of the cost analysis with bated breath to determine if TAVR could get the nod from the National Institute for Health and Clinical Excellence.

"When I plug in our numbers ... I get somewhere around £20,000 [U.S.$32,700] per QALY [quality-adjusted life-year], which for us would be absolutely perfect," Dr. Thomas said.

Anticipation regarding TAVR has been building since efficacy data reported last fall for the same 358 inoperable patients, known as cohort B, demonstrated a 20% survival benefit with TAVR at 1 year, compared with standard medical therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-6070).

The question, however, is whether the novel procedure will be cost effective in an increasingly heated climate of health care cost containment.

In an attempt to tackle the issue, Dr. Reynolds and his colleagues assessed lifetime incremental cost-effectiveness ratios (ICERs) and lifetime incremental costs per QALY using hospital billing data or MEDPAR when bills were unavailable. Costs from the last 6 months for surviving patients were used to project future costs beyond 12 months, while parametric survival models fit to the trial data were used to extrapolate patient-level life expectancy beyond the follow-up period.

The initial $78,540 price tag for TAVR includes $42,806 for procedural costs, $30,756 for nonprocedural expenses, and $4,978 for physician fees, said Dr. Reynolds, director of the Economics and Quality of Life Research Center at the Harvard Clinical Research Institute, Boston. Patients spent an average of 10 days in the hospital, including 4 days in the intensive care unit.

Twelve-month follow-up costs were $23,372 higher for patients treated with standard medical therapy. This was a result of significantly more hospitalizations in the control group than in the TAVR group (2.15 vs. 1.02), mainly due to cardiovascular causes (1.7 vs. 0.50), he said.

The estimated life expectancy was 3.1 years for patients treated with TAVR and 1.2 years for those treated with medical therapy, or a difference of 1.9 years.

The lifetime incremental cost per patient was $79,837, and the lifetime incremental gain in life expectancy was 1.59 years. This translated into an ICER of $50,212 per life-year gained and $61,889 per QALY, he said.

Additional analysis showed that if the price of the device were to drop to $20,000, the ICER would be $43,642 per life-year gained. In Europe, both the SAPIEN valve (Edwards Lifesciences) and the CoreValve (Medtronic) are already on the market.

On the basis of the data, TAVR in this older inoperable cohort falls very close to published cost-effectiveness estimates for implantable defibrillators and atrial fibrillation ablation, and is actually lower than current estimates for hemodialysis or percutaneous coronary intervention for stable coronary artery disease, Dr. Reynolds said.

"For patients with severe aortic stenosis who are unsuitable for surgical aortic valve replacement, TAVR significantly increases life expectancy at an incremental cost per life-year gained well within accepted values for commonly used cardiovascular technologies," he said.

When asked what the budget impact would be of adoption of TAVR, Dr. Reynolds said they have not performed such an analysis, but that an estimated 30% of patients with severe aortic stenosis do not undergo conventional open surgery.

Efficacy data presented at the same session by Dr. Craig Smith on cohort A of the PARTNER trial, revealed that all-cause mortality in 699 high-risk patients with severe aortic stenosis was the same at 1 year, at 24% with TAVR vs. 27% with conventional open surgery, but that the incidence of stroke was increased at 8.3% vs. 4.3%. Cost comparisons of TAVR vs. conventional surgery are not yet available.

Edwards Lifesciences provided grant support for the analysis.

NEW ORLEANS – The investigational oral anticoagulant rivaroxaban was as effective as injection enoxaparin in preventing venous thromboembolism at 10 days and superior at 35 days among critically ill hospitalized patients in the phase III MAGELLAN study.

Overall bleeding rates were low, at about 1%, but were significantly higher in patients receiving rivaroxaban across the entire study period, lead author Dr. Alexander T. Cohen said April 5 at the annual meeting of the American College of Cardiology.

"MAGELLAN confirms that there is a continued risk of VTE [venous thromboembolism] beyond the initial period of hospitalization, and I believe this is an important finding because the benchmark data said we should get a figure of 4%, and we got a figure of 5.7% at day 45," he said.

The study randomly assigned 8,101 patients hospitalized for an acute medical illness including heart failure, acute infectious disease, and acute respiratory insufficiency to oral rivaroxaban 10 mg daily for 35 days or subcutaneous enoxaparin 40 mg daily for 10 days plus placebo.

At day 10, the primary composite efficacy end point, defined as the cumulative incidence of asymptomatic proximal deep venous thromboembolism (DVT) detected by ultrasonography, symptomatic DVT, symptomatic nonfatal pulmonary embolism (PE), and VTE-related death, occurred in 2.7% of patients in both arms, reaching the prespecified noninferiority benchmark for day 10.

At 35 days, significantly fewer rivaroxaban patients experienced the primary efficacy end point, at 4.4% vs. 5.7% of patients in the enoxaparin arm, reaching the superiority end point for day 35. The absolute risk reduction was 1.3% and the relative risk reduction was 23%, said Dr. Cohen, who is with King’s College in London.

Clinically relevant bleeding occurred significantly more often in the rivaroxaban group than in the enoxaparin group from day 1 to 10 (2.8% vs. 1.2%), from day 1 to 35 (4.1% vs. 1.7%), and from day 11 to 35 (1.4% vs. 0.5%).

Among major bleeding events, a drop in hemoglobin of 2 g/dL or more was observed in 31 rivaroxaban patients and 10 enoxaparin patients, 2 or more units of blood were transfused in 34 and 8 patients, respectively, and critical site bleeds occurred in 9 and 4 patients, respectively.

Notably, seven rivaroxaban patients died of fatal bleeds, compared with only one enoxaparin patient. Overall, about 5% of patients in the trial died of all causes.

The net clinical benefit was 9.4% for rivaroxaban and 7.8% for enoxaparin. Based on the prespecified net clinical benefit analysis, Dr. Cohen acknowledged that a consistently positive benefit-risk balance was not seen among the cohort, but that they plan to conduct subgroup analyses to determine factors related to bleeding and to identify patients who might derive greater benefit from thromboprophylaxis with rivaroxaban.

He stressed that the study used a highly sensitive analysis of bleeding, such as a drop in hemoglobin of just 2 g/dL, and that even nosebleeds and bruising were counted in the risk-benefit analysis. When asked whether removal of these lesser bleeding events would result in a positive clinical benefit for rivaroxaban, Dr. Cohen said he was hesitant to speculate outside the trial’s prespecified outcome measures. When pressed further, he replied, "If we looked at a traditional risk-benefit analysis of major bleeds, then the picture swings back the other way. ... It would start to look more favorable toward rivaroxaban, but I have to stick to the study protocol."

When asked whether he had a theory as to why fatal bleeds occurred, Dr. Cohen pointed out that while there were 7 bleeding deaths with rivaroxaban and only 1 with enoxaparin, there were 30 PE-related deaths with enoxaparin and 19 with rivaroxaban.

"So we saved 11 lives from blood clots, if you want to [make that sort of analysis], and lost 6 lives through bleeding," he said.

In a separate interview, Dr. A. Michael Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research, said numerous studies have shown that the risk of DVT persists beyond the acute hospitalization period and that the ability to give rivaroxaban after patients are discharged is valuable.

"It’s a much more practical drug to send patients home on," he said in an interview. "Yes, you can train patients to inject themselves with enoxaparin, but it’s not well accepted in many cases."

Dr. Cohen reported financial ties with more than a dozen pharmaceutical companies, including Bayer (maker of rivaroxaban). Dr. Lincoff had no relevant disclosures.

NEW ORLEANS – The investigational oral anticoagulant rivaroxaban was as effective as injection enoxaparin in preventing venous thromboembolism at 10 days and superior at 35 days among critically ill hospitalized patients in the phase III MAGELLAN study.

Overall bleeding rates were low, at about 1%, but were significantly higher in patients receiving rivaroxaban across the entire study period, lead author Dr. Alexander T. Cohen said April 5 at the annual meeting of the American College of Cardiology.

"MAGELLAN confirms that there is a continued risk of VTE [venous thromboembolism] beyond the initial period of hospitalization, and I believe this is an important finding because the benchmark data said we should get a figure of 4%, and we got a figure of 5.7% at day 45," he said.

The study randomly assigned 8,101 patients hospitalized for an acute medical illness including heart failure, acute infectious disease, and acute respiratory insufficiency to oral rivaroxaban 10 mg daily for 35 days or subcutaneous enoxaparin 40 mg daily for 10 days plus placebo.

At day 10, the primary composite efficacy end point, defined as the cumulative incidence of asymptomatic proximal deep venous thromboembolism (DVT) detected by ultrasonography, symptomatic DVT, symptomatic nonfatal pulmonary embolism (PE), and VTE-related death, occurred in 2.7% of patients in both arms, reaching the prespecified noninferiority benchmark for day 10.

At 35 days, significantly fewer rivaroxaban patients experienced the primary efficacy end point, at 4.4% vs. 5.7% of patients in the enoxaparin arm, reaching the superiority end point for day 35. The absolute risk reduction was 1.3% and the relative risk reduction was 23%, said Dr. Cohen, who is with King’s College in London.

Clinically relevant bleeding occurred significantly more often in the rivaroxaban group than in the enoxaparin group from day 1 to 10 (2.8% vs. 1.2%), from day 1 to 35 (4.1% vs. 1.7%), and from day 11 to 35 (1.4% vs. 0.5%).

Among major bleeding events, a drop in hemoglobin of 2 g/dL or more was observed in 31 rivaroxaban patients and 10 enoxaparin patients, 2 or more units of blood were transfused in 34 and 8 patients, respectively, and critical site bleeds occurred in 9 and 4 patients, respectively.

Notably, seven rivaroxaban patients died of fatal bleeds, compared with only one enoxaparin patient. Overall, about 5% of patients in the trial died of all causes.

The net clinical benefit was 9.4% for rivaroxaban and 7.8% for enoxaparin. Based on the prespecified net clinical benefit analysis, Dr. Cohen acknowledged that a consistently positive benefit-risk balance was not seen among the cohort, but that they plan to conduct subgroup analyses to determine factors related to bleeding and to identify patients who might derive greater benefit from thromboprophylaxis with rivaroxaban.

He stressed that the study used a highly sensitive analysis of bleeding, such as a drop in hemoglobin of just 2 g/dL, and that even nosebleeds and bruising were counted in the risk-benefit analysis. When asked whether removal of these lesser bleeding events would result in a positive clinical benefit for rivaroxaban, Dr. Cohen said he was hesitant to speculate outside the trial’s prespecified outcome measures. When pressed further, he replied, "If we looked at a traditional risk-benefit analysis of major bleeds, then the picture swings back the other way. ... It would start to look more favorable toward rivaroxaban, but I have to stick to the study protocol."

When asked whether he had a theory as to why fatal bleeds occurred, Dr. Cohen pointed out that while there were 7 bleeding deaths with rivaroxaban and only 1 with enoxaparin, there were 30 PE-related deaths with enoxaparin and 19 with rivaroxaban.

"So we saved 11 lives from blood clots, if you want to [make that sort of analysis], and lost 6 lives through bleeding," he said.

In a separate interview, Dr. A. Michael Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research, said numerous studies have shown that the risk of DVT persists beyond the acute hospitalization period and that the ability to give rivaroxaban after patients are discharged is valuable.

"It’s a much more practical drug to send patients home on," he said in an interview. "Yes, you can train patients to inject themselves with enoxaparin, but it’s not well accepted in many cases."

Dr. Cohen reported financial ties with more than a dozen pharmaceutical companies, including Bayer (maker of rivaroxaban). Dr. Lincoff had no relevant disclosures.

NEW ORLEANS – The investigational oral anticoagulant rivaroxaban was as effective as injection enoxaparin in preventing venous thromboembolism at 10 days and superior at 35 days among critically ill hospitalized patients in the phase III MAGELLAN study.

Overall bleeding rates were low, at about 1%, but were significantly higher in patients receiving rivaroxaban across the entire study period, lead author Dr. Alexander T. Cohen said April 5 at the annual meeting of the American College of Cardiology.

"MAGELLAN confirms that there is a continued risk of VTE [venous thromboembolism] beyond the initial period of hospitalization, and I believe this is an important finding because the benchmark data said we should get a figure of 4%, and we got a figure of 5.7% at day 45," he said.

The study randomly assigned 8,101 patients hospitalized for an acute medical illness including heart failure, acute infectious disease, and acute respiratory insufficiency to oral rivaroxaban 10 mg daily for 35 days or subcutaneous enoxaparin 40 mg daily for 10 days plus placebo.

At day 10, the primary composite efficacy end point, defined as the cumulative incidence of asymptomatic proximal deep venous thromboembolism (DVT) detected by ultrasonography, symptomatic DVT, symptomatic nonfatal pulmonary embolism (PE), and VTE-related death, occurred in 2.7% of patients in both arms, reaching the prespecified noninferiority benchmark for day 10.

At 35 days, significantly fewer rivaroxaban patients experienced the primary efficacy end point, at 4.4% vs. 5.7% of patients in the enoxaparin arm, reaching the superiority end point for day 35. The absolute risk reduction was 1.3% and the relative risk reduction was 23%, said Dr. Cohen, who is with King’s College in London.

Clinically relevant bleeding occurred significantly more often in the rivaroxaban group than in the enoxaparin group from day 1 to 10 (2.8% vs. 1.2%), from day 1 to 35 (4.1% vs. 1.7%), and from day 11 to 35 (1.4% vs. 0.5%).

Among major bleeding events, a drop in hemoglobin of 2 g/dL or more was observed in 31 rivaroxaban patients and 10 enoxaparin patients, 2 or more units of blood were transfused in 34 and 8 patients, respectively, and critical site bleeds occurred in 9 and 4 patients, respectively.

Notably, seven rivaroxaban patients died of fatal bleeds, compared with only one enoxaparin patient. Overall, about 5% of patients in the trial died of all causes.

The net clinical benefit was 9.4% for rivaroxaban and 7.8% for enoxaparin. Based on the prespecified net clinical benefit analysis, Dr. Cohen acknowledged that a consistently positive benefit-risk balance was not seen among the cohort, but that they plan to conduct subgroup analyses to determine factors related to bleeding and to identify patients who might derive greater benefit from thromboprophylaxis with rivaroxaban.

He stressed that the study used a highly sensitive analysis of bleeding, such as a drop in hemoglobin of just 2 g/dL, and that even nosebleeds and bruising were counted in the risk-benefit analysis. When asked whether removal of these lesser bleeding events would result in a positive clinical benefit for rivaroxaban, Dr. Cohen said he was hesitant to speculate outside the trial’s prespecified outcome measures. When pressed further, he replied, "If we looked at a traditional risk-benefit analysis of major bleeds, then the picture swings back the other way. ... It would start to look more favorable toward rivaroxaban, but I have to stick to the study protocol."

When asked whether he had a theory as to why fatal bleeds occurred, Dr. Cohen pointed out that while there were 7 bleeding deaths with rivaroxaban and only 1 with enoxaparin, there were 30 PE-related deaths with enoxaparin and 19 with rivaroxaban.

"So we saved 11 lives from blood clots, if you want to [make that sort of analysis], and lost 6 lives through bleeding," he said.

In a separate interview, Dr. A. Michael Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research, said numerous studies have shown that the risk of DVT persists beyond the acute hospitalization period and that the ability to give rivaroxaban after patients are discharged is valuable.

"It’s a much more practical drug to send patients home on," he said in an interview. "Yes, you can train patients to inject themselves with enoxaparin, but it’s not well accepted in many cases."

Dr. Cohen reported financial ties with more than a dozen pharmaceutical companies, including Bayer (maker of rivaroxaban). Dr. Lincoff had no relevant disclosures.

NEW ORLEANS – The investigational oral anticoagulant rivaroxaban was as effective as injection enoxaparin in preventing venous thromboembolism at 10 days and superior at 35 days among critically ill hospitalized patients in the phase III MAGELLAN study.

Overall bleeding rates were low, at about 1%, but were significantly higher in patients receiving rivaroxaban across the entire study period, lead author Dr. Alexander T. Cohen said April 5 at the annual meeting of the American College of Cardiology.

"MAGELLAN confirms that there is a continued risk of VTE [venous thromboembolism] beyond the initial period of hospitalization, and I believe this is an important finding because the benchmark data said we should get a figure of 4%, and we got a figure of 5.7% at day 45," he said.

The study randomly assigned 8,101 patients hospitalized for an acute medical illness including heart failure, acute infectious disease, and acute respiratory insufficiency to oral rivaroxaban 10 mg daily for 35 days or subcutaneous enoxaparin 40 mg daily for 10 days plus placebo.

At day 10, the primary composite efficacy end point, defined as the cumulative incidence of asymptomatic proximal deep venous thromboembolism (DVT) detected by ultrasonography, symptomatic DVT, symptomatic nonfatal pulmonary embolism (PE), and VTE-related death, occurred in 2.7% of patients in both arms, reaching the prespecified noninferiority benchmark for day 10.

At 35 days, significantly fewer rivaroxaban patients experienced the primary efficacy end point, at 4.4% vs. 5.7% of patients in the enoxaparin arm, reaching the superiority end point for day 35. The absolute risk reduction was 1.3% and the relative risk reduction was 23%, said Dr. Cohen, who is with King’s College in London.

Clinically relevant bleeding occurred significantly more often in the rivaroxaban group than in the enoxaparin group from day 1 to 10 (2.8% vs. 1.2%), from day 1 to 35 (4.1% vs. 1.7%), and from day 11 to 35 (1.4% vs. 0.5%).

Among major bleeding events, a drop in hemoglobin of 2 g/dL or more was observed in 31 rivaroxaban patients and 10 enoxaparin patients, 2 or more units of blood were transfused in 34 and 8 patients, respectively, and critical site bleeds occurred in 9 and 4 patients, respectively.

Notably, seven rivaroxaban patients died of fatal bleeds, compared with only one enoxaparin patient. Overall, about 5% of patients in the trial died of all causes.

The net clinical benefit was 9.4% for rivaroxaban and 7.8% for enoxaparin. Based on the prespecified net clinical benefit analysis, Dr. Cohen acknowledged that a consistently positive benefit-risk balance was not seen among the cohort, but that they plan to conduct subgroup analyses to determine factors related to bleeding and to identify patients who might derive greater benefit from thromboprophylaxis with rivaroxaban.

He stressed that the study used a highly sensitive analysis of bleeding, such as a drop in hemoglobin of just 2 g/dL, and that even nosebleeds and bruising were counted in the risk-benefit analysis. When asked whether removal of these lesser bleeding events would result in a positive clinical benefit for rivaroxaban, Dr. Cohen said he was hesitant to speculate outside the trial’s prespecified outcome measures. When pressed further, he replied, "If we looked at a traditional risk-benefit analysis of major bleeds, then the picture swings back the other way. ... It would start to look more favorable toward rivaroxaban, but I have to stick to the study protocol."

When asked whether he had a theory as to why fatal bleeds occurred, Dr. Cohen pointed out that while there were 7 bleeding deaths with rivaroxaban and only 1 with enoxaparin, there were 30 PE-related deaths with enoxaparin and 19 with rivaroxaban.

"So we saved 11 lives from blood clots, if you want to [make that sort of analysis], and lost 6 lives through bleeding," he said.

In a separate interview, Dr. A. Michael Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research, said numerous studies have shown that the risk of DVT persists beyond the acute hospitalization period and that the ability to give rivaroxaban after patients are discharged is valuable.

"It’s a much more practical drug to send patients home on," he said in an interview. "Yes, you can train patients to inject themselves with enoxaparin, but it’s not well accepted in many cases."

Dr. Cohen reported financial ties with more than a dozen pharmaceutical companies, including Bayer (maker of rivaroxaban). Dr. Lincoff had no relevant disclosures.

NEW ORLEANS – The investigational oral anticoagulant rivaroxaban was as effective as injection enoxaparin in preventing venous thromboembolism at 10 days and superior at 35 days among critically ill hospitalized patients in the phase III MAGELLAN study.

Overall bleeding rates were low, at about 1%, but were significantly higher in patients receiving rivaroxaban across the entire study period, lead author Dr. Alexander T. Cohen said April 5 at the annual meeting of the American College of Cardiology.

"MAGELLAN confirms that there is a continued risk of VTE [venous thromboembolism] beyond the initial period of hospitalization, and I believe this is an important finding because the benchmark data said we should get a figure of 4%, and we got a figure of 5.7% at day 45," he said.

The study randomly assigned 8,101 patients hospitalized for an acute medical illness including heart failure, acute infectious disease, and acute respiratory insufficiency to oral rivaroxaban 10 mg daily for 35 days or subcutaneous enoxaparin 40 mg daily for 10 days plus placebo.

At day 10, the primary composite efficacy end point, defined as the cumulative incidence of asymptomatic proximal deep venous thromboembolism (DVT) detected by ultrasonography, symptomatic DVT, symptomatic nonfatal pulmonary embolism (PE), and VTE-related death, occurred in 2.7% of patients in both arms, reaching the prespecified noninferiority benchmark for day 10.

At 35 days, significantly fewer rivaroxaban patients experienced the primary efficacy end point, at 4.4% vs. 5.7% of patients in the enoxaparin arm, reaching the superiority end point for day 35. The absolute risk reduction was 1.3% and the relative risk reduction was 23%, said Dr. Cohen, who is with King’s College in London.

Clinically relevant bleeding occurred significantly more often in the rivaroxaban group than in the enoxaparin group from day 1 to 10 (2.8% vs. 1.2%), from day 1 to 35 (4.1% vs. 1.7%), and from day 11 to 35 (1.4% vs. 0.5%).

Among major bleeding events, a drop in hemoglobin of 2 g/dL or more was observed in 31 rivaroxaban patients and 10 enoxaparin patients, 2 or more units of blood were transfused in 34 and 8 patients, respectively, and critical site bleeds occurred in 9 and 4 patients, respectively.

Notably, seven rivaroxaban patients died of fatal bleeds, compared with only one enoxaparin patient. Overall, about 5% of patients in the trial died of all causes.

The net clinical benefit was 9.4% for rivaroxaban and 7.8% for enoxaparin. Based on the prespecified net clinical benefit analysis, Dr. Cohen acknowledged that a consistently positive benefit-risk balance was not seen among the cohort, but that they plan to conduct subgroup analyses to determine factors related to bleeding and to identify patients who might derive greater benefit from thromboprophylaxis with rivaroxaban.

He stressed that the study used a highly sensitive analysis of bleeding, such as a drop in hemoglobin of just 2 g/dL, and that even nosebleeds and bruising were counted in the risk-benefit analysis. When asked whether removal of these lesser bleeding events would result in a positive clinical benefit for rivaroxaban, Dr. Cohen said he was hesitant to speculate outside the trial’s prespecified outcome measures. When pressed further, he replied, "If we looked at a traditional risk-benefit analysis of major bleeds, then the picture swings back the other way. ... It would start to look more favorable toward rivaroxaban, but I have to stick to the study protocol."

When asked whether he had a theory as to why fatal bleeds occurred, Dr. Cohen pointed out that while there were 7 bleeding deaths with rivaroxaban and only 1 with enoxaparin, there were 30 PE-related deaths with enoxaparin and 19 with rivaroxaban.

"So we saved 11 lives from blood clots, if you want to [make that sort of analysis], and lost 6 lives through bleeding," he said.

In a separate interview, Dr. A. Michael Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research, said numerous studies have shown that the risk of DVT persists beyond the acute hospitalization period and that the ability to give rivaroxaban after patients are discharged is valuable.

"It’s a much more practical drug to send patients home on," he said in an interview. "Yes, you can train patients to inject themselves with enoxaparin, but it’s not well accepted in many cases."

Dr. Cohen reported financial ties with more than a dozen pharmaceutical companies, including Bayer (maker of rivaroxaban). Dr. Lincoff had no relevant disclosures.

NEW ORLEANS – The investigational oral anticoagulant rivaroxaban was as effective as injection enoxaparin in preventing venous thromboembolism at 10 days and superior at 35 days among critically ill hospitalized patients in the phase III MAGELLAN study.

Overall bleeding rates were low, at about 1%, but were significantly higher in patients receiving rivaroxaban across the entire study period, lead author Dr. Alexander T. Cohen said April 5 at the annual meeting of the American College of Cardiology.

"MAGELLAN confirms that there is a continued risk of VTE [venous thromboembolism] beyond the initial period of hospitalization, and I believe this is an important finding because the benchmark data said we should get a figure of 4%, and we got a figure of 5.7% at day 45," he said.

The study randomly assigned 8,101 patients hospitalized for an acute medical illness including heart failure, acute infectious disease, and acute respiratory insufficiency to oral rivaroxaban 10 mg daily for 35 days or subcutaneous enoxaparin 40 mg daily for 10 days plus placebo.

At day 10, the primary composite efficacy end point, defined as the cumulative incidence of asymptomatic proximal deep venous thromboembolism (DVT) detected by ultrasonography, symptomatic DVT, symptomatic nonfatal pulmonary embolism (PE), and VTE-related death, occurred in 2.7% of patients in both arms, reaching the prespecified noninferiority benchmark for day 10.

At 35 days, significantly fewer rivaroxaban patients experienced the primary efficacy end point, at 4.4% vs. 5.7% of patients in the enoxaparin arm, reaching the superiority end point for day 35. The absolute risk reduction was 1.3% and the relative risk reduction was 23%, said Dr. Cohen, who is with King’s College in London.

Clinically relevant bleeding occurred significantly more often in the rivaroxaban group than in the enoxaparin group from day 1 to 10 (2.8% vs. 1.2%), from day 1 to 35 (4.1% vs. 1.7%), and from day 11 to 35 (1.4% vs. 0.5%).

Among major bleeding events, a drop in hemoglobin of 2 g/dL or more was observed in 31 rivaroxaban patients and 10 enoxaparin patients, 2 or more units of blood were transfused in 34 and 8 patients, respectively, and critical site bleeds occurred in 9 and 4 patients, respectively.

Notably, seven rivaroxaban patients died of fatal bleeds, compared with only one enoxaparin patient. Overall, about 5% of patients in the trial died of all causes.

The net clinical benefit was 9.4% for rivaroxaban and 7.8% for enoxaparin. Based on the prespecified net clinical benefit analysis, Dr. Cohen acknowledged that a consistently positive benefit-risk balance was not seen among the cohort, but that they plan to conduct subgroup analyses to determine factors related to bleeding and to identify patients who might derive greater benefit from thromboprophylaxis with rivaroxaban.

He stressed that the study used a highly sensitive analysis of bleeding, such as a drop in hemoglobin of just 2 g/dL, and that even nosebleeds and bruising were counted in the risk-benefit analysis. When asked whether removal of these lesser bleeding events would result in a positive clinical benefit for rivaroxaban, Dr. Cohen said he was hesitant to speculate outside the trial’s prespecified outcome measures. When pressed further, he replied, "If we looked at a traditional risk-benefit analysis of major bleeds, then the picture swings back the other way. ... It would start to look more favorable toward rivaroxaban, but I have to stick to the study protocol."

When asked whether he had a theory as to why fatal bleeds occurred, Dr. Cohen pointed out that while there were 7 bleeding deaths with rivaroxaban and only 1 with enoxaparin, there were 30 PE-related deaths with enoxaparin and 19 with rivaroxaban.

"So we saved 11 lives from blood clots, if you want to [make that sort of analysis], and lost 6 lives through bleeding," he said.

In a separate interview, Dr. A. Michael Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research, said numerous studies have shown that the risk of DVT persists beyond the acute hospitalization period and that the ability to give rivaroxaban after patients are discharged is valuable.

"It’s a much more practical drug to send patients home on," he said in an interview. "Yes, you can train patients to inject themselves with enoxaparin, but it’s not well accepted in many cases."

Dr. Cohen reported financial ties with more than a dozen pharmaceutical companies, including Bayer (maker of rivaroxaban). Dr. Lincoff had no relevant disclosures.

NEW ORLEANS – The investigational oral anticoagulant rivaroxaban was as effective as injection enoxaparin in preventing venous thromboembolism at 10 days and superior at 35 days among critically ill hospitalized patients in the phase III MAGELLAN study.

Overall bleeding rates were low, at about 1%, but were significantly higher in patients receiving rivaroxaban across the entire study period, lead author Dr. Alexander T. Cohen said April 5 at the annual meeting of the American College of Cardiology.

"MAGELLAN confirms that there is a continued risk of VTE [venous thromboembolism] beyond the initial period of hospitalization, and I believe this is an important finding because the benchmark data said we should get a figure of 4%, and we got a figure of 5.7% at day 45," he said.

The study randomly assigned 8,101 patients hospitalized for an acute medical illness including heart failure, acute infectious disease, and acute respiratory insufficiency to oral rivaroxaban 10 mg daily for 35 days or subcutaneous enoxaparin 40 mg daily for 10 days plus placebo.

At day 10, the primary composite efficacy end point, defined as the cumulative incidence of asymptomatic proximal deep venous thromboembolism (DVT) detected by ultrasonography, symptomatic DVT, symptomatic nonfatal pulmonary embolism (PE), and VTE-related death, occurred in 2.7% of patients in both arms, reaching the prespecified noninferiority benchmark for day 10.

At 35 days, significantly fewer rivaroxaban patients experienced the primary efficacy end point, at 4.4% vs. 5.7% of patients in the enoxaparin arm, reaching the superiority end point for day 35. The absolute risk reduction was 1.3% and the relative risk reduction was 23%, said Dr. Cohen, who is with King’s College in London.

Clinically relevant bleeding occurred significantly more often in the rivaroxaban group than in the enoxaparin group from day 1 to 10 (2.8% vs. 1.2%), from day 1 to 35 (4.1% vs. 1.7%), and from day 11 to 35 (1.4% vs. 0.5%).

Among major bleeding events, a drop in hemoglobin of 2 g/dL or more was observed in 31 rivaroxaban patients and 10 enoxaparin patients, 2 or more units of blood were transfused in 34 and 8 patients, respectively, and critical site bleeds occurred in 9 and 4 patients, respectively.

Notably, seven rivaroxaban patients died of fatal bleeds, compared with only one enoxaparin patient. Overall, about 5% of patients in the trial died of all causes.

The net clinical benefit was 9.4% for rivaroxaban and 7.8% for enoxaparin. Based on the prespecified net clinical benefit analysis, Dr. Cohen acknowledged that a consistently positive benefit-risk balance was not seen among the cohort, but that they plan to conduct subgroup analyses to determine factors related to bleeding and to identify patients who might derive greater benefit from thromboprophylaxis with rivaroxaban.

He stressed that the study used a highly sensitive analysis of bleeding, such as a drop in hemoglobin of just 2 g/dL, and that even nosebleeds and bruising were counted in the risk-benefit analysis. When asked whether removal of these lesser bleeding events would result in a positive clinical benefit for rivaroxaban, Dr. Cohen said he was hesitant to speculate outside the trial’s prespecified outcome measures. When pressed further, he replied, "If we looked at a traditional risk-benefit analysis of major bleeds, then the picture swings back the other way. ... It would start to look more favorable toward rivaroxaban, but I have to stick to the study protocol."

When asked whether he had a theory as to why fatal bleeds occurred, Dr. Cohen pointed out that while there were 7 bleeding deaths with rivaroxaban and only 1 with enoxaparin, there were 30 PE-related deaths with enoxaparin and 19 with rivaroxaban.

"So we saved 11 lives from blood clots, if you want to [make that sort of analysis], and lost 6 lives through bleeding," he said.

In a separate interview, Dr. A. Michael Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research, said numerous studies have shown that the risk of DVT persists beyond the acute hospitalization period and that the ability to give rivaroxaban after patients are discharged is valuable.

"It’s a much more practical drug to send patients home on," he said in an interview. "Yes, you can train patients to inject themselves with enoxaparin, but it’s not well accepted in many cases."

Dr. Cohen reported financial ties with more than a dozen pharmaceutical companies, including Bayer (maker of rivaroxaban). Dr. Lincoff had no relevant disclosures.

NEW ORLEANS – The investigational oral anticoagulant rivaroxaban was as effective as injection enoxaparin in preventing venous thromboembolism at 10 days and superior at 35 days among critically ill hospitalized patients in the phase III MAGELLAN study.

Overall bleeding rates were low, at about 1%, but were significantly higher in patients receiving rivaroxaban across the entire study period, lead author Dr. Alexander T. Cohen said April 5 at the annual meeting of the American College of Cardiology.

"MAGELLAN confirms that there is a continued risk of VTE [venous thromboembolism] beyond the initial period of hospitalization, and I believe this is an important finding because the benchmark data said we should get a figure of 4%, and we got a figure of 5.7% at day 45," he said.

The study randomly assigned 8,101 patients hospitalized for an acute medical illness including heart failure, acute infectious disease, and acute respiratory insufficiency to oral rivaroxaban 10 mg daily for 35 days or subcutaneous enoxaparin 40 mg daily for 10 days plus placebo.

At day 10, the primary composite efficacy end point, defined as the cumulative incidence of asymptomatic proximal deep venous thromboembolism (DVT) detected by ultrasonography, symptomatic DVT, symptomatic nonfatal pulmonary embolism (PE), and VTE-related death, occurred in 2.7% of patients in both arms, reaching the prespecified noninferiority benchmark for day 10.

At 35 days, significantly fewer rivaroxaban patients experienced the primary efficacy end point, at 4.4% vs. 5.7% of patients in the enoxaparin arm, reaching the superiority end point for day 35. The absolute risk reduction was 1.3% and the relative risk reduction was 23%, said Dr. Cohen, who is with King’s College in London.

Clinically relevant bleeding occurred significantly more often in the rivaroxaban group than in the enoxaparin group from day 1 to 10 (2.8% vs. 1.2%), from day 1 to 35 (4.1% vs. 1.7%), and from day 11 to 35 (1.4% vs. 0.5%).

Among major bleeding events, a drop in hemoglobin of 2 g/dL or more was observed in 31 rivaroxaban patients and 10 enoxaparin patients, 2 or more units of blood were transfused in 34 and 8 patients, respectively, and critical site bleeds occurred in 9 and 4 patients, respectively.

Notably, seven rivaroxaban patients died of fatal bleeds, compared with only one enoxaparin patient. Overall, about 5% of patients in the trial died of all causes.

The net clinical benefit was 9.4% for rivaroxaban and 7.8% for enoxaparin. Based on the prespecified net clinical benefit analysis, Dr. Cohen acknowledged that a consistently positive benefit-risk balance was not seen among the cohort, but that they plan to conduct subgroup analyses to determine factors related to bleeding and to identify patients who might derive greater benefit from thromboprophylaxis with rivaroxaban.

He stressed that the study used a highly sensitive analysis of bleeding, such as a drop in hemoglobin of just 2 g/dL, and that even nosebleeds and bruising were counted in the risk-benefit analysis. When asked whether removal of these lesser bleeding events would result in a positive clinical benefit for rivaroxaban, Dr. Cohen said he was hesitant to speculate outside the trial’s prespecified outcome measures. When pressed further, he replied, "If we looked at a traditional risk-benefit analysis of major bleeds, then the picture swings back the other way. ... It would start to look more favorable toward rivaroxaban, but I have to stick to the study protocol."

When asked whether he had a theory as to why fatal bleeds occurred, Dr. Cohen pointed out that while there were 7 bleeding deaths with rivaroxaban and only 1 with enoxaparin, there were 30 PE-related deaths with enoxaparin and 19 with rivaroxaban.

"So we saved 11 lives from blood clots, if you want to [make that sort of analysis], and lost 6 lives through bleeding," he said.

In a separate interview, Dr. A. Michael Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research, said numerous studies have shown that the risk of DVT persists beyond the acute hospitalization period and that the ability to give rivaroxaban after patients are discharged is valuable.

"It’s a much more practical drug to send patients home on," he said in an interview. "Yes, you can train patients to inject themselves with enoxaparin, but it’s not well accepted in many cases."

Dr. Cohen reported financial ties with more than a dozen pharmaceutical companies, including Bayer (maker of rivaroxaban). Dr. Lincoff had no relevant disclosures.

NEW ORLEANS – The investigational oral anticoagulant rivaroxaban was as effective as injection enoxaparin in preventing venous thromboembolism at 10 days and superior at 35 days among critically ill hospitalized patients in the phase III MAGELLAN study.

Overall bleeding rates were low, at about 1%, but were significantly higher in patients receiving rivaroxaban across the entire study period, lead author Dr. Alexander T. Cohen said April 5 at the annual meeting of the American College of Cardiology.

"MAGELLAN confirms that there is a continued risk of VTE [venous thromboembolism] beyond the initial period of hospitalization, and I believe this is an important finding because the benchmark data said we should get a figure of 4%, and we got a figure of 5.7% at day 45," he said.

The study randomly assigned 8,101 patients hospitalized for an acute medical illness including heart failure, acute infectious disease, and acute respiratory insufficiency to oral rivaroxaban 10 mg daily for 35 days or subcutaneous enoxaparin 40 mg daily for 10 days plus placebo.

At day 10, the primary composite efficacy end point, defined as the cumulative incidence of asymptomatic proximal deep venous thromboembolism (DVT) detected by ultrasonography, symptomatic DVT, symptomatic nonfatal pulmonary embolism (PE), and VTE-related death, occurred in 2.7% of patients in both arms, reaching the prespecified noninferiority benchmark for day 10.

At 35 days, significantly fewer rivaroxaban patients experienced the primary efficacy end point, at 4.4% vs. 5.7% of patients in the enoxaparin arm, reaching the superiority end point for day 35. The absolute risk reduction was 1.3% and the relative risk reduction was 23%, said Dr. Cohen, who is with King’s College in London.

Clinically relevant bleeding occurred significantly more often in the rivaroxaban group than in the enoxaparin group from day 1 to 10 (2.8% vs. 1.2%), from day 1 to 35 (4.1% vs. 1.7%), and from day 11 to 35 (1.4% vs. 0.5%).

Among major bleeding events, a drop in hemoglobin of 2 g/dL or more was observed in 31 rivaroxaban patients and 10 enoxaparin patients, 2 or more units of blood were transfused in 34 and 8 patients, respectively, and critical site bleeds occurred in 9 and 4 patients, respectively.

Notably, seven rivaroxaban patients died of fatal bleeds, compared with only one enoxaparin patient. Overall, about 5% of patients in the trial died of all causes.

The net clinical benefit was 9.4% for rivaroxaban and 7.8% for enoxaparin. Based on the prespecified net clinical benefit analysis, Dr. Cohen acknowledged that a consistently positive benefit-risk balance was not seen among the cohort, but that they plan to conduct subgroup analyses to determine factors related to bleeding and to identify patients who might derive greater benefit from thromboprophylaxis with rivaroxaban.

He stressed that the study used a highly sensitive analysis of bleeding, such as a drop in hemoglobin of just 2 g/dL, and that even nosebleeds and bruising were counted in the risk-benefit analysis. When asked whether removal of these lesser bleeding events would result in a positive clinical benefit for rivaroxaban, Dr. Cohen said he was hesitant to speculate outside the trial’s prespecified outcome measures. When pressed further, he replied, "If we looked at a traditional risk-benefit analysis of major bleeds, then the picture swings back the other way. ... It would start to look more favorable toward rivaroxaban, but I have to stick to the study protocol."

When asked whether he had a theory as to why fatal bleeds occurred, Dr. Cohen pointed out that while there were 7 bleeding deaths with rivaroxaban and only 1 with enoxaparin, there were 30 PE-related deaths with enoxaparin and 19 with rivaroxaban.

"So we saved 11 lives from blood clots, if you want to [make that sort of analysis], and lost 6 lives through bleeding," he said.

In a separate interview, Dr. A. Michael Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research, said numerous studies have shown that the risk of DVT persists beyond the acute hospitalization period and that the ability to give rivaroxaban after patients are discharged is valuable.

"It’s a much more practical drug to send patients home on," he said in an interview. "Yes, you can train patients to inject themselves with enoxaparin, but it’s not well accepted in many cases."

Dr. Cohen reported financial ties with more than a dozen pharmaceutical companies, including Bayer (maker of rivaroxaban). Dr. Lincoff had no relevant disclosures.

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.