Patrice Wendling

CHICAGO – Nonsurgical approaches are beginning to dominate the management of acute esophageal perforations.

An analysis of 81 consecutive acute esophageal perforation cases between June 1989 and March 2009 revealed that nonsurgical management jumped from 0% during the first 4 years of the study to 75% in the last 4 years (P value less than .001).

The average length of stay declined significantly over the same period, from 26 days to 20 days (P less than .001), while complications trended downward from 50% vs. 33%, Dr. Michal Hubka reported on behalf of lead author Dr. Madhan Kumar Kuppusamy and their colleagues at Virginia Mason Medical Center in Seattle.

In all, 33 patients were managed nonoperatively and 48 surgically. Primary repair was the most common surgical approach (34 cases). Nonsurgical treatments included endoscopic stenting (11 cases), drainage procedures including mediastinal drainage (13 cases), total parenteral nutrition (7 cases), Dobhoff feeding tube (5 cases), gastrostomy (5 cases), endoscopic repair with clips or glue (3 cases), and feeding jejunostomy (3 cases).

"Nonoperative treatment options are increasing and surgeons must be able to apply these techniques to improve outcomes," Dr. Hubka said at the annual meeting of the Western Surgical Association.

Hybrid-type management was performed in 21% of patients, and most often took the form of endoscopic stents or drainage at the time of open or thorascopic drainage or decortication.

The nonoperative group was less likely than the operative group to experience pneumonia (4 patients vs. 7 patients) and dysrhythmias (4 patients vs. 11 patients), but more likely to experience persistent leak at the 14th day (3 vs. 2), stent migration (3 vs. 0), sepsis (1 vs. 0), and renal failure (1 vs. 0), Dr. Hubka said. Deep vein thrombosis occurred in one patient in each group.

Two patients managed medically died vs. one treated surgically (6% vs. 2%), for an overall mortality rate of 3.7%. A historical comparison of nine other studies involving nonoperative management of esophageal perforations presented by Dr. Hubka showed mortality rates reaching a high of 24% between 1973 and 1993 and a low of 3.8% between 1990 and 2001.

One of those nine studies identified a stepwise increase in mortality as time from perforation to diagnosis increased, with 5% of 75 patients dying with an immediate diagnosis vs. 14% with a diagnosis within 24 hours and 44% if the diagnosis occurred after 24 hours (Eur. J. Cardiothorac. Surg. 2003;23:799-804).

In all, 57 patients in the current analysis were treated within 24 hours and 24 were treated after 24 hours. Length of stay was significantly shorter in the early-treatment group at 15.6 days vs. 29.4 days in the late-treatment group; however, complications (20 vs. 11) and mortality (1 vs. 2) were similar, Dr. Hubka said.

"Time to diagnosis continues to be important; however, management in an experienced center facile with all current management techniques is the major issue affecting outcomes," he said.

The percentage of cases referred to the tertiary referral center was 50% from 1989 to 1992 and 79% from 2005 to 2009. Referred patients were significantly more likely to be treated more than 24 hours after perforation.

The improvement in outcomes is likely related to increasing diversity of treatment techniques and management in specialty centers, Dr. Hubka said.

Invited discussant Dr. Jeffrey Peters from the University of Rochester (N. Y.) Medical Center said, "What you heard was an increasing chorus of a paradigm change, if you will, that’s sort of paradoxical to most of us – that someone with a hole in their esophagus does better if you don’t operate on them. I still struggle trying not to do that when patients present in the emergency room with these issues."

Still, he described the improvement in outcomes as true progress for patients. Dr. Peters noted that the etiology of acute perforations has changed over time, with most now iatrogenic, and thus the benefit of early treatment may not be as critical as in years past. He said referral to a tertiary center is important, but that the paper did not prove a causal effect.

Based on the findings, Dr. Peters asked when surgeons should operate, how the size of the injury and presence of underlying disease should be taken into account in treatment decisions, and when surgery should be considered if nonoperative therapy fails.

Dr. Hubka said patients with larger esophageal tears or injuries and moderate mediastinal pleural contamination who can tolerate surgery are the ones who proceed to the operating room. He suggested that the study’s operative rate would likely have been higher if patients with perforations due to neoplasia or cancer had been included and that the presence of such underlying disease would surely push them toward operative management in clinical practice. Finally, if a patient becomes unstable or their level of contamination increases despite nonsurgical management, they would proceed to surgery and decontamination.

"A point of our study is that this management, whether it’s endoscopic or operative, should be performed by surgeons because we have all the tools to manage all patients appropriately," Dr. Hubka said.

The study authors and discussant said that they had no financial disclosures.

CHICAGO – Nonsurgical approaches are beginning to dominate the management of acute esophageal perforations.

An analysis of 81 consecutive acute esophageal perforation cases between June 1989 and March 2009 revealed that nonsurgical management jumped from 0% during the first 4 years of the study to 75% in the last 4 years (P value less than .001).

The average length of stay declined significantly over the same period, from 26 days to 20 days (P less than .001), while complications trended downward from 50% vs. 33%, Dr. Michal Hubka reported on behalf of lead author Dr. Madhan Kumar Kuppusamy and their colleagues at Virginia Mason Medical Center in Seattle.

In all, 33 patients were managed nonoperatively and 48 surgically. Primary repair was the most common surgical approach (34 cases). Nonsurgical treatments included endoscopic stenting (11 cases), drainage procedures including mediastinal drainage (13 cases), total parenteral nutrition (7 cases), Dobhoff feeding tube (5 cases), gastrostomy (5 cases), endoscopic repair with clips or glue (3 cases), and feeding jejunostomy (3 cases).

"Nonoperative treatment options are increasing and surgeons must be able to apply these techniques to improve outcomes," Dr. Hubka said at the annual meeting of the Western Surgical Association.

Hybrid-type management was performed in 21% of patients, and most often took the form of endoscopic stents or drainage at the time of open or thorascopic drainage or decortication.

The nonoperative group was less likely than the operative group to experience pneumonia (4 patients vs. 7 patients) and dysrhythmias (4 patients vs. 11 patients), but more likely to experience persistent leak at the 14th day (3 vs. 2), stent migration (3 vs. 0), sepsis (1 vs. 0), and renal failure (1 vs. 0), Dr. Hubka said. Deep vein thrombosis occurred in one patient in each group.

Two patients managed medically died vs. one treated surgically (6% vs. 2%), for an overall mortality rate of 3.7%. A historical comparison of nine other studies involving nonoperative management of esophageal perforations presented by Dr. Hubka showed mortality rates reaching a high of 24% between 1973 and 1993 and a low of 3.8% between 1990 and 2001.

One of those nine studies identified a stepwise increase in mortality as time from perforation to diagnosis increased, with 5% of 75 patients dying with an immediate diagnosis vs. 14% with a diagnosis within 24 hours and 44% if the diagnosis occurred after 24 hours (Eur. J. Cardiothorac. Surg. 2003;23:799-804).

In all, 57 patients in the current analysis were treated within 24 hours and 24 were treated after 24 hours. Length of stay was significantly shorter in the early-treatment group at 15.6 days vs. 29.4 days in the late-treatment group; however, complications (20 vs. 11) and mortality (1 vs. 2) were similar, Dr. Hubka said.

"Time to diagnosis continues to be important; however, management in an experienced center facile with all current management techniques is the major issue affecting outcomes," he said.

The percentage of cases referred to the tertiary referral center was 50% from 1989 to 1992 and 79% from 2005 to 2009. Referred patients were significantly more likely to be treated more than 24 hours after perforation.

The improvement in outcomes is likely related to increasing diversity of treatment techniques and management in specialty centers, Dr. Hubka said.

Invited discussant Dr. Jeffrey Peters from the University of Rochester (N. Y.) Medical Center said, "What you heard was an increasing chorus of a paradigm change, if you will, that’s sort of paradoxical to most of us – that someone with a hole in their esophagus does better if you don’t operate on them. I still struggle trying not to do that when patients present in the emergency room with these issues."

Still, he described the improvement in outcomes as true progress for patients. Dr. Peters noted that the etiology of acute perforations has changed over time, with most now iatrogenic, and thus the benefit of early treatment may not be as critical as in years past. He said referral to a tertiary center is important, but that the paper did not prove a causal effect.

Based on the findings, Dr. Peters asked when surgeons should operate, how the size of the injury and presence of underlying disease should be taken into account in treatment decisions, and when surgery should be considered if nonoperative therapy fails.

Dr. Hubka said patients with larger esophageal tears or injuries and moderate mediastinal pleural contamination who can tolerate surgery are the ones who proceed to the operating room. He suggested that the study’s operative rate would likely have been higher if patients with perforations due to neoplasia or cancer had been included and that the presence of such underlying disease would surely push them toward operative management in clinical practice. Finally, if a patient becomes unstable or their level of contamination increases despite nonsurgical management, they would proceed to surgery and decontamination.

"A point of our study is that this management, whether it’s endoscopic or operative, should be performed by surgeons because we have all the tools to manage all patients appropriately," Dr. Hubka said.

The study authors and discussant said that they had no financial disclosures.

CHICAGO – Nonsurgical approaches are beginning to dominate the management of acute esophageal perforations.

An analysis of 81 consecutive acute esophageal perforation cases between June 1989 and March 2009 revealed that nonsurgical management jumped from 0% during the first 4 years of the study to 75% in the last 4 years (P value less than .001).

The average length of stay declined significantly over the same period, from 26 days to 20 days (P less than .001), while complications trended downward from 50% vs. 33%, Dr. Michal Hubka reported on behalf of lead author Dr. Madhan Kumar Kuppusamy and their colleagues at Virginia Mason Medical Center in Seattle.

In all, 33 patients were managed nonoperatively and 48 surgically. Primary repair was the most common surgical approach (34 cases). Nonsurgical treatments included endoscopic stenting (11 cases), drainage procedures including mediastinal drainage (13 cases), total parenteral nutrition (7 cases), Dobhoff feeding tube (5 cases), gastrostomy (5 cases), endoscopic repair with clips or glue (3 cases), and feeding jejunostomy (3 cases).

"Nonoperative treatment options are increasing and surgeons must be able to apply these techniques to improve outcomes," Dr. Hubka said at the annual meeting of the Western Surgical Association.

Hybrid-type management was performed in 21% of patients, and most often took the form of endoscopic stents or drainage at the time of open or thorascopic drainage or decortication.

The nonoperative group was less likely than the operative group to experience pneumonia (4 patients vs. 7 patients) and dysrhythmias (4 patients vs. 11 patients), but more likely to experience persistent leak at the 14th day (3 vs. 2), stent migration (3 vs. 0), sepsis (1 vs. 0), and renal failure (1 vs. 0), Dr. Hubka said. Deep vein thrombosis occurred in one patient in each group.

Two patients managed medically died vs. one treated surgically (6% vs. 2%), for an overall mortality rate of 3.7%. A historical comparison of nine other studies involving nonoperative management of esophageal perforations presented by Dr. Hubka showed mortality rates reaching a high of 24% between 1973 and 1993 and a low of 3.8% between 1990 and 2001.

One of those nine studies identified a stepwise increase in mortality as time from perforation to diagnosis increased, with 5% of 75 patients dying with an immediate diagnosis vs. 14% with a diagnosis within 24 hours and 44% if the diagnosis occurred after 24 hours (Eur. J. Cardiothorac. Surg. 2003;23:799-804).

In all, 57 patients in the current analysis were treated within 24 hours and 24 were treated after 24 hours. Length of stay was significantly shorter in the early-treatment group at 15.6 days vs. 29.4 days in the late-treatment group; however, complications (20 vs. 11) and mortality (1 vs. 2) were similar, Dr. Hubka said.

"Time to diagnosis continues to be important; however, management in an experienced center facile with all current management techniques is the major issue affecting outcomes," he said.

The percentage of cases referred to the tertiary referral center was 50% from 1989 to 1992 and 79% from 2005 to 2009. Referred patients were significantly more likely to be treated more than 24 hours after perforation.

The improvement in outcomes is likely related to increasing diversity of treatment techniques and management in specialty centers, Dr. Hubka said.

Invited discussant Dr. Jeffrey Peters from the University of Rochester (N. Y.) Medical Center said, "What you heard was an increasing chorus of a paradigm change, if you will, that’s sort of paradoxical to most of us – that someone with a hole in their esophagus does better if you don’t operate on them. I still struggle trying not to do that when patients present in the emergency room with these issues."

Still, he described the improvement in outcomes as true progress for patients. Dr. Peters noted that the etiology of acute perforations has changed over time, with most now iatrogenic, and thus the benefit of early treatment may not be as critical as in years past. He said referral to a tertiary center is important, but that the paper did not prove a causal effect.

Based on the findings, Dr. Peters asked when surgeons should operate, how the size of the injury and presence of underlying disease should be taken into account in treatment decisions, and when surgery should be considered if nonoperative therapy fails.

Dr. Hubka said patients with larger esophageal tears or injuries and moderate mediastinal pleural contamination who can tolerate surgery are the ones who proceed to the operating room. He suggested that the study’s operative rate would likely have been higher if patients with perforations due to neoplasia or cancer had been included and that the presence of such underlying disease would surely push them toward operative management in clinical practice. Finally, if a patient becomes unstable or their level of contamination increases despite nonsurgical management, they would proceed to surgery and decontamination.

"A point of our study is that this management, whether it’s endoscopic or operative, should be performed by surgeons because we have all the tools to manage all patients appropriately," Dr. Hubka said.

The study authors and discussant said that they had no financial disclosures.

Major Finding: Parous women with 5 years or more of oral contraceptive use had a significant 59% reduced risk of endometriosis, compared with those who never used oral contraceptives.

Data Source: Retrospective cohort study of 9,427 women in the prospective Australian Longitudinal Study on Women's Health.

Disclosures: Dr. Tu disclosed no conflicts of interest.

Chicago — Longer oral contraceptive use plus parity were protective against the development of endometriosis in a retrospective cohort study of young women in the Australian Longitudinal Study on Women's Health.

Researchers analyzed data at four time points over a 10-year-period from a subset of 9,427 women aged 18-23 years at the time of entry in the ALSWH. The study is prospectively following 40,000 women over 20 years to better estimate the association between oral contraceptive (OC) use and risk of endometriosis.

A total of 514 new endometriosis cases occurred over the 10 years, with an incidence rate of 670 per 100,000 person-years of risk, Dr. Frank Tu and his associates reported in a poster at the meeting.

Univariate analysis revealed that immediate prior OC use was a risk factor for endometriosis. In bivariate analysis, however, OC use was a risk factor for endometriosis in nulliparous women but not in parous women.

The researchers then conducted a multivariate Cox regression analysis that adjusted for such confounders as body mass index (BMI), parity, geographical location, OC use for other reasons, urinary pain, marital status, SF-36 (Short-Form–36) pain score, dysmenorrhea, total years of OC use, and its interaction with parity.

In this analysis, nulliparous women with prior exposure to OCs had a dose-dependent increased risk of developing endometriosis; however, prior exposure to OCs was protective among parous women, reported Dr. Tu of the NorthShore University Health System in Chicago.

Compared with nulliparous women who never used OCs, the risk for a subsequent diagnosis of endometriosis was 1.8 times higher in nulliparous women who had used OCs for less than 5 years, and 2.3 times higher in those with at least 5 years of OC use.

In contrast, parous women with 5 years or more of OC exposure had a significant 59% reduced risk of endometriosis, compared with those who never used OCs. The risk of endometriosis was reduced 55% in parous women with less than 5 years of OC, but this did not reach statistical significance.

“While our study revealed that longer [OC] use plus parity were protective against endometriosis, rigorous mechanistic studies are needed to validate if use of exogenous sex hormones is a risk factor for the development of endometriosis and pelvic pain conditions among nulliparous women,” the authors concluded.

At midstudy, endometriosis patients were significantly more likely than controls to report having heavy menstrual periods “sometimes or often” (46% vs. 25%), having constipation (19% vs. 13%), painful urination (17% vs. 8%), severe period pain (64% vs. 38%), low back pain (48% vs. 37%), and depression (4% vs. 2%).

Roughly two-thirds of cases and controls had an acceptable BMI of 18.5-25 kg/m

Nulliparous women with prior exposure to OCs had an increased risk of developing endometriosis.

Source DR. TU

Major Finding: Parous women with 5 years or more of oral contraceptive use had a significant 59% reduced risk of endometriosis, compared with those who never used oral contraceptives.

Data Source: Retrospective cohort study of 9,427 women in the prospective Australian Longitudinal Study on Women's Health.

Disclosures: Dr. Tu disclosed no conflicts of interest.

Chicago — Longer oral contraceptive use plus parity were protective against the development of endometriosis in a retrospective cohort study of young women in the Australian Longitudinal Study on Women's Health.

Researchers analyzed data at four time points over a 10-year-period from a subset of 9,427 women aged 18-23 years at the time of entry in the ALSWH. The study is prospectively following 40,000 women over 20 years to better estimate the association between oral contraceptive (OC) use and risk of endometriosis.

A total of 514 new endometriosis cases occurred over the 10 years, with an incidence rate of 670 per 100,000 person-years of risk, Dr. Frank Tu and his associates reported in a poster at the meeting.

Univariate analysis revealed that immediate prior OC use was a risk factor for endometriosis. In bivariate analysis, however, OC use was a risk factor for endometriosis in nulliparous women but not in parous women.

The researchers then conducted a multivariate Cox regression analysis that adjusted for such confounders as body mass index (BMI), parity, geographical location, OC use for other reasons, urinary pain, marital status, SF-36 (Short-Form–36) pain score, dysmenorrhea, total years of OC use, and its interaction with parity.

In this analysis, nulliparous women with prior exposure to OCs had a dose-dependent increased risk of developing endometriosis; however, prior exposure to OCs was protective among parous women, reported Dr. Tu of the NorthShore University Health System in Chicago.

Compared with nulliparous women who never used OCs, the risk for a subsequent diagnosis of endometriosis was 1.8 times higher in nulliparous women who had used OCs for less than 5 years, and 2.3 times higher in those with at least 5 years of OC use.

In contrast, parous women with 5 years or more of OC exposure had a significant 59% reduced risk of endometriosis, compared with those who never used OCs. The risk of endometriosis was reduced 55% in parous women with less than 5 years of OC, but this did not reach statistical significance.

“While our study revealed that longer [OC] use plus parity were protective against endometriosis, rigorous mechanistic studies are needed to validate if use of exogenous sex hormones is a risk factor for the development of endometriosis and pelvic pain conditions among nulliparous women,” the authors concluded.

At midstudy, endometriosis patients were significantly more likely than controls to report having heavy menstrual periods “sometimes or often” (46% vs. 25%), having constipation (19% vs. 13%), painful urination (17% vs. 8%), severe period pain (64% vs. 38%), low back pain (48% vs. 37%), and depression (4% vs. 2%).

Roughly two-thirds of cases and controls had an acceptable BMI of 18.5-25 kg/m

Nulliparous women with prior exposure to OCs had an increased risk of developing endometriosis.

Source DR. TU

Major Finding: Parous women with 5 years or more of oral contraceptive use had a significant 59% reduced risk of endometriosis, compared with those who never used oral contraceptives.

Data Source: Retrospective cohort study of 9,427 women in the prospective Australian Longitudinal Study on Women's Health.

Disclosures: Dr. Tu disclosed no conflicts of interest.

Chicago — Longer oral contraceptive use plus parity were protective against the development of endometriosis in a retrospective cohort study of young women in the Australian Longitudinal Study on Women's Health.

Researchers analyzed data at four time points over a 10-year-period from a subset of 9,427 women aged 18-23 years at the time of entry in the ALSWH. The study is prospectively following 40,000 women over 20 years to better estimate the association between oral contraceptive (OC) use and risk of endometriosis.

A total of 514 new endometriosis cases occurred over the 10 years, with an incidence rate of 670 per 100,000 person-years of risk, Dr. Frank Tu and his associates reported in a poster at the meeting.

Univariate analysis revealed that immediate prior OC use was a risk factor for endometriosis. In bivariate analysis, however, OC use was a risk factor for endometriosis in nulliparous women but not in parous women.

The researchers then conducted a multivariate Cox regression analysis that adjusted for such confounders as body mass index (BMI), parity, geographical location, OC use for other reasons, urinary pain, marital status, SF-36 (Short-Form–36) pain score, dysmenorrhea, total years of OC use, and its interaction with parity.

In this analysis, nulliparous women with prior exposure to OCs had a dose-dependent increased risk of developing endometriosis; however, prior exposure to OCs was protective among parous women, reported Dr. Tu of the NorthShore University Health System in Chicago.

Compared with nulliparous women who never used OCs, the risk for a subsequent diagnosis of endometriosis was 1.8 times higher in nulliparous women who had used OCs for less than 5 years, and 2.3 times higher in those with at least 5 years of OC use.

In contrast, parous women with 5 years or more of OC exposure had a significant 59% reduced risk of endometriosis, compared with those who never used OCs. The risk of endometriosis was reduced 55% in parous women with less than 5 years of OC, but this did not reach statistical significance.

“While our study revealed that longer [OC] use plus parity were protective against endometriosis, rigorous mechanistic studies are needed to validate if use of exogenous sex hormones is a risk factor for the development of endometriosis and pelvic pain conditions among nulliparous women,” the authors concluded.

At midstudy, endometriosis patients were significantly more likely than controls to report having heavy menstrual periods “sometimes or often” (46% vs. 25%), having constipation (19% vs. 13%), painful urination (17% vs. 8%), severe period pain (64% vs. 38%), low back pain (48% vs. 37%), and depression (4% vs. 2%).

Roughly two-thirds of cases and controls had an acceptable BMI of 18.5-25 kg/m

Nulliparous women with prior exposure to OCs had an increased risk of developing endometriosis.

Source DR. TU

INDIANAPOLIS – A retrospective analysis has shed some light on the prevalence of carotid artery stent fracture but ultimately underscores how little is known about the durability of carotid stents.

No accepted standard currently exists for carotid artery stent surveillance specific to fracture identification. In addition, the etiology of these fractures is unknown, as is their clinical relevance, Dr. Anthony Nigliazzo said at the meeting.

He presented a retrospective analysis of 91 patients who received 107 carotid artery stents from January 2002 through December 2009 at the Michigan Vascular Center in Flint, a group that has significant carotid artery stenting (CAS) experience, including 14 CAS trials.

Two vascular surgeons and two radiologists independently reviewed anteroposterior and lateral cervical x-rays taken at a median follow-up of 28 months to evaluate for stent fractures. Because the reviewers did not all agree, a peer review consensus conference was held to determine whether fractures had occurred, Dr. Nigliazzo said. Information from duplex ultrasounds obtained at 30 days, 6 months, and 1 year was also used to determine flow velocities and to correlate with a fracture diagnosis.

Ultimately, the experts agreed that 4 of the 107 stents (3.7%) were fractured. Only one of the fractures had any evidence of restenosis, and none had clinical sequelae or were symptomatic at the time of identification.

When the team asked outside expert Dr. Michael Dake, a pioneer in endovascular stent development from Stanford (Calif.) University Medical Center, to review the same films, however, the fracture rate reached 7.7% for the 91 patients and 107 stents.

Overall, Dr. Nigliazzo said that the prevalence of carotid artery stent fracture appears to be low, but added that “the true incidence of stent fracture remains elusive.”

Part of the difficulty in making the diagnosis is that some fractures could not be seen on certain x-ray projections, and many stents had deformities. One such deformity – called “fish scaling,” in which layers of an open-cell stent protrude – makes it appear that a fracture is present when it is not. Although vessel angulation greater than 45 degrees and calcification have been identified as risk factors for stent fracture, this was not apparent in the analysis, said Dr. Nigliazzo, a senior resident with the department of surgery at Michigan State University in Flint.

He noted that reported prevalence rates of carotid stent fracture vary widely, from 1.9% to 29%. “We believe this magnifies the difficulty in identifying stent fractures and the different modalities that investigators are using,” he said.

The researchers, led by Dr. Robert G. Molnar, who is with the Michigan Vascular Center and is chief of vascular surgery at McLaren Regional Medical Center, also in Flint, called for further research to determine the ideal methods for long-term CAS surveillance. For the time being, they recommended obtaining anteroposterior/lateral and oblique images for poststent fracture surveillance. One attendee cautioned that this type of surveillance may be “overkill” until it's known whether clinical sequelae are associated with stent fracture.

Dr. Nigliazzo responded that the argument can go both ways, and highlighted a recent prospective Italian study reporting that stent fracture was significantly associated with restenosis (J. Vasc. Surg. 2010;51:1397-405).

Limitations of the current study include its retrospective design and the analysis of only 33% of the 272 patients who received stents during the study.

The cohort had a mean age of 71.6 years and was mostly male (61%). Overall, 45% had received a carotid stent after carotid endarterectomy whereas 15% did so after radiation. Only 4% were classified as low risk by entry criteria for the CREST and CARESS trials.

“Fish scaling” along the lateral border of this carotid artery stent, along with a high degree of angulation, makes fracture identification difficult.

Source Courtesy Mclaren Regional Medical Center

INDIANAPOLIS – A retrospective analysis has shed some light on the prevalence of carotid artery stent fracture but ultimately underscores how little is known about the durability of carotid stents.

No accepted standard currently exists for carotid artery stent surveillance specific to fracture identification. In addition, the etiology of these fractures is unknown, as is their clinical relevance, Dr. Anthony Nigliazzo said at the meeting.

He presented a retrospective analysis of 91 patients who received 107 carotid artery stents from January 2002 through December 2009 at the Michigan Vascular Center in Flint, a group that has significant carotid artery stenting (CAS) experience, including 14 CAS trials.

Two vascular surgeons and two radiologists independently reviewed anteroposterior and lateral cervical x-rays taken at a median follow-up of 28 months to evaluate for stent fractures. Because the reviewers did not all agree, a peer review consensus conference was held to determine whether fractures had occurred, Dr. Nigliazzo said. Information from duplex ultrasounds obtained at 30 days, 6 months, and 1 year was also used to determine flow velocities and to correlate with a fracture diagnosis.

Ultimately, the experts agreed that 4 of the 107 stents (3.7%) were fractured. Only one of the fractures had any evidence of restenosis, and none had clinical sequelae or were symptomatic at the time of identification.

When the team asked outside expert Dr. Michael Dake, a pioneer in endovascular stent development from Stanford (Calif.) University Medical Center, to review the same films, however, the fracture rate reached 7.7% for the 91 patients and 107 stents.

Overall, Dr. Nigliazzo said that the prevalence of carotid artery stent fracture appears to be low, but added that “the true incidence of stent fracture remains elusive.”

Part of the difficulty in making the diagnosis is that some fractures could not be seen on certain x-ray projections, and many stents had deformities. One such deformity – called “fish scaling,” in which layers of an open-cell stent protrude – makes it appear that a fracture is present when it is not. Although vessel angulation greater than 45 degrees and calcification have been identified as risk factors for stent fracture, this was not apparent in the analysis, said Dr. Nigliazzo, a senior resident with the department of surgery at Michigan State University in Flint.

He noted that reported prevalence rates of carotid stent fracture vary widely, from 1.9% to 29%. “We believe this magnifies the difficulty in identifying stent fractures and the different modalities that investigators are using,” he said.

The researchers, led by Dr. Robert G. Molnar, who is with the Michigan Vascular Center and is chief of vascular surgery at McLaren Regional Medical Center, also in Flint, called for further research to determine the ideal methods for long-term CAS surveillance. For the time being, they recommended obtaining anteroposterior/lateral and oblique images for poststent fracture surveillance. One attendee cautioned that this type of surveillance may be “overkill” until it's known whether clinical sequelae are associated with stent fracture.

Dr. Nigliazzo responded that the argument can go both ways, and highlighted a recent prospective Italian study reporting that stent fracture was significantly associated with restenosis (J. Vasc. Surg. 2010;51:1397-405).

Limitations of the current study include its retrospective design and the analysis of only 33% of the 272 patients who received stents during the study.

The cohort had a mean age of 71.6 years and was mostly male (61%). Overall, 45% had received a carotid stent after carotid endarterectomy whereas 15% did so after radiation. Only 4% were classified as low risk by entry criteria for the CREST and CARESS trials.

“Fish scaling” along the lateral border of this carotid artery stent, along with a high degree of angulation, makes fracture identification difficult.

Source Courtesy Mclaren Regional Medical Center

INDIANAPOLIS – A retrospective analysis has shed some light on the prevalence of carotid artery stent fracture but ultimately underscores how little is known about the durability of carotid stents.

No accepted standard currently exists for carotid artery stent surveillance specific to fracture identification. In addition, the etiology of these fractures is unknown, as is their clinical relevance, Dr. Anthony Nigliazzo said at the meeting.

He presented a retrospective analysis of 91 patients who received 107 carotid artery stents from January 2002 through December 2009 at the Michigan Vascular Center in Flint, a group that has significant carotid artery stenting (CAS) experience, including 14 CAS trials.

Two vascular surgeons and two radiologists independently reviewed anteroposterior and lateral cervical x-rays taken at a median follow-up of 28 months to evaluate for stent fractures. Because the reviewers did not all agree, a peer review consensus conference was held to determine whether fractures had occurred, Dr. Nigliazzo said. Information from duplex ultrasounds obtained at 30 days, 6 months, and 1 year was also used to determine flow velocities and to correlate with a fracture diagnosis.

Ultimately, the experts agreed that 4 of the 107 stents (3.7%) were fractured. Only one of the fractures had any evidence of restenosis, and none had clinical sequelae or were symptomatic at the time of identification.

When the team asked outside expert Dr. Michael Dake, a pioneer in endovascular stent development from Stanford (Calif.) University Medical Center, to review the same films, however, the fracture rate reached 7.7% for the 91 patients and 107 stents.

Overall, Dr. Nigliazzo said that the prevalence of carotid artery stent fracture appears to be low, but added that “the true incidence of stent fracture remains elusive.”

Part of the difficulty in making the diagnosis is that some fractures could not be seen on certain x-ray projections, and many stents had deformities. One such deformity – called “fish scaling,” in which layers of an open-cell stent protrude – makes it appear that a fracture is present when it is not. Although vessel angulation greater than 45 degrees and calcification have been identified as risk factors for stent fracture, this was not apparent in the analysis, said Dr. Nigliazzo, a senior resident with the department of surgery at Michigan State University in Flint.

He noted that reported prevalence rates of carotid stent fracture vary widely, from 1.9% to 29%. “We believe this magnifies the difficulty in identifying stent fractures and the different modalities that investigators are using,” he said.

The researchers, led by Dr. Robert G. Molnar, who is with the Michigan Vascular Center and is chief of vascular surgery at McLaren Regional Medical Center, also in Flint, called for further research to determine the ideal methods for long-term CAS surveillance. For the time being, they recommended obtaining anteroposterior/lateral and oblique images for poststent fracture surveillance. One attendee cautioned that this type of surveillance may be “overkill” until it's known whether clinical sequelae are associated with stent fracture.

Dr. Nigliazzo responded that the argument can go both ways, and highlighted a recent prospective Italian study reporting that stent fracture was significantly associated with restenosis (J. Vasc. Surg. 2010;51:1397-405).

Limitations of the current study include its retrospective design and the analysis of only 33% of the 272 patients who received stents during the study.

The cohort had a mean age of 71.6 years and was mostly male (61%). Overall, 45% had received a carotid stent after carotid endarterectomy whereas 15% did so after radiation. Only 4% were classified as low risk by entry criteria for the CREST and CARESS trials.

“Fish scaling” along the lateral border of this carotid artery stent, along with a high degree of angulation, makes fracture identification difficult.

Source Courtesy Mclaren Regional Medical Center

Major Finding: Addition of CRT to an ICD significantly reduced the rate of death and heart failure hospitalization by 25% in patients with NYHA class II or III heart failure.

Data Source: Randomized trial in 1,798 patients with mild to moderate heart failure.

Disclosures: RAFT was funded by the Canadian Institutes of Health Research and Medtronic of Canada. Dr. Tang disclosed research support from Medtronic, St. Jude Medical, and Boston Scientific. Dr. Yancy said he had no financial conflicts of interest.

CHICAGO – for the first time, cardiac resynchronization therapy has been shown to offer a survival benefit beyond that provided by an implantable cardioverter defibrillator in patients with mild heart failure, a study has shown.

The addition of cardiac resynchronization therapy (CRT) to an implantable cardioverter defibrillator (ICD) and optimal medical therapy significantly reduced the rates of death and heart failure hospitalization from 40% with an ICD alone to 33% in the multicenter Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT).

The relative risk of death was reduced by 25% among patients who received CRT plus ICD, resulting in an absolute mortality reduction of 6% at 5 years, Dr. Anthony Tang reported at the meeting. Fourteen patients would need to be treated with CRT plus ICD for 5 years to prevent one death.

Significantly fewer CRT-ICD patients were hospitalized for heart failure (19.5%, or 174/894) than ICD-only patients (26%, or 236/904). This meant that 11 patients would need to be treated with CRT plus ICD for 5 years to prevent one heart failure hospitalization, said Dr. Tang, professor of medicine at the University of British Columbia, Vancouver.

RAFT enrolled 1,798 patients (mean age, 66 years), who had New York Heart Association class II or III heart failure, a left ventricular ejection fraction (LVEF) of 30% or less, and a wide QRS duration of at least 120 milliseconds or a paced QRS duration of at least 200 milliseconds.

CRT with or without an ICD is currently indicated only for the treatment of patients with NYHA functional class III or ambulatory class IV heart failure.

The data are likely to change clinical practice, said invited discussant Dr. Clyde W. Yancy, medical director of Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallas and immediate past president of the AHA.

He observed that a suite of randomized trials, including COMPANION, CARE-HF, MADIT-CRT, REVERSE, and now RAFT demonstrate compellingly that CRT is effective in heart failure.

“The benefit can now be extended to patients that have mild heart failure,” he said.

In the pivotal Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT), however, the use of CRT-ICD therapy decreased the risk of heart failure events but not the risk of death among NYHA class I or II patients with an ejection fraction of 30% or less and a QRS duration of 130 milliseconds or more (N. Engl. J. Med. 2009;361:1329-38).

Dr. Yancy observed that CRT plus ICD is used in only about one-third of heart failure patients and suggested that its limited uptake is due to persistent equipoise, postprocedural risks that are not insignificant, an early failure rate of about 5% and a late failure rate of up to 25%, imprecise markers of clinical response, and current guidelines.

The improved outcomes, however, did come at the cost of increased adverse events. Within 30 days of device implantation, significantly more CRT-ICD patients than ICD-alone patients had lead dislodgment (61 vs. 20 patients) and coronary sinus dissection (11 vs. 0), Dr. Tang reported. The CRT-ICD and ICD-alone groups had similar rates of hemothorax or pneumothorax (11 vs. 8 patients), pocket hematoma (14 vs. 11), pocket infection (21 vs. 16), tamponade (1 vs. 2), and device pocket revision (4 vs. 1).

An analysis by NYHA class showed that the majority of positive results held true, Dr. Tang said. The primary composite end point was significantly improved in both NYHA class II and III patients, while death from any cause was significantly improved among class II, but not class III patients.

The RAFT data were simultaneously published online by the New England Journal of Medicine (2010;10.1056/NEJM0a1009540).

Major Finding: Addition of CRT to an ICD significantly reduced the rate of death and heart failure hospitalization by 25% in patients with NYHA class II or III heart failure.

Data Source: Randomized trial in 1,798 patients with mild to moderate heart failure.

Disclosures: RAFT was funded by the Canadian Institutes of Health Research and Medtronic of Canada. Dr. Tang disclosed research support from Medtronic, St. Jude Medical, and Boston Scientific. Dr. Yancy said he had no financial conflicts of interest.

CHICAGO – for the first time, cardiac resynchronization therapy has been shown to offer a survival benefit beyond that provided by an implantable cardioverter defibrillator in patients with mild heart failure, a study has shown.

The addition of cardiac resynchronization therapy (CRT) to an implantable cardioverter defibrillator (ICD) and optimal medical therapy significantly reduced the rates of death and heart failure hospitalization from 40% with an ICD alone to 33% in the multicenter Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT).

The relative risk of death was reduced by 25% among patients who received CRT plus ICD, resulting in an absolute mortality reduction of 6% at 5 years, Dr. Anthony Tang reported at the meeting. Fourteen patients would need to be treated with CRT plus ICD for 5 years to prevent one death.

Significantly fewer CRT-ICD patients were hospitalized for heart failure (19.5%, or 174/894) than ICD-only patients (26%, or 236/904). This meant that 11 patients would need to be treated with CRT plus ICD for 5 years to prevent one heart failure hospitalization, said Dr. Tang, professor of medicine at the University of British Columbia, Vancouver.

RAFT enrolled 1,798 patients (mean age, 66 years), who had New York Heart Association class II or III heart failure, a left ventricular ejection fraction (LVEF) of 30% or less, and a wide QRS duration of at least 120 milliseconds or a paced QRS duration of at least 200 milliseconds.

CRT with or without an ICD is currently indicated only for the treatment of patients with NYHA functional class III or ambulatory class IV heart failure.

The data are likely to change clinical practice, said invited discussant Dr. Clyde W. Yancy, medical director of Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallas and immediate past president of the AHA.

He observed that a suite of randomized trials, including COMPANION, CARE-HF, MADIT-CRT, REVERSE, and now RAFT demonstrate compellingly that CRT is effective in heart failure.

“The benefit can now be extended to patients that have mild heart failure,” he said.

In the pivotal Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT), however, the use of CRT-ICD therapy decreased the risk of heart failure events but not the risk of death among NYHA class I or II patients with an ejection fraction of 30% or less and a QRS duration of 130 milliseconds or more (N. Engl. J. Med. 2009;361:1329-38).

Dr. Yancy observed that CRT plus ICD is used in only about one-third of heart failure patients and suggested that its limited uptake is due to persistent equipoise, postprocedural risks that are not insignificant, an early failure rate of about 5% and a late failure rate of up to 25%, imprecise markers of clinical response, and current guidelines.

The improved outcomes, however, did come at the cost of increased adverse events. Within 30 days of device implantation, significantly more CRT-ICD patients than ICD-alone patients had lead dislodgment (61 vs. 20 patients) and coronary sinus dissection (11 vs. 0), Dr. Tang reported. The CRT-ICD and ICD-alone groups had similar rates of hemothorax or pneumothorax (11 vs. 8 patients), pocket hematoma (14 vs. 11), pocket infection (21 vs. 16), tamponade (1 vs. 2), and device pocket revision (4 vs. 1).

An analysis by NYHA class showed that the majority of positive results held true, Dr. Tang said. The primary composite end point was significantly improved in both NYHA class II and III patients, while death from any cause was significantly improved among class II, but not class III patients.

The RAFT data were simultaneously published online by the New England Journal of Medicine (2010;10.1056/NEJM0a1009540).

Major Finding: Addition of CRT to an ICD significantly reduced the rate of death and heart failure hospitalization by 25% in patients with NYHA class II or III heart failure.

Data Source: Randomized trial in 1,798 patients with mild to moderate heart failure.

Disclosures: RAFT was funded by the Canadian Institutes of Health Research and Medtronic of Canada. Dr. Tang disclosed research support from Medtronic, St. Jude Medical, and Boston Scientific. Dr. Yancy said he had no financial conflicts of interest.

CHICAGO – for the first time, cardiac resynchronization therapy has been shown to offer a survival benefit beyond that provided by an implantable cardioverter defibrillator in patients with mild heart failure, a study has shown.

The addition of cardiac resynchronization therapy (CRT) to an implantable cardioverter defibrillator (ICD) and optimal medical therapy significantly reduced the rates of death and heart failure hospitalization from 40% with an ICD alone to 33% in the multicenter Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT).

The relative risk of death was reduced by 25% among patients who received CRT plus ICD, resulting in an absolute mortality reduction of 6% at 5 years, Dr. Anthony Tang reported at the meeting. Fourteen patients would need to be treated with CRT plus ICD for 5 years to prevent one death.

Significantly fewer CRT-ICD patients were hospitalized for heart failure (19.5%, or 174/894) than ICD-only patients (26%, or 236/904). This meant that 11 patients would need to be treated with CRT plus ICD for 5 years to prevent one heart failure hospitalization, said Dr. Tang, professor of medicine at the University of British Columbia, Vancouver.

RAFT enrolled 1,798 patients (mean age, 66 years), who had New York Heart Association class II or III heart failure, a left ventricular ejection fraction (LVEF) of 30% or less, and a wide QRS duration of at least 120 milliseconds or a paced QRS duration of at least 200 milliseconds.

CRT with or without an ICD is currently indicated only for the treatment of patients with NYHA functional class III or ambulatory class IV heart failure.

The data are likely to change clinical practice, said invited discussant Dr. Clyde W. Yancy, medical director of Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallas and immediate past president of the AHA.

He observed that a suite of randomized trials, including COMPANION, CARE-HF, MADIT-CRT, REVERSE, and now RAFT demonstrate compellingly that CRT is effective in heart failure.

“The benefit can now be extended to patients that have mild heart failure,” he said.

In the pivotal Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT), however, the use of CRT-ICD therapy decreased the risk of heart failure events but not the risk of death among NYHA class I or II patients with an ejection fraction of 30% or less and a QRS duration of 130 milliseconds or more (N. Engl. J. Med. 2009;361:1329-38).

Dr. Yancy observed that CRT plus ICD is used in only about one-third of heart failure patients and suggested that its limited uptake is due to persistent equipoise, postprocedural risks that are not insignificant, an early failure rate of about 5% and a late failure rate of up to 25%, imprecise markers of clinical response, and current guidelines.

The improved outcomes, however, did come at the cost of increased adverse events. Within 30 days of device implantation, significantly more CRT-ICD patients than ICD-alone patients had lead dislodgment (61 vs. 20 patients) and coronary sinus dissection (11 vs. 0), Dr. Tang reported. The CRT-ICD and ICD-alone groups had similar rates of hemothorax or pneumothorax (11 vs. 8 patients), pocket hematoma (14 vs. 11), pocket infection (21 vs. 16), tamponade (1 vs. 2), and device pocket revision (4 vs. 1).

An analysis by NYHA class showed that the majority of positive results held true, Dr. Tang said. The primary composite end point was significantly improved in both NYHA class II and III patients, while death from any cause was significantly improved among class II, but not class III patients.

The RAFT data were simultaneously published online by the New England Journal of Medicine (2010;10.1056/NEJM0a1009540).

CHICAGO — The experimental oral agent anacetrapib increased HDL cholesterol levels by a staggering 138%, compared with placebo, in high-risk patients and did so without the negative side effects that plagued another drug in the same class.

When compared with placebo at 24 weeks, once-daily anacetrapib increased HDL levels from 40 mg/dL to 101 mg/dL and decreased LDL levels by 40% from 81 mg/dL to 45 mg/dL in the double-blind phase III Determining the Efficacy and Tolerability of CETP Inhibition With Anacetrapib (DEFINE) trial.

“This is a total change in what lipids can be,” said senior investigator Dr. Christopher Cannon, who went one step further in a statement describing anacetrapib as having a “knock-your-socks-off effect on HDL and a jaw-dropping effect on LDL” among 1,623 patients already taking a cholesterol-lowering statin and had LDL levels consistent with recommended guidelines.

Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor designed to fight hypercholesterolemia by raising levels of HDL. The strategy was called into question, however, after the experimental CETP inhibitor torcetrapib was found to have off-target effects in the adrenal glands, leading to increased blood pressure, mortality, and cardiovascular events.

Anacetrapib had an acceptable side-effect profile, with no effects on blood pressure electrolytes or aldosterone through 76 weeks of follow-up, Dr. Cannon, with Brigham and Women's Hospital, Boston, reported at a press briefing at the meeting. The prespecified, adjudicated composite end point of death from cardiovascular causes, MI, hospitalization for unstable angina, or stroke occurred in 16 anacetrapib-treated patients and in 21 placebo-treated patients.

Although the trial was not designed as an outcome study, a Bayesian analysis indicated a 94% predictive probability that anacetrapib would not increase cardiovascular events by 25% as seen with torcetrapib.

In addition, anacetrapib reduced the need for revascularization by two-thirds, compared with placebo (8 patients vs. 28 patients), a finding that Dr. Cannon said convinced him that the strategy of CETP inhibition works.

The REVEAL follow-up trial of anacetrapib vs. placebo is being launched in Europe, North America, and Asia in 30,000 patients with occlusive arterial disease, with a primary end point of coronary death, MI, or coronary revascularization, Dr. Cannon announced during the press conference.

Reporters questioned whether increasing HDL really matters, to which Dr. Jessup remarked that HDL is a potent marker of risk and that older data showed that niacin, which also works by increasing HDL, decreased the need for revascularization. Two trials of niacin are also underway that may provide more contemporary data.

There is some concern that the drug might be too powerful and potentially push levels too low, as 18% of patients had to discontinue treatment after their LDL cholesterol level fell below 25 mg/dL.

Follow-up from REVEAL is planned in 4 years, which means that barring any new safety signals, anacetrapib would be submitted for approval in about 2015, Dr. Cannon said in an interview.

Results of DEFINE were published online simultaneously with Dr. Cannon's presentation (N. Engl. J. Med. 2010 [doi:10.1056/NEJMoa1009744]).

CHICAGO — The experimental oral agent anacetrapib increased HDL cholesterol levels by a staggering 138%, compared with placebo, in high-risk patients and did so without the negative side effects that plagued another drug in the same class.

When compared with placebo at 24 weeks, once-daily anacetrapib increased HDL levels from 40 mg/dL to 101 mg/dL and decreased LDL levels by 40% from 81 mg/dL to 45 mg/dL in the double-blind phase III Determining the Efficacy and Tolerability of CETP Inhibition With Anacetrapib (DEFINE) trial.

“This is a total change in what lipids can be,” said senior investigator Dr. Christopher Cannon, who went one step further in a statement describing anacetrapib as having a “knock-your-socks-off effect on HDL and a jaw-dropping effect on LDL” among 1,623 patients already taking a cholesterol-lowering statin and had LDL levels consistent with recommended guidelines.

Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor designed to fight hypercholesterolemia by raising levels of HDL. The strategy was called into question, however, after the experimental CETP inhibitor torcetrapib was found to have off-target effects in the adrenal glands, leading to increased blood pressure, mortality, and cardiovascular events.

Anacetrapib had an acceptable side-effect profile, with no effects on blood pressure electrolytes or aldosterone through 76 weeks of follow-up, Dr. Cannon, with Brigham and Women's Hospital, Boston, reported at a press briefing at the meeting. The prespecified, adjudicated composite end point of death from cardiovascular causes, MI, hospitalization for unstable angina, or stroke occurred in 16 anacetrapib-treated patients and in 21 placebo-treated patients.

Although the trial was not designed as an outcome study, a Bayesian analysis indicated a 94% predictive probability that anacetrapib would not increase cardiovascular events by 25% as seen with torcetrapib.

In addition, anacetrapib reduced the need for revascularization by two-thirds, compared with placebo (8 patients vs. 28 patients), a finding that Dr. Cannon said convinced him that the strategy of CETP inhibition works.

The REVEAL follow-up trial of anacetrapib vs. placebo is being launched in Europe, North America, and Asia in 30,000 patients with occlusive arterial disease, with a primary end point of coronary death, MI, or coronary revascularization, Dr. Cannon announced during the press conference.

Reporters questioned whether increasing HDL really matters, to which Dr. Jessup remarked that HDL is a potent marker of risk and that older data showed that niacin, which also works by increasing HDL, decreased the need for revascularization. Two trials of niacin are also underway that may provide more contemporary data.

There is some concern that the drug might be too powerful and potentially push levels too low, as 18% of patients had to discontinue treatment after their LDL cholesterol level fell below 25 mg/dL.

Follow-up from REVEAL is planned in 4 years, which means that barring any new safety signals, anacetrapib would be submitted for approval in about 2015, Dr. Cannon said in an interview.

Results of DEFINE were published online simultaneously with Dr. Cannon's presentation (N. Engl. J. Med. 2010 [doi:10.1056/NEJMoa1009744]).

CHICAGO — The experimental oral agent anacetrapib increased HDL cholesterol levels by a staggering 138%, compared with placebo, in high-risk patients and did so without the negative side effects that plagued another drug in the same class.

When compared with placebo at 24 weeks, once-daily anacetrapib increased HDL levels from 40 mg/dL to 101 mg/dL and decreased LDL levels by 40% from 81 mg/dL to 45 mg/dL in the double-blind phase III Determining the Efficacy and Tolerability of CETP Inhibition With Anacetrapib (DEFINE) trial.

“This is a total change in what lipids can be,” said senior investigator Dr. Christopher Cannon, who went one step further in a statement describing anacetrapib as having a “knock-your-socks-off effect on HDL and a jaw-dropping effect on LDL” among 1,623 patients already taking a cholesterol-lowering statin and had LDL levels consistent with recommended guidelines.

Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor designed to fight hypercholesterolemia by raising levels of HDL. The strategy was called into question, however, after the experimental CETP inhibitor torcetrapib was found to have off-target effects in the adrenal glands, leading to increased blood pressure, mortality, and cardiovascular events.

Anacetrapib had an acceptable side-effect profile, with no effects on blood pressure electrolytes or aldosterone through 76 weeks of follow-up, Dr. Cannon, with Brigham and Women's Hospital, Boston, reported at a press briefing at the meeting. The prespecified, adjudicated composite end point of death from cardiovascular causes, MI, hospitalization for unstable angina, or stroke occurred in 16 anacetrapib-treated patients and in 21 placebo-treated patients.

Although the trial was not designed as an outcome study, a Bayesian analysis indicated a 94% predictive probability that anacetrapib would not increase cardiovascular events by 25% as seen with torcetrapib.

In addition, anacetrapib reduced the need for revascularization by two-thirds, compared with placebo (8 patients vs. 28 patients), a finding that Dr. Cannon said convinced him that the strategy of CETP inhibition works.

The REVEAL follow-up trial of anacetrapib vs. placebo is being launched in Europe, North America, and Asia in 30,000 patients with occlusive arterial disease, with a primary end point of coronary death, MI, or coronary revascularization, Dr. Cannon announced during the press conference.

Reporters questioned whether increasing HDL really matters, to which Dr. Jessup remarked that HDL is a potent marker of risk and that older data showed that niacin, which also works by increasing HDL, decreased the need for revascularization. Two trials of niacin are also underway that may provide more contemporary data.

There is some concern that the drug might be too powerful and potentially push levels too low, as 18% of patients had to discontinue treatment after their LDL cholesterol level fell below 25 mg/dL.

Follow-up from REVEAL is planned in 4 years, which means that barring any new safety signals, anacetrapib would be submitted for approval in about 2015, Dr. Cannon said in an interview.

Results of DEFINE were published online simultaneously with Dr. Cannon's presentation (N. Engl. J. Med. 2010 [doi:10.1056/NEJMoa1009744]).

CHICAGO — for the first time, cardiac resynchronization therapy has been shown to offer a survival benefit beyond that provided by an implantable cardioverter defibrillator in patients with mild heart failure, a study has shown.

The addition of cardiac resynchronization therapy (CRT) to an implantable cardioverter defibrillator (ICD) and optimal medical therapy significantly reduced the rates of death and heart failure hospitalization from 40% with an ICD alone to 33% in the multicenter Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT).

The relative risk of death was reduced by 25% among patients who received CRT plus ICD, resulting in an absolute mortality reduction of 6% at 5 years, Dr. Anthony Tang reported at the meeting. Fourteen patients would need to be treated with CRT plus ICD for 5 years to prevent one death.

Significantly fewer CRT-ICD patients were hospitalized for heart failure (19.5%, or 174/894) than ICD-only patients (26%, or 236/904). This meant that 11 patients would need to be treated with CRT plus ICD for 5 years to prevent one heart failure hospitalization, said Dr. Tang, professor of medicine at the University of British Columbia, Vancouver.

RAFT enrolled 1,798 patients (mean age, 66 years), who had New York Heart Association class II or III heart failure, a left ventricular ejection fraction (LVEF) of 30% or less, and a wide QRS duration of at least 120 milliseconds or a paced QRS duration of at least 200 milliseconds. Of note, 80% of patients were NYHA class II because during the trial the protocol was changed to include only class II patients.

CRT with or without an ICD is currently indicated only for the treatment of patients with NYHA functional class III or ambulatory class IV heart failure.

The data are likely to change clinical practice, said invited discussant Dr. Clyde W. Yancy, medical director of Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallasand immediate past president of the AHA.

He observed that a suite of randomized trials including COMPANION, CARE-HF, MADIT-CRT, REVERSE, and now RAFT demonstrate compellingly that CRT is effective in heart failure.

“The benefit can now be extended to patients who have mild heart failure,” he said.

In the pivotal Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT), however, the use of CRT-ICD therapy decreased the risk of heart failure events, but not the risk of death among NYHA class I or II patients with an ejection fraction of 30% or less and a QRS duration of 130 milliseconds or more (N. Engl. J. Med. 2009; 361:1329-38).

Dr. Yancy observed that CRT plus ICD is used in only about one-third of heart failure patients and suggested that its limited uptake is due to persistent equipoise, postprocedural risks that are not insignificant, an early failure rate of about 5% and a late failure rate of up to 25%, imprecise markers of clinical response, and current guidelines. “We should no longer let equipoise enter into our thought process about the benefits of ICD-CRT in heart failure,” he said.

The improved outcomes, however, did come at the cost of increased adverse events. Within 30 days of device implantation, significantly more CRT-ICD patients than ICD-alone patients had lead dislodgment (61 vs. 20 patients) and coronary sinus dissection (11 vs. 0), Dr. Tang reported. The CRT-ICD and ICD-alone groups had similar rates of hemothorax or pneumothorax (11 vs. 8 patients), pocket hematoma (14 vs. 11), pocket infection (21 vs. 16), tamponade (1 vs. 2), and device pocket revision (4 vs. 1).

An analysis by NYHA class showed that the majority of positive results held true, Dr. Tang said. The primary composite end point was significantly improved in both NYHA class II and III patients, while death from any cause was significantly improved among class II, but not class III patients.

Also, a post-hoc subgroup analysis of the primary end point suggests that patients with an intrinsic QRS duration of more than 150 milliseconds derive more benefit from CRT-ICD therapy, as do those with left bundle branch block, although the latter finding was weaker, Dr. Tang said.

RAFT was funded by the Canadian Institutes of Health Research and Medtronic of Canada. Dr. Tang disclosed research support from Boston Scientific, Medtronic, and St. Jude Medical. Dr. Yancy reported having no financial conflicts of interest.

CHICAGO — for the first time, cardiac resynchronization therapy has been shown to offer a survival benefit beyond that provided by an implantable cardioverter defibrillator in patients with mild heart failure, a study has shown.

The addition of cardiac resynchronization therapy (CRT) to an implantable cardioverter defibrillator (ICD) and optimal medical therapy significantly reduced the rates of death and heart failure hospitalization from 40% with an ICD alone to 33% in the multicenter Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT).

The relative risk of death was reduced by 25% among patients who received CRT plus ICD, resulting in an absolute mortality reduction of 6% at 5 years, Dr. Anthony Tang reported at the meeting. Fourteen patients would need to be treated with CRT plus ICD for 5 years to prevent one death.

Significantly fewer CRT-ICD patients were hospitalized for heart failure (19.5%, or 174/894) than ICD-only patients (26%, or 236/904). This meant that 11 patients would need to be treated with CRT plus ICD for 5 years to prevent one heart failure hospitalization, said Dr. Tang, professor of medicine at the University of British Columbia, Vancouver.

RAFT enrolled 1,798 patients (mean age, 66 years), who had New York Heart Association class II or III heart failure, a left ventricular ejection fraction (LVEF) of 30% or less, and a wide QRS duration of at least 120 milliseconds or a paced QRS duration of at least 200 milliseconds. Of note, 80% of patients were NYHA class II because during the trial the protocol was changed to include only class II patients.

CRT with or without an ICD is currently indicated only for the treatment of patients with NYHA functional class III or ambulatory class IV heart failure.

The data are likely to change clinical practice, said invited discussant Dr. Clyde W. Yancy, medical director of Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallasand immediate past president of the AHA.

He observed that a suite of randomized trials including COMPANION, CARE-HF, MADIT-CRT, REVERSE, and now RAFT demonstrate compellingly that CRT is effective in heart failure.

“The benefit can now be extended to patients who have mild heart failure,” he said.

In the pivotal Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT), however, the use of CRT-ICD therapy decreased the risk of heart failure events, but not the risk of death among NYHA class I or II patients with an ejection fraction of 30% or less and a QRS duration of 130 milliseconds or more (N. Engl. J. Med. 2009; 361:1329-38).

Dr. Yancy observed that CRT plus ICD is used in only about one-third of heart failure patients and suggested that its limited uptake is due to persistent equipoise, postprocedural risks that are not insignificant, an early failure rate of about 5% and a late failure rate of up to 25%, imprecise markers of clinical response, and current guidelines. “We should no longer let equipoise enter into our thought process about the benefits of ICD-CRT in heart failure,” he said.

The improved outcomes, however, did come at the cost of increased adverse events. Within 30 days of device implantation, significantly more CRT-ICD patients than ICD-alone patients had lead dislodgment (61 vs. 20 patients) and coronary sinus dissection (11 vs. 0), Dr. Tang reported. The CRT-ICD and ICD-alone groups had similar rates of hemothorax or pneumothorax (11 vs. 8 patients), pocket hematoma (14 vs. 11), pocket infection (21 vs. 16), tamponade (1 vs. 2), and device pocket revision (4 vs. 1).

An analysis by NYHA class showed that the majority of positive results held true, Dr. Tang said. The primary composite end point was significantly improved in both NYHA class II and III patients, while death from any cause was significantly improved among class II, but not class III patients.

Also, a post-hoc subgroup analysis of the primary end point suggests that patients with an intrinsic QRS duration of more than 150 milliseconds derive more benefit from CRT-ICD therapy, as do those with left bundle branch block, although the latter finding was weaker, Dr. Tang said.

RAFT was funded by the Canadian Institutes of Health Research and Medtronic of Canada. Dr. Tang disclosed research support from Boston Scientific, Medtronic, and St. Jude Medical. Dr. Yancy reported having no financial conflicts of interest.

CHICAGO — for the first time, cardiac resynchronization therapy has been shown to offer a survival benefit beyond that provided by an implantable cardioverter defibrillator in patients with mild heart failure, a study has shown.

The addition of cardiac resynchronization therapy (CRT) to an implantable cardioverter defibrillator (ICD) and optimal medical therapy significantly reduced the rates of death and heart failure hospitalization from 40% with an ICD alone to 33% in the multicenter Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT).

The relative risk of death was reduced by 25% among patients who received CRT plus ICD, resulting in an absolute mortality reduction of 6% at 5 years, Dr. Anthony Tang reported at the meeting. Fourteen patients would need to be treated with CRT plus ICD for 5 years to prevent one death.

Significantly fewer CRT-ICD patients were hospitalized for heart failure (19.5%, or 174/894) than ICD-only patients (26%, or 236/904). This meant that 11 patients would need to be treated with CRT plus ICD for 5 years to prevent one heart failure hospitalization, said Dr. Tang, professor of medicine at the University of British Columbia, Vancouver.

RAFT enrolled 1,798 patients (mean age, 66 years), who had New York Heart Association class II or III heart failure, a left ventricular ejection fraction (LVEF) of 30% or less, and a wide QRS duration of at least 120 milliseconds or a paced QRS duration of at least 200 milliseconds. Of note, 80% of patients were NYHA class II because during the trial the protocol was changed to include only class II patients.

CRT with or without an ICD is currently indicated only for the treatment of patients with NYHA functional class III or ambulatory class IV heart failure.

The data are likely to change clinical practice, said invited discussant Dr. Clyde W. Yancy, medical director of Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallasand immediate past president of the AHA.

He observed that a suite of randomized trials including COMPANION, CARE-HF, MADIT-CRT, REVERSE, and now RAFT demonstrate compellingly that CRT is effective in heart failure.

“The benefit can now be extended to patients who have mild heart failure,” he said.

In the pivotal Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT), however, the use of CRT-ICD therapy decreased the risk of heart failure events, but not the risk of death among NYHA class I or II patients with an ejection fraction of 30% or less and a QRS duration of 130 milliseconds or more (N. Engl. J. Med. 2009; 361:1329-38).

Dr. Yancy observed that CRT plus ICD is used in only about one-third of heart failure patients and suggested that its limited uptake is due to persistent equipoise, postprocedural risks that are not insignificant, an early failure rate of about 5% and a late failure rate of up to 25%, imprecise markers of clinical response, and current guidelines. “We should no longer let equipoise enter into our thought process about the benefits of ICD-CRT in heart failure,” he said.

The improved outcomes, however, did come at the cost of increased adverse events. Within 30 days of device implantation, significantly more CRT-ICD patients than ICD-alone patients had lead dislodgment (61 vs. 20 patients) and coronary sinus dissection (11 vs. 0), Dr. Tang reported. The CRT-ICD and ICD-alone groups had similar rates of hemothorax or pneumothorax (11 vs. 8 patients), pocket hematoma (14 vs. 11), pocket infection (21 vs. 16), tamponade (1 vs. 2), and device pocket revision (4 vs. 1).

An analysis by NYHA class showed that the majority of positive results held true, Dr. Tang said. The primary composite end point was significantly improved in both NYHA class II and III patients, while death from any cause was significantly improved among class II, but not class III patients.

Also, a post-hoc subgroup analysis of the primary end point suggests that patients with an intrinsic QRS duration of more than 150 milliseconds derive more benefit from CRT-ICD therapy, as do those with left bundle branch block, although the latter finding was weaker, Dr. Tang said.

RAFT was funded by the Canadian Institutes of Health Research and Medtronic of Canada. Dr. Tang disclosed research support from Boston Scientific, Medtronic, and St. Jude Medical. Dr. Yancy reported having no financial conflicts of interest.

A large randomized national trial has provided the first evidence of a significant reduction in lung cancer deaths with a screening test.

The National Lung Screening Trial (NLST) reported a 20.3% reduction in lung cancer mortality among heavy smokers screened with low-dose helical computed tomography (CT), as compared with those given standard chest x-rays. The trial enrolled more than 53,000 older, high-risk individuals.

In addition, deaths from any cause, including lung cancer, were 7% lower among participants screened with low-dose helical CT, also known as spiral CT.

The initial results were released today by the study sponsor, the National Cancer Institute, after the study's independent data and safety monitoring board recommended halting the trial.

“The fact that low-dose helical CT provides a decided benefit is a result that will have implications for screening and management of lung cancer for many years to come,” Dr. Christine Berg, project officer for the lung screening study at the NCI, said in a statement.

Beginning in 2002, the NLST recruited about 53,500 American men and women, aged 55-74 years, who were current or former smokers with a smoking history of at least 30 pack-years. It randomly assigned them to receive three annual screens with low-dose helical CT or chest x-ray. Helical CT uses x-rays to obtain a multiple-image scan of the entire chest during a 7- to 15-second breath-hold, whereas a standard chest x-ray produces only a single image of the chest from a sub-second breath-hold.

At the time of the Oct. 20, 2010 analysis, 354 deaths from lung cancer had occurred in the CT arm vs. 442 in the chest x-ray group. Approximately 25% of deaths in the NLST were due to lung cancer.

NCI director Harold E. Varmus said the well-designed study used rigorous scientific methods and that its findings could spare countless lives.

“Lung cancer is the leading cause of cancer mortality in the U.S. and throughout the world, so a validated approach that can reduce lung cancer mortality by even 20% has the potential to spare very significant numbers of people from the ravages of this disease,” he said. “But these findings should in no way distract us from continued effort to curtail the use of tobacco, which will remain the major causative factor for lung cancer and several other diseases.”

Like other screening strategies, the use of low-dose helical CT has disadvantages including the cumulative effects of radiation from multiple CT scans, complications among patients who need additional testing to make a definitive lung cancer diagnosis, and the anxiety and added cost associated with investigating incidental findings picked up on CT.

[Editor's note: In 2009, investigators reported that low-dose CT screening was associated with twice the rate of false positives and more unneeded interventions, compared with chest x-ray, in a randomized feasibility trial that preceded the NLST. But low-dose CT also detected twice as many lung cancers as did chest x-ray screens in that study.]

Although the NLST trial cohort was ethnically representative of the high-risk U.S. population, the researchers noted that participants were highly motivated and screened at major medical centers. Thus, the results may not accurately predict the effect of CT screening for other populations.

“What has happened here is that the technology shows you can cut down on lung cancer deaths, the leading cause of cancer mortality, and save nearly as many lives as the number of people who die from breast cancer per year. We as a medical community now need to figure out how to do this in a way that the cost is acceptable to the public,” Dr. Bruce E. Johnson, an official with the American Society of Clinical Oncology and director of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute in Boston, said in a statement.

A more detailed analysis of the NLST results is expected to be published in the coming months, although a paper describing its design and protocol was published by the journal Radiology.

The National Cancer Institute sponsored the study.

A large randomized national trial has provided the first evidence of a significant reduction in lung cancer deaths with a screening test.

The National Lung Screening Trial (NLST) reported a 20.3% reduction in lung cancer mortality among heavy smokers screened with low-dose helical computed tomography (CT), as compared with those given standard chest x-rays. The trial enrolled more than 53,000 older, high-risk individuals.

In addition, deaths from any cause, including lung cancer, were 7% lower among participants screened with low-dose helical CT, also known as spiral CT.

The initial results were released today by the study sponsor, the National Cancer Institute, after the study's independent data and safety monitoring board recommended halting the trial.

“The fact that low-dose helical CT provides a decided benefit is a result that will have implications for screening and management of lung cancer for many years to come,” Dr. Christine Berg, project officer for the lung screening study at the NCI, said in a statement.

Beginning in 2002, the NLST recruited about 53,500 American men and women, aged 55-74 years, who were current or former smokers with a smoking history of at least 30 pack-years. It randomly assigned them to receive three annual screens with low-dose helical CT or chest x-ray. Helical CT uses x-rays to obtain a multiple-image scan of the entire chest during a 7- to 15-second breath-hold, whereas a standard chest x-ray produces only a single image of the chest from a sub-second breath-hold.

At the time of the Oct. 20, 2010 analysis, 354 deaths from lung cancer had occurred in the CT arm vs. 442 in the chest x-ray group. Approximately 25% of deaths in the NLST were due to lung cancer.

NCI director Harold E. Varmus said the well-designed study used rigorous scientific methods and that its findings could spare countless lives.

“Lung cancer is the leading cause of cancer mortality in the U.S. and throughout the world, so a validated approach that can reduce lung cancer mortality by even 20% has the potential to spare very significant numbers of people from the ravages of this disease,” he said. “But these findings should in no way distract us from continued effort to curtail the use of tobacco, which will remain the major causative factor for lung cancer and several other diseases.”

Like other screening strategies, the use of low-dose helical CT has disadvantages including the cumulative effects of radiation from multiple CT scans, complications among patients who need additional testing to make a definitive lung cancer diagnosis, and the anxiety and added cost associated with investigating incidental findings picked up on CT.

[Editor's note: In 2009, investigators reported that low-dose CT screening was associated with twice the rate of false positives and more unneeded interventions, compared with chest x-ray, in a randomized feasibility trial that preceded the NLST. But low-dose CT also detected twice as many lung cancers as did chest x-ray screens in that study.]

Although the NLST trial cohort was ethnically representative of the high-risk U.S. population, the researchers noted that participants were highly motivated and screened at major medical centers. Thus, the results may not accurately predict the effect of CT screening for other populations.

“What has happened here is that the technology shows you can cut down on lung cancer deaths, the leading cause of cancer mortality, and save nearly as many lives as the number of people who die from breast cancer per year. We as a medical community now need to figure out how to do this in a way that the cost is acceptable to the public,” Dr. Bruce E. Johnson, an official with the American Society of Clinical Oncology and director of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute in Boston, said in a statement.

A more detailed analysis of the NLST results is expected to be published in the coming months, although a paper describing its design and protocol was published by the journal Radiology.

The National Cancer Institute sponsored the study.

A large randomized national trial has provided the first evidence of a significant reduction in lung cancer deaths with a screening test.

The National Lung Screening Trial (NLST) reported a 20.3% reduction in lung cancer mortality among heavy smokers screened with low-dose helical computed tomography (CT), as compared with those given standard chest x-rays. The trial enrolled more than 53,000 older, high-risk individuals.

In addition, deaths from any cause, including lung cancer, were 7% lower among participants screened with low-dose helical CT, also known as spiral CT.

The initial results were released today by the study sponsor, the National Cancer Institute, after the study's independent data and safety monitoring board recommended halting the trial.

“The fact that low-dose helical CT provides a decided benefit is a result that will have implications for screening and management of lung cancer for many years to come,” Dr. Christine Berg, project officer for the lung screening study at the NCI, said in a statement.

Beginning in 2002, the NLST recruited about 53,500 American men and women, aged 55-74 years, who were current or former smokers with a smoking history of at least 30 pack-years. It randomly assigned them to receive three annual screens with low-dose helical CT or chest x-ray. Helical CT uses x-rays to obtain a multiple-image scan of the entire chest during a 7- to 15-second breath-hold, whereas a standard chest x-ray produces only a single image of the chest from a sub-second breath-hold.

At the time of the Oct. 20, 2010 analysis, 354 deaths from lung cancer had occurred in the CT arm vs. 442 in the chest x-ray group. Approximately 25% of deaths in the NLST were due to lung cancer.

NCI director Harold E. Varmus said the well-designed study used rigorous scientific methods and that its findings could spare countless lives.

“Lung cancer is the leading cause of cancer mortality in the U.S. and throughout the world, so a validated approach that can reduce lung cancer mortality by even 20% has the potential to spare very significant numbers of people from the ravages of this disease,” he said. “But these findings should in no way distract us from continued effort to curtail the use of tobacco, which will remain the major causative factor for lung cancer and several other diseases.”

Like other screening strategies, the use of low-dose helical CT has disadvantages including the cumulative effects of radiation from multiple CT scans, complications among patients who need additional testing to make a definitive lung cancer diagnosis, and the anxiety and added cost associated with investigating incidental findings picked up on CT.

[Editor's note: In 2009, investigators reported that low-dose CT screening was associated with twice the rate of false positives and more unneeded interventions, compared with chest x-ray, in a randomized feasibility trial that preceded the NLST. But low-dose CT also detected twice as many lung cancers as did chest x-ray screens in that study.]

Although the NLST trial cohort was ethnically representative of the high-risk U.S. population, the researchers noted that participants were highly motivated and screened at major medical centers. Thus, the results may not accurately predict the effect of CT screening for other populations.

“What has happened here is that the technology shows you can cut down on lung cancer deaths, the leading cause of cancer mortality, and save nearly as many lives as the number of people who die from breast cancer per year. We as a medical community now need to figure out how to do this in a way that the cost is acceptable to the public,” Dr. Bruce E. Johnson, an official with the American Society of Clinical Oncology and director of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute in Boston, said in a statement.

A more detailed analysis of the NLST results is expected to be published in the coming months, although a paper describing its design and protocol was published by the journal Radiology.

The National Cancer Institute sponsored the study.

CHICAGO — Adding eplerenone to standard therapy significantly cut the risk of cardiovascular death and heart failure hospitalization by more than one-third in patients with mild heart failure in the phase III EMPHASIS-HF trial.

The primary composite end point of death from cardiovascular causes or first hospitalization for heart failure occurred in 18% of patients receiving eplerenone (Inspira) and 26% of those given placebo.

This translates into a significant 37% reduction in the primary end point; furthermore, the number of patients needed to treat to prevent one such outcome per year of follow-up was 19, Dr. Faiez Zannad reported in a late-breaking clinical trial report at the meeting. The trial was stopped early, at a median follow-up of 21 months of the planned 48 months, when an interim analysis showed an “overwhelming benefit” with eplerenone.

The use of eplerenone, an aldosterone antagonist, also significantly reduced all-cause mortality by 24%, hospitalization from any cause by 23%, and heart failure hospitalization by 42%.

The benefits were consistent across 20 prespecified subgroups analyzed in the New York Heart Association (NYHA) class II cohort of 2,737 patients.

“We believe that the robustness of these findings, in conjunction with the consistent results from the earlier RALES and EPHESUS trials, provides compelling evidence to change medical practice,” said Dr. Zannad, a cardiologist and professor of therapeutics at Henri Poincaré University of Nancy (France).

Current guidelines recommend the use of aldosterone antagonists in moderate to severe heart failure (NYHA class III and IV) and in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.

The Randomized Aldactone Evaluation Study (RALES) demonstrated a survival advantage with the aldosterone antagonist spironolactone (Aldactone) plus standard therapy in moderate to severe heart failure patients, while the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) did so in the post–MI/heart failure setting.

The current findings have the potential to greatly expand the use of aldosterone antagonists, which are now utilized by fewer than two-thirds of patients with heart failure in the United States with a current indication.

“We have three trials in three distinct groups of heart failure severity which essentially have shown the same results,” Dr. Zannad said in an interview. “This puts this class of drugs on equal ground and if anything, the benefit comes on top of the benefit of angiotensin-converting enzyme inhibitors and beta-blockers.”

The bottom line, he said, is that all patients with a low ejection fraction, provided they have a normal estimated glomerular filtration rate or an EGFR above 30, should be on the three drugs now.

At a press briefing on the study, Dr. Clyde Yancy, immediate past president of the AHA, said that he was enthusiastic about the potential for these drugs to include patients with mild heart failure, but that his enthusiasm is tempered by the risk of hyperkalemia.

“You need to always watch for the presence of hyperkalemia with these drugs, but having said that, the benefit is not modest,” Dr. Yancy said. “This is a very real benefit. And again, two-thirds of patients with an indication are not getting these drugs, and that is what I hope will change.”

Hyperkalemia was reported in 8% of patients treated with eplerenone, compared with 3.7% given placebo, Dr. Zannad said. Treatment discontinuation due to hyperkalemia was reported in 1.1% of eplerenone patients and 0.9% of placebo patients, with hospitalization due to hyperkalemia occurring in 0.3% and 0.2% of patients.

In all, 171 of the 1,364 patients randomized to eplerenone and 213 of the 1,373 patients in the placebo group died. Of these, 147 deaths in the eplerenone group and 185 in the placebo group were due to cardiovascular causes.

Invited discussant Dr. Lynne Warner Stephenson, director of the heart failure program at Brigham and Women's Hospital in Boston, said that EMPHASIS-HF bridges an “awkward gap in our evidence,” but that clinicians need a better understanding of how best to prescribe eplerenone, how the drug works, and how to reduce the life-threatening hyperkalemia associated with these agents before widespread adoption.

She noted that hyperkalemia rates associated with spironolactone in general use have reached 12% in Texas and 10% in Denmark and Norway, and that in Canada the number needed to treat to get one case of hyperkalemia was 13. This led to the recent PEARL-HF trial (Evaluation of RLY5016 in Heart Failure Patients) in which the addition of a new potassium-binding resin (RLY5016) to spironolactone helped lower potassium levels and prevent hyperkalemia in patients with heart failure.

“We have the opportunity and the responsibility to learn from these experiences about how to use aldosterone antagonists safely before we recommend expanding this to the population at risk,” she said.

When asked by reporters whether the data support the use of spironolactone in mild heart failure, Dr. Zannad said that it's possible to extrapolate the results to spironolactone, but that the findings are limited to eplerenone at a dose of 50 mg in patients with NYHA class II heart failure and an ejection fraction of no more than 35%.

During a panel discussion of the study, Dr. Zannad said now that eplerenone has demonstrated efficacy in all symptomatic patients, the next step will be to evaluate the drug in asymptomatic patients and in those with preserved ejection fractions.

The EMPHASIS-HF results were also published in the New England Journal of Medicine (2010 Nov. 14; doi:10.1056/NEJMoa1009492).

The trial was stopped early when an interim analysis showed an “overwhelming benefit” with eplerenone, said Dr. Faiez Zannad.

CHICAGO — Adding eplerenone to standard therapy significantly cut the risk of cardiovascular death and heart failure hospitalization by more than one-third in patients with mild heart failure in the phase III EMPHASIS-HF trial.

The primary composite end point of death from cardiovascular causes or first hospitalization for heart failure occurred in 18% of patients receiving eplerenone (Inspira) and 26% of those given placebo.

This translates into a significant 37% reduction in the primary end point; furthermore, the number of patients needed to treat to prevent one such outcome per year of follow-up was 19, Dr. Faiez Zannad reported in a late-breaking clinical trial report at the meeting. The trial was stopped early, at a median follow-up of 21 months of the planned 48 months, when an interim analysis showed an “overwhelming benefit” with eplerenone.

The use of eplerenone, an aldosterone antagonist, also significantly reduced all-cause mortality by 24%, hospitalization from any cause by 23%, and heart failure hospitalization by 42%.

The benefits were consistent across 20 prespecified subgroups analyzed in the New York Heart Association (NYHA) class II cohort of 2,737 patients.

“We believe that the robustness of these findings, in conjunction with the consistent results from the earlier RALES and EPHESUS trials, provides compelling evidence to change medical practice,” said Dr. Zannad, a cardiologist and professor of therapeutics at Henri Poincaré University of Nancy (France).

Current guidelines recommend the use of aldosterone antagonists in moderate to severe heart failure (NYHA class III and IV) and in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.

The Randomized Aldactone Evaluation Study (RALES) demonstrated a survival advantage with the aldosterone antagonist spironolactone (Aldactone) plus standard therapy in moderate to severe heart failure patients, while the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) did so in the post–MI/heart failure setting.

The current findings have the potential to greatly expand the use of aldosterone antagonists, which are now utilized by fewer than two-thirds of patients with heart failure in the United States with a current indication.

“We have three trials in three distinct groups of heart failure severity which essentially have shown the same results,” Dr. Zannad said in an interview. “This puts this class of drugs on equal ground and if anything, the benefit comes on top of the benefit of angiotensin-converting enzyme inhibitors and beta-blockers.”

The bottom line, he said, is that all patients with a low ejection fraction, provided they have a normal estimated glomerular filtration rate or an EGFR above 30, should be on the three drugs now.

At a press briefing on the study, Dr. Clyde Yancy, immediate past president of the AHA, said that he was enthusiastic about the potential for these drugs to include patients with mild heart failure, but that his enthusiasm is tempered by the risk of hyperkalemia.

“You need to always watch for the presence of hyperkalemia with these drugs, but having said that, the benefit is not modest,” Dr. Yancy said. “This is a very real benefit. And again, two-thirds of patients with an indication are not getting these drugs, and that is what I hope will change.”

Hyperkalemia was reported in 8% of patients treated with eplerenone, compared with 3.7% given placebo, Dr. Zannad said. Treatment discontinuation due to hyperkalemia was reported in 1.1% of eplerenone patients and 0.9% of placebo patients, with hospitalization due to hyperkalemia occurring in 0.3% and 0.2% of patients.

In all, 171 of the 1,364 patients randomized to eplerenone and 213 of the 1,373 patients in the placebo group died. Of these, 147 deaths in the eplerenone group and 185 in the placebo group were due to cardiovascular causes.

Invited discussant Dr. Lynne Warner Stephenson, director of the heart failure program at Brigham and Women's Hospital in Boston, said that EMPHASIS-HF bridges an “awkward gap in our evidence,” but that clinicians need a better understanding of how best to prescribe eplerenone, how the drug works, and how to reduce the life-threatening hyperkalemia associated with these agents before widespread adoption.

She noted that hyperkalemia rates associated with spironolactone in general use have reached 12% in Texas and 10% in Denmark and Norway, and that in Canada the number needed to treat to get one case of hyperkalemia was 13. This led to the recent PEARL-HF trial (Evaluation of RLY5016 in Heart Failure Patients) in which the addition of a new potassium-binding resin (RLY5016) to spironolactone helped lower potassium levels and prevent hyperkalemia in patients with heart failure.

“We have the opportunity and the responsibility to learn from these experiences about how to use aldosterone antagonists safely before we recommend expanding this to the population at risk,” she said.

When asked by reporters whether the data support the use of spironolactone in mild heart failure, Dr. Zannad said that it's possible to extrapolate the results to spironolactone, but that the findings are limited to eplerenone at a dose of 50 mg in patients with NYHA class II heart failure and an ejection fraction of no more than 35%.

During a panel discussion of the study, Dr. Zannad said now that eplerenone has demonstrated efficacy in all symptomatic patients, the next step will be to evaluate the drug in asymptomatic patients and in those with preserved ejection fractions.

The EMPHASIS-HF results were also published in the New England Journal of Medicine (2010 Nov. 14; doi:10.1056/NEJMoa1009492).

The trial was stopped early when an interim analysis showed an “overwhelming benefit” with eplerenone, said Dr. Faiez Zannad.

CHICAGO — Adding eplerenone to standard therapy significantly cut the risk of cardiovascular death and heart failure hospitalization by more than one-third in patients with mild heart failure in the phase III EMPHASIS-HF trial.

The primary composite end point of death from cardiovascular causes or first hospitalization for heart failure occurred in 18% of patients receiving eplerenone (Inspira) and 26% of those given placebo.

This translates into a significant 37% reduction in the primary end point; furthermore, the number of patients needed to treat to prevent one such outcome per year of follow-up was 19, Dr. Faiez Zannad reported in a late-breaking clinical trial report at the meeting. The trial was stopped early, at a median follow-up of 21 months of the planned 48 months, when an interim analysis showed an “overwhelming benefit” with eplerenone.

The use of eplerenone, an aldosterone antagonist, also significantly reduced all-cause mortality by 24%, hospitalization from any cause by 23%, and heart failure hospitalization by 42%.

The benefits were consistent across 20 prespecified subgroups analyzed in the New York Heart Association (NYHA) class II cohort of 2,737 patients.

“We believe that the robustness of these findings, in conjunction with the consistent results from the earlier RALES and EPHESUS trials, provides compelling evidence to change medical practice,” said Dr. Zannad, a cardiologist and professor of therapeutics at Henri Poincaré University of Nancy (France).

Current guidelines recommend the use of aldosterone antagonists in moderate to severe heart failure (NYHA class III and IV) and in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.

The Randomized Aldactone Evaluation Study (RALES) demonstrated a survival advantage with the aldosterone antagonist spironolactone (Aldactone) plus standard therapy in moderate to severe heart failure patients, while the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) did so in the post–MI/heart failure setting.

The current findings have the potential to greatly expand the use of aldosterone antagonists, which are now utilized by fewer than two-thirds of patients with heart failure in the United States with a current indication.

“We have three trials in three distinct groups of heart failure severity which essentially have shown the same results,” Dr. Zannad said in an interview. “This puts this class of drugs on equal ground and if anything, the benefit comes on top of the benefit of angiotensin-converting enzyme inhibitors and beta-blockers.”

The bottom line, he said, is that all patients with a low ejection fraction, provided they have a normal estimated glomerular filtration rate or an EGFR above 30, should be on the three drugs now.

At a press briefing on the study, Dr. Clyde Yancy, immediate past president of the AHA, said that he was enthusiastic about the potential for these drugs to include patients with mild heart failure, but that his enthusiasm is tempered by the risk of hyperkalemia.

“You need to always watch for the presence of hyperkalemia with these drugs, but having said that, the benefit is not modest,” Dr. Yancy said. “This is a very real benefit. And again, two-thirds of patients with an indication are not getting these drugs, and that is what I hope will change.”

Hyperkalemia was reported in 8% of patients treated with eplerenone, compared with 3.7% given placebo, Dr. Zannad said. Treatment discontinuation due to hyperkalemia was reported in 1.1% of eplerenone patients and 0.9% of placebo patients, with hospitalization due to hyperkalemia occurring in 0.3% and 0.2% of patients.

In all, 171 of the 1,364 patients randomized to eplerenone and 213 of the 1,373 patients in the placebo group died. Of these, 147 deaths in the eplerenone group and 185 in the placebo group were due to cardiovascular causes.

Invited discussant Dr. Lynne Warner Stephenson, director of the heart failure program at Brigham and Women's Hospital in Boston, said that EMPHASIS-HF bridges an “awkward gap in our evidence,” but that clinicians need a better understanding of how best to prescribe eplerenone, how the drug works, and how to reduce the life-threatening hyperkalemia associated with these agents before widespread adoption.

She noted that hyperkalemia rates associated with spironolactone in general use have reached 12% in Texas and 10% in Denmark and Norway, and that in Canada the number needed to treat to get one case of hyperkalemia was 13. This led to the recent PEARL-HF trial (Evaluation of RLY5016 in Heart Failure Patients) in which the addition of a new potassium-binding resin (RLY5016) to spironolactone helped lower potassium levels and prevent hyperkalemia in patients with heart failure.

“We have the opportunity and the responsibility to learn from these experiences about how to use aldosterone antagonists safely before we recommend expanding this to the population at risk,” she said.

When asked by reporters whether the data support the use of spironolactone in mild heart failure, Dr. Zannad said that it's possible to extrapolate the results to spironolactone, but that the findings are limited to eplerenone at a dose of 50 mg in patients with NYHA class II heart failure and an ejection fraction of no more than 35%.

During a panel discussion of the study, Dr. Zannad said now that eplerenone has demonstrated efficacy in all symptomatic patients, the next step will be to evaluate the drug in asymptomatic patients and in those with preserved ejection fractions.

The EMPHASIS-HF results were also published in the New England Journal of Medicine (2010 Nov. 14; doi:10.1056/NEJMoa1009492).

The trial was stopped early when an interim analysis showed an “overwhelming benefit” with eplerenone, said Dr. Faiez Zannad.

Major Finding: At 24 weeks, the primary end point of symptomatic recurrence of atrial fibrillation or flutter in patients with paroxysmal AF occurred among 52% of those randomized to prescription omega-3 and 48% of those given placebo.

Data Source: Double-blind, prospective randomized trial of 663 patients with paroxysmal or persistent atrial fibrillation.

Disclosures: GlaxoSmithKline funded the P-OM3 trial. Dr. Kowey has served as a consultant for Reliant Pharmaceuticals and GSK. Dr. Albert disclosed consulting fees and honoraria from Novartis and research grants from Siemens and St. Jude Medical.

CHICAGO — High-dose, prescription omega-3 fatty acids did no better than placebo in preventing the recurrence of symptomatic paroxysmal atrial fibrillation episodes in the P-OM3 trial.

At 24 weeks, the primary end point of symptomatic recurrence of atrial fibrillation (AF) or flutter in patients with paroxysmal AF occurred in 52% of those receiving prescription omega-3 and 48% of those given placebo, a nonsignificant difference.

Those results were consistent across all prespecified subgroups, including age; gender; smoking status; and use of ACE inhibitors, angiotensin II receptor blockers, or statins, Dr. Peter R. Kowey reported.

In addition, the median annualized numbers of AF/flutter rescue episodes were similar: 2.17 in the placebo group vs. 2.24 in the prescription omega-3 group.

Patients with symptomatic paroxysmal AF made up the majority (82%) of the 663-patient trial, as this group was thought most likely to respond to omega-3 polyunsaturated fatty acids.

All patients were without substantial structural heart disease and in normal sinus rhythm at baseline without the use of antiarrhythmic drugs.

Secondary analyses showed no statistically significant differences in the rates of symptomatic AF or flutter among patients with persistent AF treated with prescription omega-3 (50%) or placebo (33%), and between treatment groups when both the paroxysmal and persistent AF patients were combined (52% vs. 46%, respectively), he said.

Although previous trials have produced mixed results regarding the efficacy of omega-3 fatty acids in atrial fibrillation, the current trial “demonstrated incontrovertibly” that patients with paroxysmal AF who received this drug did no better than those who received placebo, Dr. Kowey, chief of cardiovascular disease at Main Line Health, Lankenau Hospital in Wynnewood, Pa., said during a press briefing.

Dr. Christine Albert of Brigham and Women's Hospital in Boston, an invited discussant, said that the current data are sorely needed because of the large number of patients taking omega-3 fatty acids, but that patients should wait before abandoning the popular drug.

She pointed out that observational studies of fish intake and AF have shown a benefit in elderly patients as well as a potentially negative effect in younger patients,. Those results indicate that omega-3 fatty acids may have different effects in different patient populations.

This raises the question of whether subtypes of patients with AF may still benefit from omega-3 fatty acids, including people with post-operative AF, older patients with chronic heart failure or structural heart disease, and those with persistent or chronic AF, Dr. Albert said.

The phase III OPERA trial is currently testing whether perioperative omega-3 fatty acids will decrease the occurrence of postoperative AF, compared with placebo, in patients undergoing cardiac surgery.

Dr. Albert also noted that the P-OM3 trial did not address the longer-term effects of omega-3, whether lower doses could be more effective, and whether omega-3 fatty acids could be useful in the primary prevention of AF.

“The take-home point is that right now we really don't have any evidence that these omega-3 fatty acids prevent symptomatic atrial fibrillation in paroxysmal patients,” Dr. Albert said. “I do think there is a role for further large-scale randomized trials, which are ongoing.”

As expected, prescription-grade omega-3 was extremely well tolerated in P-OM3, with a very low incidence of any adverse event and no difference in rates of serious adverse events, Dr. Kowey said. In all, 5% of the placebo group and 4% of the omega-3 group discontinued therapy because of an adverse event.

The trial randomized 542 patients with symptomatic paroxysmal AF and 121 patients with persistent AF to 8 g/day of prescription omega-3 for 7 days and 4 g/day thereafter or placebo. Of these, 527 paroxysmal patients and 118 persistent AF patients were evaluable, with the remainder lost to follow-up, excluded for lack of ECG monitoring data, or withdrawing.

Major Finding: At 24 weeks, the primary end point of symptomatic recurrence of atrial fibrillation or flutter in patients with paroxysmal AF occurred among 52% of those randomized to prescription omega-3 and 48% of those given placebo.

Data Source: Double-blind, prospective randomized trial of 663 patients with paroxysmal or persistent atrial fibrillation.

Disclosures: GlaxoSmithKline funded the P-OM3 trial. Dr. Kowey has served as a consultant for Reliant Pharmaceuticals and GSK. Dr. Albert disclosed consulting fees and honoraria from Novartis and research grants from Siemens and St. Jude Medical.

CHICAGO — High-dose, prescription omega-3 fatty acids did no better than placebo in preventing the recurrence of symptomatic paroxysmal atrial fibrillation episodes in the P-OM3 trial.

At 24 weeks, the primary end point of symptomatic recurrence of atrial fibrillation (AF) or flutter in patients with paroxysmal AF occurred in 52% of those receiving prescription omega-3 and 48% of those given placebo, a nonsignificant difference.

Those results were consistent across all prespecified subgroups, including age; gender; smoking status; and use of ACE inhibitors, angiotensin II receptor blockers, or statins, Dr. Peter R. Kowey reported.

In addition, the median annualized numbers of AF/flutter rescue episodes were similar: 2.17 in the placebo group vs. 2.24 in the prescription omega-3 group.

Patients with symptomatic paroxysmal AF made up the majority (82%) of the 663-patient trial, as this group was thought most likely to respond to omega-3 polyunsaturated fatty acids.

All patients were without substantial structural heart disease and in normal sinus rhythm at baseline without the use of antiarrhythmic drugs.

Secondary analyses showed no statistically significant differences in the rates of symptomatic AF or flutter among patients with persistent AF treated with prescription omega-3 (50%) or placebo (33%), and between treatment groups when both the paroxysmal and persistent AF patients were combined (52% vs. 46%, respectively), he said.

Although previous trials have produced mixed results regarding the efficacy of omega-3 fatty acids in atrial fibrillation, the current trial “demonstrated incontrovertibly” that patients with paroxysmal AF who received this drug did no better than those who received placebo, Dr. Kowey, chief of cardiovascular disease at Main Line Health, Lankenau Hospital in Wynnewood, Pa., said during a press briefing.

Dr. Christine Albert of Brigham and Women's Hospital in Boston, an invited discussant, said that the current data are sorely needed because of the large number of patients taking omega-3 fatty acids, but that patients should wait before abandoning the popular drug.

She pointed out that observational studies of fish intake and AF have shown a benefit in elderly patients as well as a potentially negative effect in younger patients,. Those results indicate that omega-3 fatty acids may have different effects in different patient populations.

This raises the question of whether subtypes of patients with AF may still benefit from omega-3 fatty acids, including people with post-operative AF, older patients with chronic heart failure or structural heart disease, and those with persistent or chronic AF, Dr. Albert said.

The phase III OPERA trial is currently testing whether perioperative omega-3 fatty acids will decrease the occurrence of postoperative AF, compared with placebo, in patients undergoing cardiac surgery.

Dr. Albert also noted that the P-OM3 trial did not address the longer-term effects of omega-3, whether lower doses could be more effective, and whether omega-3 fatty acids could be useful in the primary prevention of AF.

“The take-home point is that right now we really don't have any evidence that these omega-3 fatty acids prevent symptomatic atrial fibrillation in paroxysmal patients,” Dr. Albert said. “I do think there is a role for further large-scale randomized trials, which are ongoing.”

As expected, prescription-grade omega-3 was extremely well tolerated in P-OM3, with a very low incidence of any adverse event and no difference in rates of serious adverse events, Dr. Kowey said. In all, 5% of the placebo group and 4% of the omega-3 group discontinued therapy because of an adverse event.

The trial randomized 542 patients with symptomatic paroxysmal AF and 121 patients with persistent AF to 8 g/day of prescription omega-3 for 7 days and 4 g/day thereafter or placebo. Of these, 527 paroxysmal patients and 118 persistent AF patients were evaluable, with the remainder lost to follow-up, excluded for lack of ECG monitoring data, or withdrawing.

Major Finding: At 24 weeks, the primary end point of symptomatic recurrence of atrial fibrillation or flutter in patients with paroxysmal AF occurred among 52% of those randomized to prescription omega-3 and 48% of those given placebo.

Data Source: Double-blind, prospective randomized trial of 663 patients with paroxysmal or persistent atrial fibrillation.

Disclosures: GlaxoSmithKline funded the P-OM3 trial. Dr. Kowey has served as a consultant for Reliant Pharmaceuticals and GSK. Dr. Albert disclosed consulting fees and honoraria from Novartis and research grants from Siemens and St. Jude Medical.

CHICAGO — High-dose, prescription omega-3 fatty acids did no better than placebo in preventing the recurrence of symptomatic paroxysmal atrial fibrillation episodes in the P-OM3 trial.

At 24 weeks, the primary end point of symptomatic recurrence of atrial fibrillation (AF) or flutter in patients with paroxysmal AF occurred in 52% of those receiving prescription omega-3 and 48% of those given placebo, a nonsignificant difference.

Those results were consistent across all prespecified subgroups, including age; gender; smoking status; and use of ACE inhibitors, angiotensin II receptor blockers, or statins, Dr. Peter R. Kowey reported.

In addition, the median annualized numbers of AF/flutter rescue episodes were similar: 2.17 in the placebo group vs. 2.24 in the prescription omega-3 group.

Patients with symptomatic paroxysmal AF made up the majority (82%) of the 663-patient trial, as this group was thought most likely to respond to omega-3 polyunsaturated fatty acids.

All patients were without substantial structural heart disease and in normal sinus rhythm at baseline without the use of antiarrhythmic drugs.

Secondary analyses showed no statistically significant differences in the rates of symptomatic AF or flutter among patients with persistent AF treated with prescription omega-3 (50%) or placebo (33%), and between treatment groups when both the paroxysmal and persistent AF patients were combined (52% vs. 46%, respectively), he said.

Although previous trials have produced mixed results regarding the efficacy of omega-3 fatty acids in atrial fibrillation, the current trial “demonstrated incontrovertibly” that patients with paroxysmal AF who received this drug did no better than those who received placebo, Dr. Kowey, chief of cardiovascular disease at Main Line Health, Lankenau Hospital in Wynnewood, Pa., said during a press briefing.

Dr. Christine Albert of Brigham and Women's Hospital in Boston, an invited discussant, said that the current data are sorely needed because of the large number of patients taking omega-3 fatty acids, but that patients should wait before abandoning the popular drug.

She pointed out that observational studies of fish intake and AF have shown a benefit in elderly patients as well as a potentially negative effect in younger patients,. Those results indicate that omega-3 fatty acids may have different effects in different patient populations.

This raises the question of whether subtypes of patients with AF may still benefit from omega-3 fatty acids, including people with post-operative AF, older patients with chronic heart failure or structural heart disease, and those with persistent or chronic AF, Dr. Albert said.

The phase III OPERA trial is currently testing whether perioperative omega-3 fatty acids will decrease the occurrence of postoperative AF, compared with placebo, in patients undergoing cardiac surgery.

Dr. Albert also noted that the P-OM3 trial did not address the longer-term effects of omega-3, whether lower doses could be more effective, and whether omega-3 fatty acids could be useful in the primary prevention of AF.

“The take-home point is that right now we really don't have any evidence that these omega-3 fatty acids prevent symptomatic atrial fibrillation in paroxysmal patients,” Dr. Albert said. “I do think there is a role for further large-scale randomized trials, which are ongoing.”

As expected, prescription-grade omega-3 was extremely well tolerated in P-OM3, with a very low incidence of any adverse event and no difference in rates of serious adverse events, Dr. Kowey said. In all, 5% of the placebo group and 4% of the omega-3 group discontinued therapy because of an adverse event.

The trial randomized 542 patients with symptomatic paroxysmal AF and 121 patients with persistent AF to 8 g/day of prescription omega-3 for 7 days and 4 g/day thereafter or placebo. Of these, 527 paroxysmal patients and 118 persistent AF patients were evaluable, with the remainder lost to follow-up, excluded for lack of ECG monitoring data, or withdrawing.

Major Finding: SPI-positive patients were significantly more likely than were SPI-negative patients to have a depressive disorder diagnosis (80% vs. 19%, respectively), previous psychiatric history (90% vs. 27%), and to currently use psychotropic medications (50% vs. 13%), all risk factors for suicide.

Data Source: Analysis of 58 consecutive adults at an inpatient epilepsy service.

Disclosures: The authors disclosed no conflicts of interest.

CHICAGO – A past psychiatric history, depressive disorder diagnosis, and current use of psychotropic medications were significantly associated with a higher potential for suicidal behavior.

“Suicide risk in patients with epilepsy reflects the higher incidence of psychiatric comorbidity in this population rather than any neurologic or demographic factor,” reported Robert C. Doss, Psy.D., and Dr. Patricia E. Penovich, of the Minnesota Epilepsy Group in St. Paul. This finding confirms what has been established in previous research.

About 30% of people with epilepsy have a major depressive disorder, and research suggests that about 50% of the time they are never treated for the problem, according to the Epilepsy Foundation.

Moreover, the suicide rate in persons with epilepsy is on average 12%, compared with about 1% in the general population (Epilepsy Behav. 2003;4:[Suppl. 3]S31–8). Given the prevalence of this problem and the 2008 warning by the Food and Drug Administration regarding the association between suicidality and antiepileptic drugs, further understanding of this matter is urgently needed, Dr. Doss and Dr. Penovich reported in a poster at the conference.

Upon admission, the 58 patients in the sample underwent long-term video-EEG, neuropsychological testing, personality assessment using the Personality Assessment Inventory, social work evaluation, and if indicated, psychology and/or psychiatry consultation.

Ten patients (mean age, 36 years) showed clinical elevations on the inventory's Suicide Potential Index (SPI) and 48 patients (mean age, 38 years) did not. The SPI consists of 20 features on the inventory that tap what are described as key risk factors for completed suicide in the suicidality literature.

Patients with a positive SPI were significantly more likely than were those with a negative SPI to have a depressive disorder diagnosis (80% vs. 19%, respectively), to have a previous psychiatric history (90% vs. 27%), and to currently use psychotropic medications (50% vs. 13%), Dr. Doss and Dr. Penovich reported.

No other variables, including age, gender, education, duration of epilepsy, temporal lobe epilepsy, complex partial seizures, other neurologic history, epilepsy surgery, number of anti-epileptic drugs, seizure frequency, anxiety disorder diagnosis, or cognitive status were found to significantly differentiate the two groups.

The lifetime prevalence rate of suicide and suicide attempts has been reported to be particularly high in patients with temporal lobe epilepsy and those who have had epilepsy surgery when compared with the general population, but neither risk factor stood out in the current analysis. Temporal lobe epilepsy was present in 30% of the SPI-positive group, compared with 55% of the SPI-negative group, and epilepsy surgery in 20%, compared with 10%.

Also, the number of antiepileptic drugs was similar in both groups at 2.0 and 1.8.

“Routine care of persons with epilepsy should include screening for both current and past psychiatric symptoms,” the authors concluded. “Particular attention should be paid to persons with epilepsy with a clear psychiatric history.”

The conference was jointly sponsored by the EDDC and the office of continuing education of Elsevier, which owns this news organization.

Major Finding: SPI-positive patients were significantly more likely than were SPI-negative patients to have a depressive disorder diagnosis (80% vs. 19%, respectively), previous psychiatric history (90% vs. 27%), and to currently use psychotropic medications (50% vs. 13%), all risk factors for suicide.

Data Source: Analysis of 58 consecutive adults at an inpatient epilepsy service.

Disclosures: The authors disclosed no conflicts of interest.

CHICAGO – A past psychiatric history, depressive disorder diagnosis, and current use of psychotropic medications were significantly associated with a higher potential for suicidal behavior.

“Suicide risk in patients with epilepsy reflects the higher incidence of psychiatric comorbidity in this population rather than any neurologic or demographic factor,” reported Robert C. Doss, Psy.D., and Dr. Patricia E. Penovich, of the Minnesota Epilepsy Group in St. Paul. This finding confirms what has been established in previous research.

About 30% of people with epilepsy have a major depressive disorder, and research suggests that about 50% of the time they are never treated for the problem, according to the Epilepsy Foundation.

Moreover, the suicide rate in persons with epilepsy is on average 12%, compared with about 1% in the general population (Epilepsy Behav. 2003;4:[Suppl. 3]S31–8). Given the prevalence of this problem and the 2008 warning by the Food and Drug Administration regarding the association between suicidality and antiepileptic drugs, further understanding of this matter is urgently needed, Dr. Doss and Dr. Penovich reported in a poster at the conference.

Upon admission, the 58 patients in the sample underwent long-term video-EEG, neuropsychological testing, personality assessment using the Personality Assessment Inventory, social work evaluation, and if indicated, psychology and/or psychiatry consultation.

Ten patients (mean age, 36 years) showed clinical elevations on the inventory's Suicide Potential Index (SPI) and 48 patients (mean age, 38 years) did not. The SPI consists of 20 features on the inventory that tap what are described as key risk factors for completed suicide in the suicidality literature.

Patients with a positive SPI were significantly more likely than were those with a negative SPI to have a depressive disorder diagnosis (80% vs. 19%, respectively), to have a previous psychiatric history (90% vs. 27%), and to currently use psychotropic medications (50% vs. 13%), Dr. Doss and Dr. Penovich reported.

No other variables, including age, gender, education, duration of epilepsy, temporal lobe epilepsy, complex partial seizures, other neurologic history, epilepsy surgery, number of anti-epileptic drugs, seizure frequency, anxiety disorder diagnosis, or cognitive status were found to significantly differentiate the two groups.

The lifetime prevalence rate of suicide and suicide attempts has been reported to be particularly high in patients with temporal lobe epilepsy and those who have had epilepsy surgery when compared with the general population, but neither risk factor stood out in the current analysis. Temporal lobe epilepsy was present in 30% of the SPI-positive group, compared with 55% of the SPI-negative group, and epilepsy surgery in 20%, compared with 10%.

Also, the number of antiepileptic drugs was similar in both groups at 2.0 and 1.8.

“Routine care of persons with epilepsy should include screening for both current and past psychiatric symptoms,” the authors concluded. “Particular attention should be paid to persons with epilepsy with a clear psychiatric history.”

The conference was jointly sponsored by the EDDC and the office of continuing education of Elsevier, which owns this news organization.

Major Finding: SPI-positive patients were significantly more likely than were SPI-negative patients to have a depressive disorder diagnosis (80% vs. 19%, respectively), previous psychiatric history (90% vs. 27%), and to currently use psychotropic medications (50% vs. 13%), all risk factors for suicide.

Data Source: Analysis of 58 consecutive adults at an inpatient epilepsy service.

Disclosures: The authors disclosed no conflicts of interest.

CHICAGO – A past psychiatric history, depressive disorder diagnosis, and current use of psychotropic medications were significantly associated with a higher potential for suicidal behavior.

“Suicide risk in patients with epilepsy reflects the higher incidence of psychiatric comorbidity in this population rather than any neurologic or demographic factor,” reported Robert C. Doss, Psy.D., and Dr. Patricia E. Penovich, of the Minnesota Epilepsy Group in St. Paul. This finding confirms what has been established in previous research.

About 30% of people with epilepsy have a major depressive disorder, and research suggests that about 50% of the time they are never treated for the problem, according to the Epilepsy Foundation.

Moreover, the suicide rate in persons with epilepsy is on average 12%, compared with about 1% in the general population (Epilepsy Behav. 2003;4:[Suppl. 3]S31–8). Given the prevalence of this problem and the 2008 warning by the Food and Drug Administration regarding the association between suicidality and antiepileptic drugs, further understanding of this matter is urgently needed, Dr. Doss and Dr. Penovich reported in a poster at the conference.

Upon admission, the 58 patients in the sample underwent long-term video-EEG, neuropsychological testing, personality assessment using the Personality Assessment Inventory, social work evaluation, and if indicated, psychology and/or psychiatry consultation.

Ten patients (mean age, 36 years) showed clinical elevations on the inventory's Suicide Potential Index (SPI) and 48 patients (mean age, 38 years) did not. The SPI consists of 20 features on the inventory that tap what are described as key risk factors for completed suicide in the suicidality literature.

Patients with a positive SPI were significantly more likely than were those with a negative SPI to have a depressive disorder diagnosis (80% vs. 19%, respectively), to have a previous psychiatric history (90% vs. 27%), and to currently use psychotropic medications (50% vs. 13%), Dr. Doss and Dr. Penovich reported.

No other variables, including age, gender, education, duration of epilepsy, temporal lobe epilepsy, complex partial seizures, other neurologic history, epilepsy surgery, number of anti-epileptic drugs, seizure frequency, anxiety disorder diagnosis, or cognitive status were found to significantly differentiate the two groups.

The lifetime prevalence rate of suicide and suicide attempts has been reported to be particularly high in patients with temporal lobe epilepsy and those who have had epilepsy surgery when compared with the general population, but neither risk factor stood out in the current analysis. Temporal lobe epilepsy was present in 30% of the SPI-positive group, compared with 55% of the SPI-negative group, and epilepsy surgery in 20%, compared with 10%.

Also, the number of antiepileptic drugs was similar in both groups at 2.0 and 1.8.

“Routine care of persons with epilepsy should include screening for both current and past psychiatric symptoms,” the authors concluded. “Particular attention should be paid to persons with epilepsy with a clear psychiatric history.”

The conference was jointly sponsored by the EDDC and the office of continuing education of Elsevier, which owns this news organization.