AHA Scientific Sessions 2012

LOS ANGELES – Patients with a patent foramen ovale and an implanted defibrillator or pacemaker may be good candidates for targeted closure, based on a review of more than 6,000 patients.

During an average follow-up of nearly 5 years, patients with a PFO who received an implantable cardioverter defibrillator (ICD) or a permanent pacemaker were more than fourfold more likely to develop stroke or transient ischemic attack (TIA) compared with implanted device recipients who did not have a PFO, Dr. Christopher V. DeSimone said at the annual scientific sessions of the American Heart Association.

"We think that this is a high-risk population that might benefit from PFO closure," said Dr. DeSimone, an internal medicine physician at the Mayo Clinic in Rochester, Minn. He acknowledged the poor efficacy of PFO closure for stroke prevention in several recent randomized trials, but noted that patients with a PFO who receive an ICD or permanent pacemaker may constitute a special subgroup that stands to benefit from PFO closure. "If a patient has a right atrial or ventricular lead and a clot forms and sits there next to the PFO, they would be at high risk" for a stroke or TIA, he said in an interview. In fact, trials that have assessed the efficacy of PFO closure explicitly excluded patients with permanent pacemakers as well as many ICD recipients because of their substantially impaired left ventricular function, such as in the CLOSURE I trial (N. Engl. J. Med. 2012;366:991-9). "This needs to be studied prospectively," he added, noting that his study was limited by being retrospective.

Dr. DeSimone and his associates reviewed 6,086 patients who received an ICD or permanent pacemaker at the Mayo Clinic during January 2000 to October 2010. The group included 375 patients with PFOs. Average age of the patients was 67 years; nearly two-thirds were men. About 15% had a history of stroke or TIA, about 44% had atrial fibrillation, and their average CHA₂D₂-VASc score was 3.1.

During an average follow-up of 4.7 years, the incidence of stroke or TIA was 11% in the PFO patients and 2% in the patients without a PFO. In a multivariate analysis that controlled for baseline demographic and clinical differences, including atrial fibrillation and aspirin and warfarin use, patients with a PFO were 4.6-fold more likely to have a stroke or TIA than were patients without a PFO, a statistically significant difference.

Additional analyses showed that the stroke and TIA rate remained significantly elevated in the PFO patients regardless of whether patients were on treatment with aspirin or on warfarin, and also regardless of whether or not they were older than age 65 or had a history of stroke or TIA, and regardless of whether they had a low or high CHA₂D₂-VASc score, Dr. DeSimone said. They saw no significant link between a PFO present and all-cause mortality.

The PFO-related difference in the incidence of stroke and TIA first became apparent about 1 year after device placement. The event curves continued to diverge more and more over time. Micro-emboli that originate on the device leads may pass through the PFO and into pulmonary circulation, causing increased pulmonary-artery pressures during the year after device placement. The increased right-sided pressure then favors a right-to-left shunt and increased embolization.

The stroke risk in this analysis may have underestimated the true risk because the methods used to find PFOs and stroke may not have been optimal.

Dr. Desimone had no disclosures.

m.zoler@elsevier.com

LOS ANGELES – Patients with a patent foramen ovale and an implanted defibrillator or pacemaker may be good candidates for targeted closure, based on a review of more than 6,000 patients.

During an average follow-up of nearly 5 years, patients with a PFO who received an implantable cardioverter defibrillator (ICD) or a permanent pacemaker were more than fourfold more likely to develop stroke or transient ischemic attack (TIA) compared with implanted device recipients who did not have a PFO, Dr. Christopher V. DeSimone said at the annual scientific sessions of the American Heart Association.

"We think that this is a high-risk population that might benefit from PFO closure," said Dr. DeSimone, an internal medicine physician at the Mayo Clinic in Rochester, Minn. He acknowledged the poor efficacy of PFO closure for stroke prevention in several recent randomized trials, but noted that patients with a PFO who receive an ICD or permanent pacemaker may constitute a special subgroup that stands to benefit from PFO closure. "If a patient has a right atrial or ventricular lead and a clot forms and sits there next to the PFO, they would be at high risk" for a stroke or TIA, he said in an interview. In fact, trials that have assessed the efficacy of PFO closure explicitly excluded patients with permanent pacemakers as well as many ICD recipients because of their substantially impaired left ventricular function, such as in the CLOSURE I trial (N. Engl. J. Med. 2012;366:991-9). "This needs to be studied prospectively," he added, noting that his study was limited by being retrospective.

Dr. DeSimone and his associates reviewed 6,086 patients who received an ICD or permanent pacemaker at the Mayo Clinic during January 2000 to October 2010. The group included 375 patients with PFOs. Average age of the patients was 67 years; nearly two-thirds were men. About 15% had a history of stroke or TIA, about 44% had atrial fibrillation, and their average CHA₂D₂-VASc score was 3.1.

During an average follow-up of 4.7 years, the incidence of stroke or TIA was 11% in the PFO patients and 2% in the patients without a PFO. In a multivariate analysis that controlled for baseline demographic and clinical differences, including atrial fibrillation and aspirin and warfarin use, patients with a PFO were 4.6-fold more likely to have a stroke or TIA than were patients without a PFO, a statistically significant difference.

Additional analyses showed that the stroke and TIA rate remained significantly elevated in the PFO patients regardless of whether patients were on treatment with aspirin or on warfarin, and also regardless of whether or not they were older than age 65 or had a history of stroke or TIA, and regardless of whether they had a low or high CHA₂D₂-VASc score, Dr. DeSimone said. They saw no significant link between a PFO present and all-cause mortality.

The PFO-related difference in the incidence of stroke and TIA first became apparent about 1 year after device placement. The event curves continued to diverge more and more over time. Micro-emboli that originate on the device leads may pass through the PFO and into pulmonary circulation, causing increased pulmonary-artery pressures during the year after device placement. The increased right-sided pressure then favors a right-to-left shunt and increased embolization.

The stroke risk in this analysis may have underestimated the true risk because the methods used to find PFOs and stroke may not have been optimal.

Dr. Desimone had no disclosures.

m.zoler@elsevier.com

LOS ANGELES – Patients with a patent foramen ovale and an implanted defibrillator or pacemaker may be good candidates for targeted closure, based on a review of more than 6,000 patients.

During an average follow-up of nearly 5 years, patients with a PFO who received an implantable cardioverter defibrillator (ICD) or a permanent pacemaker were more than fourfold more likely to develop stroke or transient ischemic attack (TIA) compared with implanted device recipients who did not have a PFO, Dr. Christopher V. DeSimone said at the annual scientific sessions of the American Heart Association.

"We think that this is a high-risk population that might benefit from PFO closure," said Dr. DeSimone, an internal medicine physician at the Mayo Clinic in Rochester, Minn. He acknowledged the poor efficacy of PFO closure for stroke prevention in several recent randomized trials, but noted that patients with a PFO who receive an ICD or permanent pacemaker may constitute a special subgroup that stands to benefit from PFO closure. "If a patient has a right atrial or ventricular lead and a clot forms and sits there next to the PFO, they would be at high risk" for a stroke or TIA, he said in an interview. In fact, trials that have assessed the efficacy of PFO closure explicitly excluded patients with permanent pacemakers as well as many ICD recipients because of their substantially impaired left ventricular function, such as in the CLOSURE I trial (N. Engl. J. Med. 2012;366:991-9). "This needs to be studied prospectively," he added, noting that his study was limited by being retrospective.

Dr. DeSimone and his associates reviewed 6,086 patients who received an ICD or permanent pacemaker at the Mayo Clinic during January 2000 to October 2010. The group included 375 patients with PFOs. Average age of the patients was 67 years; nearly two-thirds were men. About 15% had a history of stroke or TIA, about 44% had atrial fibrillation, and their average CHA₂D₂-VASc score was 3.1.

During an average follow-up of 4.7 years, the incidence of stroke or TIA was 11% in the PFO patients and 2% in the patients without a PFO. In a multivariate analysis that controlled for baseline demographic and clinical differences, including atrial fibrillation and aspirin and warfarin use, patients with a PFO were 4.6-fold more likely to have a stroke or TIA than were patients without a PFO, a statistically significant difference.

Additional analyses showed that the stroke and TIA rate remained significantly elevated in the PFO patients regardless of whether patients were on treatment with aspirin or on warfarin, and also regardless of whether or not they were older than age 65 or had a history of stroke or TIA, and regardless of whether they had a low or high CHA₂D₂-VASc score, Dr. DeSimone said. They saw no significant link between a PFO present and all-cause mortality.

The PFO-related difference in the incidence of stroke and TIA first became apparent about 1 year after device placement. The event curves continued to diverge more and more over time. Micro-emboli that originate on the device leads may pass through the PFO and into pulmonary circulation, causing increased pulmonary-artery pressures during the year after device placement. The increased right-sided pressure then favors a right-to-left shunt and increased embolization.

The stroke risk in this analysis may have underestimated the true risk because the methods used to find PFOs and stroke may not have been optimal.

Dr. Desimone had no disclosures.

m.zoler@elsevier.com

LOS ANGELES – Radial-artery access for percutaneous coronary interventions finally took off in the Unites States starting about 3 years ago, rising from a steady rate of less than 2% of all American coronary interventions done through early 2009 to more than 11% of all coronary procedures by the third quarter of 2011, according to a nationwide registry.

Registry data from more than 2.2 million PCIs done during January 2007–September 2011 also confirmed better safety for PCI with a radial-artery approach, with bleeding and vascular complication rates substantially below those of patients who underwent PCI via a femoral approach. In addition, procedural success showed a small but statistically significant benefit in favor of radial entry for PCI, Dr. Dmitriy N. Feldman reported at the annual scientific sessions of the American Heart Association.

But these advantages seen in observational data plus the rising use of radial access come against a backdrop of radial access’ failure to show any safety or efficacy advantage over femoral access in the largest randomized trial to compare the two approaches, published in 2011.

"The biggest and best randomized, controlled trial that compared femoral and radial for PCI, the RIVAL [Radial Versus Femoral Access for Coronary Angioplasty and Interventions in patients with Acute Coronary Syndromes] trial, showed absolutely no difference in bleeding or clinical outcomes," commented Dr. Eric R. Bates, an interventional cardiologist and professor of medicine at the University of Michigan in Ann Arbor (Lancet 2011;377:1409-23). Seeing differences in the registry data reported by Dr. Feldman "is a classic observational-trial effect. It could all be because of confounding and selection bias," Dr. Bates said in an interview.

The registry data reported at the meeting also documented a continued split among U.S. cardiologists in their use of radial-artery PCI: 20% of the 1,315 U.S. hospitals that contributed data to the registry during the study years did not perform any radial-access procedures, while 13 hospitals (1% of the total) used radial-artery approaches for more than half the PCIs they performed, said Dr. Feldman, an interventional cardiologist at New York-Presbyterian Hospital and Weill Cornell Medical School in New York.

Results from a second study reported at the meeting confirmed the superior safety of radial-artery PCI compared with femoral-artery access in a review of more than 750 patients treated at Ohio State University before and after a program-wide switch to radial-artery access as the default approach for elective PCIs, said Dr. Quinn Capers IV, an interventional cardiologist at Ohio State in Columbus. His comparison of complication rates during a period when few patients underwent PCI by a radial approach with a period shortly after when half the patients had the radial approach showed that this changeover to radial use linked with a greater than 75% drop in the rate of post-PCI myocardial infarctions and cuts by about two-thirds in the rate of blood transfusions and the rate of major access-site complications, Dr. Capers said.

American use of radial-artery PCI began rising sharply in late 2009 because of a "tipping point at that time," commented Dr. Jennifer Tremmel, an interventional cardiologist at Stanford (Calif.) University. "It was driven by fellows. Our fellows [at Stanford University] can now do both radial and femoral access" equally well, which allows them to better match their approach to what works best for the patient and for the procedure the patient will undergo.

"Most coronary interventions today can be done through the radial artery, while other procedures, like transcatheter aortic-valve replacement, use devices that are too large to go through the radial," said Dr. Ian C. Gilchrist, an interventionalist and professor of medicine at Penn State Hershey (Pa.) Medical Center. "There is a best approach for each procedure, but as equipment gets smaller and smaller I think you’ll see less and less of a role for femoral access for routine coronary work.

"Once you get into a period of rapid uptake [with radial-access PCI] it continues until you get up to 70% or 80%," Dr. Gilchrist predicted. "My guess is that radial will continue to rise [in the United States] until it far exceeds the transfemoral approach. That’s been the experience worldwide.

"In the United States there was a 10-year love affair with closure devices; that’s probably why radial didn’t kick up right away. But closure devices are at least $300 apiece, and they have never been shown to make a difference in outcomes. In my mind, transradial is a game changer," Dr. Gilchrist said in an interview. "It’s not just a minor change in the access site. It allows you to really redesign the cath lab – you don’t need all the beds." And it provides a better platform for routinely performing elective PCIs on a same-day discharge basis.

"Femoral closure devices give operators a false sense of security. Statistics show that the femoral closure devices do not reduce complications," said Dr. Christopher J. White, an interventional cardiologist and medical director of the John Ochsner Heart & Vascular Institute in New Orleans. "The prevalence of radials will continue to increase, eventually reaching parity with [the usage rate in] Europe and South American, perhaps in 5-10 years," he said in an interview.

"I first used radial access when I practiced in the United Kingdom for 3 years, but when I returned to America in 1997 I had six partners who were all femoral-access doctors," Dr. White recalled. "Now, 15 years later, three of those doctors are predominantly radialists, two use it occasionally, and the sixth, the oldest, remains stubbornly an exclusive femoralist. It is hard to teach an old dog a new trick, particularly when PCI procedures can result in life-threatening complications. Why should an expert at femoral access become a novice at radial access?" Radial access "is not for every case, and perhaps not for every interventionalist, but younger cardiologists and trainees are the ones changing the balance. The next generation of interventionalists will be the radialists of the future," Dr. White predicted.

Interventionalists "who do 50 or 75 PCIs a year don’t have the time to retrain with radial, and there is no imperative for a 50-year old to switch to radial access to only do PCIs for another 5 or 10 years," said Dr. Bates. Ideally, "radial is something every interventionalist ought to learn to do – it’s a complimentary technique" to femoral access, but he agreed that it will primarily be the interventionalists who become proficient with radial access during training who will drive a change in American practice.

The data Dr. Feldman reported came from the CathPCI Registry of the National Cardiovascular Data Registry, organized and sponsored by the American College of Cardiology. During the nearly 5 years studied, the participating hospitals, about 70% of U.S. centers that perform PCI, treated 2,135,994 patients who underwent PCI via femoral-artery access, and 94,729 who had PCI with radial-artery access. Quarterly rates of radial-access use stood at 1.2% during early 2007, and remained below 2% through the first quarter of 2009, but then began to rise steadily, reaching the highest level so far, 11.4% of all PCIs, in the third quarter of 2011.

The data also showed notable regional variations in PCI access sites, with radial-artery access more widely used in northeastern states. By mid 2011, radial PCI represented about 20% of all PCIs done in the northeastern U.S. region, compared with rates that peaked at about 8%-10% in the West, Midwest, and South.

The analysis also showed that 94.7% of the radial cases and 93.8% of the femoral cases produced procedural success. Bleeding complications affected 2.8% of the radial-access patients, compared with 6.1% of the femoral-access patients. In a multivariate analysis that adjusted for several case-specific differences, PCI done through the radial artery led to a statistically significant 56% reduction in any bleeding complication and a significant 65% reduction in any vascular complication, and a significant 14% increase in procedural success compared with femoral access, Dr. Feldman reported.

Patient subgroups with the biggest reductions in bleeding complications from radial access compared with femoral access were women, patients with ST-elevation myocardial infarctions, and patients who were at least 75 years old.

The data reported by Dr. Capers came from a comparison of post-PCI complications among the 414 patients who underwent PCI at Ohio State during the first quarter of 2010, and the 343 patients who had PCIs performed during the fourth quarter of 2011. During the earlier period, 5% of patients treated with PCI at Ohio State had access via the radial artery, while at the end of 2011 50% of patients had radial-access PCI. This shift in PCI access started in 2010, when the seven attending cardiologists who perform PCIs at Ohio State agreed to all share a "radial-first mindset" for all elective procedures, Dr. Capers said.

The shift linked with statistically significant reductions in the rates of bleeding complications, blood transfusions, and major access-site complications during the first 72 hours following PCI, and also a reduction in post-PCI shock of about two-thirds that just missed statistical significance.

"These data are compelling" as a rationale for broader use of radial-access PCI, Dr. Capers said. "I think our use of radial access will continue to go up. We realize that we should do more radial cases. A lot is driven by the fellows [who know how to perform radial-access PCI] and by patients who ask for it," he said.

Patient preference as well as hospital preference may wind up being the most persuasive arguments in favor of the radial approach, Dr. Bates said.

"There is no question that radial access is more comfortable for patients, and it’s definitely the way to go for people who want same-day discharge from PCI. That’s terrific," and reason enough to favor radial access when it’s appropriate regardless of whether or not it is ever proven to cause less bleeding. Interventionalists are generally more comfortable sending a patient home the same day after elective PCI with radial access instead of femoral access, and that fact alone may be what drives future growth of the radial approach.

"More radial access will facilitate same-day discharge, and that will help save hospital beds for [all types of] patients who need overnight stays," Dr. Bates added. "A lot of hospitals today, like mine [at the University of Michigan], have many days when no spare beds are available. We’re always trying to figure out ways to speed patient turnover. Every hospital wants to grow its volume, and radial access will facilitate freeing hospital beds."

Dr. Feldman has been a consultant to Maquet Cardiovascular and Abbott Vascular. Dr. Capers said that he had no disclosures. Dr. Tremmel has received honoraria as a consultant to Abbott Vascular and Terumo Medical. Dr. Gilchrist has received honoraria from Terumo Medical. Dr. Bates and Dr. White said that they had no disclosures.

m.zoler@elsevier.com

On Twitter @mitchelzoler

LOS ANGELES – Radial-artery access for percutaneous coronary interventions finally took off in the Unites States starting about 3 years ago, rising from a steady rate of less than 2% of all American coronary interventions done through early 2009 to more than 11% of all coronary procedures by the third quarter of 2011, according to a nationwide registry.

Registry data from more than 2.2 million PCIs done during January 2007–September 2011 also confirmed better safety for PCI with a radial-artery approach, with bleeding and vascular complication rates substantially below those of patients who underwent PCI via a femoral approach. In addition, procedural success showed a small but statistically significant benefit in favor of radial entry for PCI, Dr. Dmitriy N. Feldman reported at the annual scientific sessions of the American Heart Association.

But these advantages seen in observational data plus the rising use of radial access come against a backdrop of radial access’ failure to show any safety or efficacy advantage over femoral access in the largest randomized trial to compare the two approaches, published in 2011.

"The biggest and best randomized, controlled trial that compared femoral and radial for PCI, the RIVAL [Radial Versus Femoral Access for Coronary Angioplasty and Interventions in patients with Acute Coronary Syndromes] trial, showed absolutely no difference in bleeding or clinical outcomes," commented Dr. Eric R. Bates, an interventional cardiologist and professor of medicine at the University of Michigan in Ann Arbor (Lancet 2011;377:1409-23). Seeing differences in the registry data reported by Dr. Feldman "is a classic observational-trial effect. It could all be because of confounding and selection bias," Dr. Bates said in an interview.

The registry data reported at the meeting also documented a continued split among U.S. cardiologists in their use of radial-artery PCI: 20% of the 1,315 U.S. hospitals that contributed data to the registry during the study years did not perform any radial-access procedures, while 13 hospitals (1% of the total) used radial-artery approaches for more than half the PCIs they performed, said Dr. Feldman, an interventional cardiologist at New York-Presbyterian Hospital and Weill Cornell Medical School in New York.

Results from a second study reported at the meeting confirmed the superior safety of radial-artery PCI compared with femoral-artery access in a review of more than 750 patients treated at Ohio State University before and after a program-wide switch to radial-artery access as the default approach for elective PCIs, said Dr. Quinn Capers IV, an interventional cardiologist at Ohio State in Columbus. His comparison of complication rates during a period when few patients underwent PCI by a radial approach with a period shortly after when half the patients had the radial approach showed that this changeover to radial use linked with a greater than 75% drop in the rate of post-PCI myocardial infarctions and cuts by about two-thirds in the rate of blood transfusions and the rate of major access-site complications, Dr. Capers said.

American use of radial-artery PCI began rising sharply in late 2009 because of a "tipping point at that time," commented Dr. Jennifer Tremmel, an interventional cardiologist at Stanford (Calif.) University. "It was driven by fellows. Our fellows [at Stanford University] can now do both radial and femoral access" equally well, which allows them to better match their approach to what works best for the patient and for the procedure the patient will undergo.

"Most coronary interventions today can be done through the radial artery, while other procedures, like transcatheter aortic-valve replacement, use devices that are too large to go through the radial," said Dr. Ian C. Gilchrist, an interventionalist and professor of medicine at Penn State Hershey (Pa.) Medical Center. "There is a best approach for each procedure, but as equipment gets smaller and smaller I think you’ll see less and less of a role for femoral access for routine coronary work.

"Once you get into a period of rapid uptake [with radial-access PCI] it continues until you get up to 70% or 80%," Dr. Gilchrist predicted. "My guess is that radial will continue to rise [in the United States] until it far exceeds the transfemoral approach. That’s been the experience worldwide.

"In the United States there was a 10-year love affair with closure devices; that’s probably why radial didn’t kick up right away. But closure devices are at least $300 apiece, and they have never been shown to make a difference in outcomes. In my mind, transradial is a game changer," Dr. Gilchrist said in an interview. "It’s not just a minor change in the access site. It allows you to really redesign the cath lab – you don’t need all the beds." And it provides a better platform for routinely performing elective PCIs on a same-day discharge basis.

"Femoral closure devices give operators a false sense of security. Statistics show that the femoral closure devices do not reduce complications," said Dr. Christopher J. White, an interventional cardiologist and medical director of the John Ochsner Heart & Vascular Institute in New Orleans. "The prevalence of radials will continue to increase, eventually reaching parity with [the usage rate in] Europe and South American, perhaps in 5-10 years," he said in an interview.

"I first used radial access when I practiced in the United Kingdom for 3 years, but when I returned to America in 1997 I had six partners who were all femoral-access doctors," Dr. White recalled. "Now, 15 years later, three of those doctors are predominantly radialists, two use it occasionally, and the sixth, the oldest, remains stubbornly an exclusive femoralist. It is hard to teach an old dog a new trick, particularly when PCI procedures can result in life-threatening complications. Why should an expert at femoral access become a novice at radial access?" Radial access "is not for every case, and perhaps not for every interventionalist, but younger cardiologists and trainees are the ones changing the balance. The next generation of interventionalists will be the radialists of the future," Dr. White predicted.

Interventionalists "who do 50 or 75 PCIs a year don’t have the time to retrain with radial, and there is no imperative for a 50-year old to switch to radial access to only do PCIs for another 5 or 10 years," said Dr. Bates. Ideally, "radial is something every interventionalist ought to learn to do – it’s a complimentary technique" to femoral access, but he agreed that it will primarily be the interventionalists who become proficient with radial access during training who will drive a change in American practice.

The data Dr. Feldman reported came from the CathPCI Registry of the National Cardiovascular Data Registry, organized and sponsored by the American College of Cardiology. During the nearly 5 years studied, the participating hospitals, about 70% of U.S. centers that perform PCI, treated 2,135,994 patients who underwent PCI via femoral-artery access, and 94,729 who had PCI with radial-artery access. Quarterly rates of radial-access use stood at 1.2% during early 2007, and remained below 2% through the first quarter of 2009, but then began to rise steadily, reaching the highest level so far, 11.4% of all PCIs, in the third quarter of 2011.

The data also showed notable regional variations in PCI access sites, with radial-artery access more widely used in northeastern states. By mid 2011, radial PCI represented about 20% of all PCIs done in the northeastern U.S. region, compared with rates that peaked at about 8%-10% in the West, Midwest, and South.

The analysis also showed that 94.7% of the radial cases and 93.8% of the femoral cases produced procedural success. Bleeding complications affected 2.8% of the radial-access patients, compared with 6.1% of the femoral-access patients. In a multivariate analysis that adjusted for several case-specific differences, PCI done through the radial artery led to a statistically significant 56% reduction in any bleeding complication and a significant 65% reduction in any vascular complication, and a significant 14% increase in procedural success compared with femoral access, Dr. Feldman reported.

Patient subgroups with the biggest reductions in bleeding complications from radial access compared with femoral access were women, patients with ST-elevation myocardial infarctions, and patients who were at least 75 years old.

The data reported by Dr. Capers came from a comparison of post-PCI complications among the 414 patients who underwent PCI at Ohio State during the first quarter of 2010, and the 343 patients who had PCIs performed during the fourth quarter of 2011. During the earlier period, 5% of patients treated with PCI at Ohio State had access via the radial artery, while at the end of 2011 50% of patients had radial-access PCI. This shift in PCI access started in 2010, when the seven attending cardiologists who perform PCIs at Ohio State agreed to all share a "radial-first mindset" for all elective procedures, Dr. Capers said.

The shift linked with statistically significant reductions in the rates of bleeding complications, blood transfusions, and major access-site complications during the first 72 hours following PCI, and also a reduction in post-PCI shock of about two-thirds that just missed statistical significance.

"These data are compelling" as a rationale for broader use of radial-access PCI, Dr. Capers said. "I think our use of radial access will continue to go up. We realize that we should do more radial cases. A lot is driven by the fellows [who know how to perform radial-access PCI] and by patients who ask for it," he said.

Patient preference as well as hospital preference may wind up being the most persuasive arguments in favor of the radial approach, Dr. Bates said.

"There is no question that radial access is more comfortable for patients, and it’s definitely the way to go for people who want same-day discharge from PCI. That’s terrific," and reason enough to favor radial access when it’s appropriate regardless of whether or not it is ever proven to cause less bleeding. Interventionalists are generally more comfortable sending a patient home the same day after elective PCI with radial access instead of femoral access, and that fact alone may be what drives future growth of the radial approach.

"More radial access will facilitate same-day discharge, and that will help save hospital beds for [all types of] patients who need overnight stays," Dr. Bates added. "A lot of hospitals today, like mine [at the University of Michigan], have many days when no spare beds are available. We’re always trying to figure out ways to speed patient turnover. Every hospital wants to grow its volume, and radial access will facilitate freeing hospital beds."

Dr. Feldman has been a consultant to Maquet Cardiovascular and Abbott Vascular. Dr. Capers said that he had no disclosures. Dr. Tremmel has received honoraria as a consultant to Abbott Vascular and Terumo Medical. Dr. Gilchrist has received honoraria from Terumo Medical. Dr. Bates and Dr. White said that they had no disclosures.

m.zoler@elsevier.com

On Twitter @mitchelzoler

LOS ANGELES – Radial-artery access for percutaneous coronary interventions finally took off in the Unites States starting about 3 years ago, rising from a steady rate of less than 2% of all American coronary interventions done through early 2009 to more than 11% of all coronary procedures by the third quarter of 2011, according to a nationwide registry.

Registry data from more than 2.2 million PCIs done during January 2007–September 2011 also confirmed better safety for PCI with a radial-artery approach, with bleeding and vascular complication rates substantially below those of patients who underwent PCI via a femoral approach. In addition, procedural success showed a small but statistically significant benefit in favor of radial entry for PCI, Dr. Dmitriy N. Feldman reported at the annual scientific sessions of the American Heart Association.

But these advantages seen in observational data plus the rising use of radial access come against a backdrop of radial access’ failure to show any safety or efficacy advantage over femoral access in the largest randomized trial to compare the two approaches, published in 2011.

"The biggest and best randomized, controlled trial that compared femoral and radial for PCI, the RIVAL [Radial Versus Femoral Access for Coronary Angioplasty and Interventions in patients with Acute Coronary Syndromes] trial, showed absolutely no difference in bleeding or clinical outcomes," commented Dr. Eric R. Bates, an interventional cardiologist and professor of medicine at the University of Michigan in Ann Arbor (Lancet 2011;377:1409-23). Seeing differences in the registry data reported by Dr. Feldman "is a classic observational-trial effect. It could all be because of confounding and selection bias," Dr. Bates said in an interview.

The registry data reported at the meeting also documented a continued split among U.S. cardiologists in their use of radial-artery PCI: 20% of the 1,315 U.S. hospitals that contributed data to the registry during the study years did not perform any radial-access procedures, while 13 hospitals (1% of the total) used radial-artery approaches for more than half the PCIs they performed, said Dr. Feldman, an interventional cardiologist at New York-Presbyterian Hospital and Weill Cornell Medical School in New York.

Results from a second study reported at the meeting confirmed the superior safety of radial-artery PCI compared with femoral-artery access in a review of more than 750 patients treated at Ohio State University before and after a program-wide switch to radial-artery access as the default approach for elective PCIs, said Dr. Quinn Capers IV, an interventional cardiologist at Ohio State in Columbus. His comparison of complication rates during a period when few patients underwent PCI by a radial approach with a period shortly after when half the patients had the radial approach showed that this changeover to radial use linked with a greater than 75% drop in the rate of post-PCI myocardial infarctions and cuts by about two-thirds in the rate of blood transfusions and the rate of major access-site complications, Dr. Capers said.

American use of radial-artery PCI began rising sharply in late 2009 because of a "tipping point at that time," commented Dr. Jennifer Tremmel, an interventional cardiologist at Stanford (Calif.) University. "It was driven by fellows. Our fellows [at Stanford University] can now do both radial and femoral access" equally well, which allows them to better match their approach to what works best for the patient and for the procedure the patient will undergo.

"Most coronary interventions today can be done through the radial artery, while other procedures, like transcatheter aortic-valve replacement, use devices that are too large to go through the radial," said Dr. Ian C. Gilchrist, an interventionalist and professor of medicine at Penn State Hershey (Pa.) Medical Center. "There is a best approach for each procedure, but as equipment gets smaller and smaller I think you’ll see less and less of a role for femoral access for routine coronary work.

"Once you get into a period of rapid uptake [with radial-access PCI] it continues until you get up to 70% or 80%," Dr. Gilchrist predicted. "My guess is that radial will continue to rise [in the United States] until it far exceeds the transfemoral approach. That’s been the experience worldwide.

"In the United States there was a 10-year love affair with closure devices; that’s probably why radial didn’t kick up right away. But closure devices are at least $300 apiece, and they have never been shown to make a difference in outcomes. In my mind, transradial is a game changer," Dr. Gilchrist said in an interview. "It’s not just a minor change in the access site. It allows you to really redesign the cath lab – you don’t need all the beds." And it provides a better platform for routinely performing elective PCIs on a same-day discharge basis.

"Femoral closure devices give operators a false sense of security. Statistics show that the femoral closure devices do not reduce complications," said Dr. Christopher J. White, an interventional cardiologist and medical director of the John Ochsner Heart & Vascular Institute in New Orleans. "The prevalence of radials will continue to increase, eventually reaching parity with [the usage rate in] Europe and South American, perhaps in 5-10 years," he said in an interview.

"I first used radial access when I practiced in the United Kingdom for 3 years, but when I returned to America in 1997 I had six partners who were all femoral-access doctors," Dr. White recalled. "Now, 15 years later, three of those doctors are predominantly radialists, two use it occasionally, and the sixth, the oldest, remains stubbornly an exclusive femoralist. It is hard to teach an old dog a new trick, particularly when PCI procedures can result in life-threatening complications. Why should an expert at femoral access become a novice at radial access?" Radial access "is not for every case, and perhaps not for every interventionalist, but younger cardiologists and trainees are the ones changing the balance. The next generation of interventionalists will be the radialists of the future," Dr. White predicted.

Interventionalists "who do 50 or 75 PCIs a year don’t have the time to retrain with radial, and there is no imperative for a 50-year old to switch to radial access to only do PCIs for another 5 or 10 years," said Dr. Bates. Ideally, "radial is something every interventionalist ought to learn to do – it’s a complimentary technique" to femoral access, but he agreed that it will primarily be the interventionalists who become proficient with radial access during training who will drive a change in American practice.

The data Dr. Feldman reported came from the CathPCI Registry of the National Cardiovascular Data Registry, organized and sponsored by the American College of Cardiology. During the nearly 5 years studied, the participating hospitals, about 70% of U.S. centers that perform PCI, treated 2,135,994 patients who underwent PCI via femoral-artery access, and 94,729 who had PCI with radial-artery access. Quarterly rates of radial-access use stood at 1.2% during early 2007, and remained below 2% through the first quarter of 2009, but then began to rise steadily, reaching the highest level so far, 11.4% of all PCIs, in the third quarter of 2011.

The data also showed notable regional variations in PCI access sites, with radial-artery access more widely used in northeastern states. By mid 2011, radial PCI represented about 20% of all PCIs done in the northeastern U.S. region, compared with rates that peaked at about 8%-10% in the West, Midwest, and South.

The analysis also showed that 94.7% of the radial cases and 93.8% of the femoral cases produced procedural success. Bleeding complications affected 2.8% of the radial-access patients, compared with 6.1% of the femoral-access patients. In a multivariate analysis that adjusted for several case-specific differences, PCI done through the radial artery led to a statistically significant 56% reduction in any bleeding complication and a significant 65% reduction in any vascular complication, and a significant 14% increase in procedural success compared with femoral access, Dr. Feldman reported.

Patient subgroups with the biggest reductions in bleeding complications from radial access compared with femoral access were women, patients with ST-elevation myocardial infarctions, and patients who were at least 75 years old.

The data reported by Dr. Capers came from a comparison of post-PCI complications among the 414 patients who underwent PCI at Ohio State during the first quarter of 2010, and the 343 patients who had PCIs performed during the fourth quarter of 2011. During the earlier period, 5% of patients treated with PCI at Ohio State had access via the radial artery, while at the end of 2011 50% of patients had radial-access PCI. This shift in PCI access started in 2010, when the seven attending cardiologists who perform PCIs at Ohio State agreed to all share a "radial-first mindset" for all elective procedures, Dr. Capers said.

The shift linked with statistically significant reductions in the rates of bleeding complications, blood transfusions, and major access-site complications during the first 72 hours following PCI, and also a reduction in post-PCI shock of about two-thirds that just missed statistical significance.

"These data are compelling" as a rationale for broader use of radial-access PCI, Dr. Capers said. "I think our use of radial access will continue to go up. We realize that we should do more radial cases. A lot is driven by the fellows [who know how to perform radial-access PCI] and by patients who ask for it," he said.

Patient preference as well as hospital preference may wind up being the most persuasive arguments in favor of the radial approach, Dr. Bates said.

"There is no question that radial access is more comfortable for patients, and it’s definitely the way to go for people who want same-day discharge from PCI. That’s terrific," and reason enough to favor radial access when it’s appropriate regardless of whether or not it is ever proven to cause less bleeding. Interventionalists are generally more comfortable sending a patient home the same day after elective PCI with radial access instead of femoral access, and that fact alone may be what drives future growth of the radial approach.

"More radial access will facilitate same-day discharge, and that will help save hospital beds for [all types of] patients who need overnight stays," Dr. Bates added. "A lot of hospitals today, like mine [at the University of Michigan], have many days when no spare beds are available. We’re always trying to figure out ways to speed patient turnover. Every hospital wants to grow its volume, and radial access will facilitate freeing hospital beds."

Dr. Feldman has been a consultant to Maquet Cardiovascular and Abbott Vascular. Dr. Capers said that he had no disclosures. Dr. Tremmel has received honoraria as a consultant to Abbott Vascular and Terumo Medical. Dr. Gilchrist has received honoraria from Terumo Medical. Dr. Bates and Dr. White said that they had no disclosures.

m.zoler@elsevier.com

On Twitter @mitchelzoler

LOS ANGELES – Selected patients can safely undergo percutaneous coronary intervention and go home later the same day, according to experience with a series of 13 patients treated at one U.S. center.

The 13 patients had no cardiac or access-site complications during their first day after leaving the hospital, and by sending patients home 4-6 hours after their PCI the hospital where they were treated gained $1,884 of added margin per patient compared with hospitalizing them overnight, Dr. Quinn Capers IV said at the annual scientific sessions of the American Heart Association.

Hospitals run up fewer direct costs and patients prefer it, said Dr. Capers, an interventional cardiologist at Ohio State University in Columbus. Another key feature of his program is limiting same-day discharge to patients who undergo PCI via radial-artery access. Although other U.S. groups have had positive experiences with same-day discharges following PCI by femoral-artery access (JAMA 2011;306:1461-7), "I feel more comfortable sending home patients after radial-artery access than after femoral access," Dr. Capers said.

The 13-patient experience that Dr. Capers reported from Ohio State is dwarfed by some other programs. For example, Dr. Ian C. Gilchrist, who cochaired the session in which Dr. Capers presented his paper, spoke about his program’s experience with 300-400 PCI patients who went home within a few hours after their procedure.

"We do about 85% of our elective PCI patients same-day," said Dr. Gilchrist, an interventional cardiologist and professor of medicine at Pennsylvania State University, Hershey. "We start off assuming that just about every elective PCI patient is a good candidate to go home the same day," he said in an interview. "Early on I was worried [about same-day discharge], but once we started doing it I realized that it really works." Among the 300-plus patients treated this way by Dr. Gilchrist and his associates, there was one patient who developed a complication in the first 24 hours he was home that potentially would have been identified sooner by keeping the patient hospitalized.

"Our main criteria [for same-day discharge] have been good social support for patients and a relatively nontraumatic procedure. Patients love it. The data on safety and other aspects of PCI speak to the ability to send these patients home after just a few hours of observation," he said.

"We have a nurse practitioner talk with each patient before they come to the hospital to learn more about them, let them know there is a possibility that they can go home the same day, and to ask whether they have good social support. Most patients who don’t go home same day are those with more complicated procedures than we expected and those who don’t have someone who can keep an eye on them during their first night home. We do not a priori exclude patients because of their age, renal function, diabetes, or lung disease.

"About 98% of our same-day patients received radial-artery PCI," Dr. Gilchrist added. "I feel more comfortable sending patients home after a radial intervention. The only transfemorals we have done same day were patients who had a repeat PCI and went home same day the first time and who we couldn’t treat transradially for the repeat procedure. They insisted on going home the same day even after their femoral PCI."

Interventional cardiologists at Ohio State began offering same-day discharge post-PCI to selected patients in 2010. They limit the option to elective patients with preserved left ventricular and renal function and no significant left main or triple vessel disease. Patients also have to live within a 30-minute drive from the hospital and must be willing to return the next day for a brief follow-up assessment. The 13 patients ranged in age from 46 to 83 years.

Dr. Capers and his associates analyzed the direct costs and margins from these 13 patients and for 50 similar patients who had overnight stays in the months before same-day discharge became available. The analysis showed that the contribution margin per patient, calculated by subtracting direct costs from net revenue, was $5,667 for each of the 13 same-day discharges and $3,833 for each of the 50 patients who remained overnight at the hospital following their PCI, a difference of $1,834 per patient in favor of same-day discharges.

Dr. Capers said that he had no disclosures. Dr. Gilchrist has received honoraria from Terumo Medical.

m.zoler@elsevier.com

On Twitter @mitchelzoler

LOS ANGELES – Selected patients can safely undergo percutaneous coronary intervention and go home later the same day, according to experience with a series of 13 patients treated at one U.S. center.

The 13 patients had no cardiac or access-site complications during their first day after leaving the hospital, and by sending patients home 4-6 hours after their PCI the hospital where they were treated gained $1,884 of added margin per patient compared with hospitalizing them overnight, Dr. Quinn Capers IV said at the annual scientific sessions of the American Heart Association.

Hospitals run up fewer direct costs and patients prefer it, said Dr. Capers, an interventional cardiologist at Ohio State University in Columbus. Another key feature of his program is limiting same-day discharge to patients who undergo PCI via radial-artery access. Although other U.S. groups have had positive experiences with same-day discharges following PCI by femoral-artery access (JAMA 2011;306:1461-7), "I feel more comfortable sending home patients after radial-artery access than after femoral access," Dr. Capers said.

The 13-patient experience that Dr. Capers reported from Ohio State is dwarfed by some other programs. For example, Dr. Ian C. Gilchrist, who cochaired the session in which Dr. Capers presented his paper, spoke about his program’s experience with 300-400 PCI patients who went home within a few hours after their procedure.

"We do about 85% of our elective PCI patients same-day," said Dr. Gilchrist, an interventional cardiologist and professor of medicine at Pennsylvania State University, Hershey. "We start off assuming that just about every elective PCI patient is a good candidate to go home the same day," he said in an interview. "Early on I was worried [about same-day discharge], but once we started doing it I realized that it really works." Among the 300-plus patients treated this way by Dr. Gilchrist and his associates, there was one patient who developed a complication in the first 24 hours he was home that potentially would have been identified sooner by keeping the patient hospitalized.

"Our main criteria [for same-day discharge] have been good social support for patients and a relatively nontraumatic procedure. Patients love it. The data on safety and other aspects of PCI speak to the ability to send these patients home after just a few hours of observation," he said.

"We have a nurse practitioner talk with each patient before they come to the hospital to learn more about them, let them know there is a possibility that they can go home the same day, and to ask whether they have good social support. Most patients who don’t go home same day are those with more complicated procedures than we expected and those who don’t have someone who can keep an eye on them during their first night home. We do not a priori exclude patients because of their age, renal function, diabetes, or lung disease.

"About 98% of our same-day patients received radial-artery PCI," Dr. Gilchrist added. "I feel more comfortable sending patients home after a radial intervention. The only transfemorals we have done same day were patients who had a repeat PCI and went home same day the first time and who we couldn’t treat transradially for the repeat procedure. They insisted on going home the same day even after their femoral PCI."

Interventional cardiologists at Ohio State began offering same-day discharge post-PCI to selected patients in 2010. They limit the option to elective patients with preserved left ventricular and renal function and no significant left main or triple vessel disease. Patients also have to live within a 30-minute drive from the hospital and must be willing to return the next day for a brief follow-up assessment. The 13 patients ranged in age from 46 to 83 years.

Dr. Capers and his associates analyzed the direct costs and margins from these 13 patients and for 50 similar patients who had overnight stays in the months before same-day discharge became available. The analysis showed that the contribution margin per patient, calculated by subtracting direct costs from net revenue, was $5,667 for each of the 13 same-day discharges and $3,833 for each of the 50 patients who remained overnight at the hospital following their PCI, a difference of $1,834 per patient in favor of same-day discharges.

Dr. Capers said that he had no disclosures. Dr. Gilchrist has received honoraria from Terumo Medical.

m.zoler@elsevier.com

On Twitter @mitchelzoler

LOS ANGELES – Selected patients can safely undergo percutaneous coronary intervention and go home later the same day, according to experience with a series of 13 patients treated at one U.S. center.

The 13 patients had no cardiac or access-site complications during their first day after leaving the hospital, and by sending patients home 4-6 hours after their PCI the hospital where they were treated gained $1,884 of added margin per patient compared with hospitalizing them overnight, Dr. Quinn Capers IV said at the annual scientific sessions of the American Heart Association.

Hospitals run up fewer direct costs and patients prefer it, said Dr. Capers, an interventional cardiologist at Ohio State University in Columbus. Another key feature of his program is limiting same-day discharge to patients who undergo PCI via radial-artery access. Although other U.S. groups have had positive experiences with same-day discharges following PCI by femoral-artery access (JAMA 2011;306:1461-7), "I feel more comfortable sending home patients after radial-artery access than after femoral access," Dr. Capers said.

The 13-patient experience that Dr. Capers reported from Ohio State is dwarfed by some other programs. For example, Dr. Ian C. Gilchrist, who cochaired the session in which Dr. Capers presented his paper, spoke about his program’s experience with 300-400 PCI patients who went home within a few hours after their procedure.

"We do about 85% of our elective PCI patients same-day," said Dr. Gilchrist, an interventional cardiologist and professor of medicine at Pennsylvania State University, Hershey. "We start off assuming that just about every elective PCI patient is a good candidate to go home the same day," he said in an interview. "Early on I was worried [about same-day discharge], but once we started doing it I realized that it really works." Among the 300-plus patients treated this way by Dr. Gilchrist and his associates, there was one patient who developed a complication in the first 24 hours he was home that potentially would have been identified sooner by keeping the patient hospitalized.

"Our main criteria [for same-day discharge] have been good social support for patients and a relatively nontraumatic procedure. Patients love it. The data on safety and other aspects of PCI speak to the ability to send these patients home after just a few hours of observation," he said.

"We have a nurse practitioner talk with each patient before they come to the hospital to learn more about them, let them know there is a possibility that they can go home the same day, and to ask whether they have good social support. Most patients who don’t go home same day are those with more complicated procedures than we expected and those who don’t have someone who can keep an eye on them during their first night home. We do not a priori exclude patients because of their age, renal function, diabetes, or lung disease.

"About 98% of our same-day patients received radial-artery PCI," Dr. Gilchrist added. "I feel more comfortable sending patients home after a radial intervention. The only transfemorals we have done same day were patients who had a repeat PCI and went home same day the first time and who we couldn’t treat transradially for the repeat procedure. They insisted on going home the same day even after their femoral PCI."

Interventional cardiologists at Ohio State began offering same-day discharge post-PCI to selected patients in 2010. They limit the option to elective patients with preserved left ventricular and renal function and no significant left main or triple vessel disease. Patients also have to live within a 30-minute drive from the hospital and must be willing to return the next day for a brief follow-up assessment. The 13 patients ranged in age from 46 to 83 years.

Dr. Capers and his associates analyzed the direct costs and margins from these 13 patients and for 50 similar patients who had overnight stays in the months before same-day discharge became available. The analysis showed that the contribution margin per patient, calculated by subtracting direct costs from net revenue, was $5,667 for each of the 13 same-day discharges and $3,833 for each of the 50 patients who remained overnight at the hospital following their PCI, a difference of $1,834 per patient in favor of same-day discharges.

Dr. Capers said that he had no disclosures. Dr. Gilchrist has received honoraria from Terumo Medical.

m.zoler@elsevier.com

On Twitter @mitchelzoler

LOS ANGELES – A strategy of catheter ablation–based rhythm control in patients with long-standing persistent atrial fibrillation plus heart failure improved cardiopulmonary exercise capacity, quality of life, and neurohormonal status, compared with pharmacologic rate control in a single-center randomized trial.

The majority of improvement seen in these endpoints in the ARC-HF (Catheter Ablation Versus Medical Rate Control for Atrial Fibrillation in Patients With Heart Failure) trial occurred 3-12 months after the initial ablation procedure, Dr. David G. Jones reported at the annual scientific sessions of the American Heart Association.

"This may reflect progressive amelioration of the heart failure syndrome. And our findings may also have prognostic significance," said Dr. Jones of Imperial College London.

Indeed, although clinical outcomes weren’t included in the relatively small ARC-HF study, they were reported in the recently published 1,620-patient HF-ACTION (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure) trial (Circ. Heart Fail. 2012;5:579-85). And HF-ACTION showed that every 6% increase in peak oxygen uptake (VO₂) was associated with an 8% lower risk of the combined endpoint of cardiovascular mortality or heart failure hospitalization and a 7% reduction in all-cause mortality.

"By comparison, ours was close to a 20% increase in peak VO₂ at 1 year with ablation therapy," Dr. Jones observed.

The ARC-HF trial included 51 patients with continuous persistent atrial fibrillation (AF) for an average of 24 months, symptomatic systolic heart failure, and a left ventricular ejection fraction of 35% or less. Because it has been unclear whether restoration of sinus rhythm or pharmacologic rate control is the optimal management strategy in patients with AF and the common comorbidity of heart failure, the investigators randomized participants to catheter ablation of the arrhythmia or to rate control.

The primary endpoint was the change in peak VO₂ at 12 months from a baseline of roughly 17 mL/kg per minute. Peak VO₂ increased by a mean of 2.0 mL/kg per minute in the 25 patients in the ablation group while declining over time in the rate control group, for an impressive 12-month intergroup difference of 3.07 mL/kg per minute.

The ablation group also displayed significant improvements in quality of life as measured by the Minnesota Living With Heart Failure Questionnaire, as well as neurohormonal status as reflected in a reduction in brain natriuretic peptide levels. Data on other cardiac biomarkers are still being analyzed.

A significant reduction in baseline left atrial dilation was documented in the ablation group at 6 months and maintained at 12 months. The ablation group showed a nonsignificant trend toward improved left ventricular ejection fraction.

Dr. Jones stressed that the ablation procedures were long and challenging. They averaged 333 minutes in duration, including mapping, with fully 80 minutes of fluoroscopy time and 82 minutes of actual ablation.

Seven patients experienced recurrent atrial arrhythmias post ablation; five of them underwent a second ablation procedure and one had a third. The single-procedure success rate in achieving sinus rhythm at 12 months was 72%, with a multiprocedure success rate of 92%.

Of the 26 patients in the rate control group, 2 were in sinus rhythm at 12 months (including 1 patient who crossed over to catheter ablation), and 23 of the remaining 24 were optimally rate controlled, with a resting heart rate below 80 beats per minute and a maximum heart rate below 110 bpm during a 6-minute walk test.

Discussant Dr. Karl-Heinz Kuck called the ARC-HF results "remarkable." So much so, in fact, that he doesn’t think catheter ablation can be recommended for now in patients with long-standing persistent AF and heart failure, because the single-center ARC-HF results are out of step with those reported in observational series. Better, he said, to wait for the results of ongoing, much larger multicenter randomized trials, including CASTLE-AF as well as AMICA, for which he serves as principal investigator.

Among Dr. Kuck’s concerns was the whopping 2.0-mL/kg per minute increase in peak VO₂ reported in ARC-HF. To put that in perspective, the major randomized trials of cardiac resynchronization therapy and cardiac contractility modulation therapy for heart failure achieved increases of only 0.7-1.0 mL/kg per minute.

Also, a recent report from Dr. Kuck and his coinvestigators in the Hamburg Sequential Ablation Group, which involved 202 patients who underwent catheter ablation for long-standing persistent AF, showed only 36% were in sinus rhythm at 12 months after a single procedure and 60% after multiple procedures. Those success rates are substantially lower than in ARC-HF, noted Dr. Kuck, head of the cardiology department at St. Georg Hospital, Hamburg, Germany.

The 5-year success rates in the large Hamburg series were 20% and 45% after single and multiple ablation procedures, respectively. Success rates were far better in patients with a history of less than 2 years of persistent AF than in those who were arrhythmic for longer (J. Am. Coll. Cardiol. 2012;60:1921-9).

The ARC-HF study was supported by research grants from the Royal Brompton & Harefield NHS Foundation Trust. Dr. Jones reported having no financial conflicts. Dr. Kuck is on the speakers bureaus for Biosense Webster, Medtronic, St. Jude Medical, Abbott, Cardiofocus, and Biotronik.

b.jancin@elsevier.com

LOS ANGELES – A strategy of catheter ablation–based rhythm control in patients with long-standing persistent atrial fibrillation plus heart failure improved cardiopulmonary exercise capacity, quality of life, and neurohormonal status, compared with pharmacologic rate control in a single-center randomized trial.

The majority of improvement seen in these endpoints in the ARC-HF (Catheter Ablation Versus Medical Rate Control for Atrial Fibrillation in Patients With Heart Failure) trial occurred 3-12 months after the initial ablation procedure, Dr. David G. Jones reported at the annual scientific sessions of the American Heart Association.

"This may reflect progressive amelioration of the heart failure syndrome. And our findings may also have prognostic significance," said Dr. Jones of Imperial College London.

Indeed, although clinical outcomes weren’t included in the relatively small ARC-HF study, they were reported in the recently published 1,620-patient HF-ACTION (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure) trial (Circ. Heart Fail. 2012;5:579-85). And HF-ACTION showed that every 6% increase in peak oxygen uptake (VO₂) was associated with an 8% lower risk of the combined endpoint of cardiovascular mortality or heart failure hospitalization and a 7% reduction in all-cause mortality.

"By comparison, ours was close to a 20% increase in peak VO₂ at 1 year with ablation therapy," Dr. Jones observed.

The ARC-HF trial included 51 patients with continuous persistent atrial fibrillation (AF) for an average of 24 months, symptomatic systolic heart failure, and a left ventricular ejection fraction of 35% or less. Because it has been unclear whether restoration of sinus rhythm or pharmacologic rate control is the optimal management strategy in patients with AF and the common comorbidity of heart failure, the investigators randomized participants to catheter ablation of the arrhythmia or to rate control.

The primary endpoint was the change in peak VO₂ at 12 months from a baseline of roughly 17 mL/kg per minute. Peak VO₂ increased by a mean of 2.0 mL/kg per minute in the 25 patients in the ablation group while declining over time in the rate control group, for an impressive 12-month intergroup difference of 3.07 mL/kg per minute.

The ablation group also displayed significant improvements in quality of life as measured by the Minnesota Living With Heart Failure Questionnaire, as well as neurohormonal status as reflected in a reduction in brain natriuretic peptide levels. Data on other cardiac biomarkers are still being analyzed.

A significant reduction in baseline left atrial dilation was documented in the ablation group at 6 months and maintained at 12 months. The ablation group showed a nonsignificant trend toward improved left ventricular ejection fraction.

Dr. Jones stressed that the ablation procedures were long and challenging. They averaged 333 minutes in duration, including mapping, with fully 80 minutes of fluoroscopy time and 82 minutes of actual ablation.

Seven patients experienced recurrent atrial arrhythmias post ablation; five of them underwent a second ablation procedure and one had a third. The single-procedure success rate in achieving sinus rhythm at 12 months was 72%, with a multiprocedure success rate of 92%.

Of the 26 patients in the rate control group, 2 were in sinus rhythm at 12 months (including 1 patient who crossed over to catheter ablation), and 23 of the remaining 24 were optimally rate controlled, with a resting heart rate below 80 beats per minute and a maximum heart rate below 110 bpm during a 6-minute walk test.

Discussant Dr. Karl-Heinz Kuck called the ARC-HF results "remarkable." So much so, in fact, that he doesn’t think catheter ablation can be recommended for now in patients with long-standing persistent AF and heart failure, because the single-center ARC-HF results are out of step with those reported in observational series. Better, he said, to wait for the results of ongoing, much larger multicenter randomized trials, including CASTLE-AF as well as AMICA, for which he serves as principal investigator.

Among Dr. Kuck’s concerns was the whopping 2.0-mL/kg per minute increase in peak VO₂ reported in ARC-HF. To put that in perspective, the major randomized trials of cardiac resynchronization therapy and cardiac contractility modulation therapy for heart failure achieved increases of only 0.7-1.0 mL/kg per minute.

Also, a recent report from Dr. Kuck and his coinvestigators in the Hamburg Sequential Ablation Group, which involved 202 patients who underwent catheter ablation for long-standing persistent AF, showed only 36% were in sinus rhythm at 12 months after a single procedure and 60% after multiple procedures. Those success rates are substantially lower than in ARC-HF, noted Dr. Kuck, head of the cardiology department at St. Georg Hospital, Hamburg, Germany.

The 5-year success rates in the large Hamburg series were 20% and 45% after single and multiple ablation procedures, respectively. Success rates were far better in patients with a history of less than 2 years of persistent AF than in those who were arrhythmic for longer (J. Am. Coll. Cardiol. 2012;60:1921-9).

The ARC-HF study was supported by research grants from the Royal Brompton & Harefield NHS Foundation Trust. Dr. Jones reported having no financial conflicts. Dr. Kuck is on the speakers bureaus for Biosense Webster, Medtronic, St. Jude Medical, Abbott, Cardiofocus, and Biotronik.

b.jancin@elsevier.com

LOS ANGELES – A strategy of catheter ablation–based rhythm control in patients with long-standing persistent atrial fibrillation plus heart failure improved cardiopulmonary exercise capacity, quality of life, and neurohormonal status, compared with pharmacologic rate control in a single-center randomized trial.

The majority of improvement seen in these endpoints in the ARC-HF (Catheter Ablation Versus Medical Rate Control for Atrial Fibrillation in Patients With Heart Failure) trial occurred 3-12 months after the initial ablation procedure, Dr. David G. Jones reported at the annual scientific sessions of the American Heart Association.

"This may reflect progressive amelioration of the heart failure syndrome. And our findings may also have prognostic significance," said Dr. Jones of Imperial College London.

Indeed, although clinical outcomes weren’t included in the relatively small ARC-HF study, they were reported in the recently published 1,620-patient HF-ACTION (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure) trial (Circ. Heart Fail. 2012;5:579-85). And HF-ACTION showed that every 6% increase in peak oxygen uptake (VO₂) was associated with an 8% lower risk of the combined endpoint of cardiovascular mortality or heart failure hospitalization and a 7% reduction in all-cause mortality.

"By comparison, ours was close to a 20% increase in peak VO₂ at 1 year with ablation therapy," Dr. Jones observed.

The ARC-HF trial included 51 patients with continuous persistent atrial fibrillation (AF) for an average of 24 months, symptomatic systolic heart failure, and a left ventricular ejection fraction of 35% or less. Because it has been unclear whether restoration of sinus rhythm or pharmacologic rate control is the optimal management strategy in patients with AF and the common comorbidity of heart failure, the investigators randomized participants to catheter ablation of the arrhythmia or to rate control.

The primary endpoint was the change in peak VO₂ at 12 months from a baseline of roughly 17 mL/kg per minute. Peak VO₂ increased by a mean of 2.0 mL/kg per minute in the 25 patients in the ablation group while declining over time in the rate control group, for an impressive 12-month intergroup difference of 3.07 mL/kg per minute.

The ablation group also displayed significant improvements in quality of life as measured by the Minnesota Living With Heart Failure Questionnaire, as well as neurohormonal status as reflected in a reduction in brain natriuretic peptide levels. Data on other cardiac biomarkers are still being analyzed.

A significant reduction in baseline left atrial dilation was documented in the ablation group at 6 months and maintained at 12 months. The ablation group showed a nonsignificant trend toward improved left ventricular ejection fraction.

Dr. Jones stressed that the ablation procedures were long and challenging. They averaged 333 minutes in duration, including mapping, with fully 80 minutes of fluoroscopy time and 82 minutes of actual ablation.

Seven patients experienced recurrent atrial arrhythmias post ablation; five of them underwent a second ablation procedure and one had a third. The single-procedure success rate in achieving sinus rhythm at 12 months was 72%, with a multiprocedure success rate of 92%.

Of the 26 patients in the rate control group, 2 were in sinus rhythm at 12 months (including 1 patient who crossed over to catheter ablation), and 23 of the remaining 24 were optimally rate controlled, with a resting heart rate below 80 beats per minute and a maximum heart rate below 110 bpm during a 6-minute walk test.

Discussant Dr. Karl-Heinz Kuck called the ARC-HF results "remarkable." So much so, in fact, that he doesn’t think catheter ablation can be recommended for now in patients with long-standing persistent AF and heart failure, because the single-center ARC-HF results are out of step with those reported in observational series. Better, he said, to wait for the results of ongoing, much larger multicenter randomized trials, including CASTLE-AF as well as AMICA, for which he serves as principal investigator.

Among Dr. Kuck’s concerns was the whopping 2.0-mL/kg per minute increase in peak VO₂ reported in ARC-HF. To put that in perspective, the major randomized trials of cardiac resynchronization therapy and cardiac contractility modulation therapy for heart failure achieved increases of only 0.7-1.0 mL/kg per minute.

Also, a recent report from Dr. Kuck and his coinvestigators in the Hamburg Sequential Ablation Group, which involved 202 patients who underwent catheter ablation for long-standing persistent AF, showed only 36% were in sinus rhythm at 12 months after a single procedure and 60% after multiple procedures. Those success rates are substantially lower than in ARC-HF, noted Dr. Kuck, head of the cardiology department at St. Georg Hospital, Hamburg, Germany.

The 5-year success rates in the large Hamburg series were 20% and 45% after single and multiple ablation procedures, respectively. Success rates were far better in patients with a history of less than 2 years of persistent AF than in those who were arrhythmic for longer (J. Am. Coll. Cardiol. 2012;60:1921-9).

The ARC-HF study was supported by research grants from the Royal Brompton & Harefield NHS Foundation Trust. Dr. Jones reported having no financial conflicts. Dr. Kuck is on the speakers bureaus for Biosense Webster, Medtronic, St. Jude Medical, Abbott, Cardiofocus, and Biotronik.

b.jancin@elsevier.com

LOS ANGELES – A low-carbohydrate diet produced greater weight loss than did a low-fat diet and reduced systemic inflammation to a similar extent, according to results from a 6-month randomized trial.

The finding that both types of weight-loss diets produced similar reductions in inflammatory markers should help put to rest the concern that a low-carbohydrate diet’s higher fat content might have a negative impact on cardiovascular health, explained Kerry J. Stewart, Ed.D., at the annual scientific sessions of the American Heart Association.

"The concern about the low-carbohydrate diet is coming from the biomedical community. That’s why we did this study, to challenge that whole bias against this approach," explained Dr. Stewart, professor of cardiology and director of clinical research on exercise physiology at Johns Hopkins University, Baltimore.

"We’ve been told for the last 30-40 years, especially by the AHA and other groups, that high fat in the diet raises cholesterol and that all the other things that go along with that have harmful effects on the vasculature," he noted. "But we’ve previously shown no adverse effects on endothelial function or vascular stiffness, [as well as] significant improvements in blood pressure and cholesterol levels, with a low-carbohydrate diet."

Dr. Stewart reported on 60 middle-age overweight or obese patients who participated in a lifestyle intervention consisting of an exercise program plus randomization to a low-fat diet or an isocaloric low-carbohydrate diet.

From a mean baseline body weight of 97.1 kg, patients in the low-carbohydrate-diet group lost an average of 13.1 kg over 6 months, compared with 8.2 kg in the patients on the low-fat diet. From a mean baseline of 43.3%, total body fat dropped by an absolute 6.8% in the low-carb group, a significantly better result than the 4.0% decrease in the low-fat group. From a baseline mean body mass index of 34.2 kg/m², BMI improved by 4.7 kg/m² in the low-carbohydrate diet group, compared with 2.9 kg/m² with the low-fat diet.

High-sensitivity C-reactive protein levels fell by a mean of 1.8 mg/L in both groups, from 5.2 mg/L at baseline. The other markers of systemic inflammation measured in the study – levels of interleukin-6 and tumor necrosis factor-alpha – also improved to a similar degree in both study arms.

"It’s important to keep in mind that this was a weight-loss study. If someone is normal- or underweight and eats this kind of low-carbohydrate diet, I’m not exactly sure what would happen," Dr. Stewart observed. "But in the context of a weight-loss program, it seems like the weight loss is an overwhelming benefit that overcomes any possible risks from eating more fat."

One audience member who had helped run a study of an Atkins-type low-carb/high-fat diet said he and his coinvestigators found deleterious effects on arterial flow-mediated dilation over the course of a year. But Dr. Stewart was unconvinced.

"We’ve looked at that literature. It’s a real mixed bag. Some studies show just what you say, others show just the opposite," he replied. "It’s very hard to draw any conclusions from these feeding studies. We’ve done some of them ourselves and found just the opposite of what you said."

Also, as another audience member pointed out, the low-carbohydrate diet employed in this study wasn’t an Atkins-type diet that’s high in total and saturated fat. Dr. Stewart agreed. "The patients really didn’t eat more fat, compared to the typical American diet," he noted.

Indeed, the roughly 1,700 Kcal/day low-carbohydrate diet consisted of 28% of energy from carbohydrates, 29% from protein, and 39% from fat. The isocaloric low-fat diet was 49% carbohydrate, 21% protein, and 29% fat.

Dr. Stewart reported having no financial conflicts.

LOS ANGELES – A low-carbohydrate diet produced greater weight loss than did a low-fat diet and reduced systemic inflammation to a similar extent, according to results from a 6-month randomized trial.

The finding that both types of weight-loss diets produced similar reductions in inflammatory markers should help put to rest the concern that a low-carbohydrate diet’s higher fat content might have a negative impact on cardiovascular health, explained Kerry J. Stewart, Ed.D., at the annual scientific sessions of the American Heart Association.

"The concern about the low-carbohydrate diet is coming from the biomedical community. That’s why we did this study, to challenge that whole bias against this approach," explained Dr. Stewart, professor of cardiology and director of clinical research on exercise physiology at Johns Hopkins University, Baltimore.

"We’ve been told for the last 30-40 years, especially by the AHA and other groups, that high fat in the diet raises cholesterol and that all the other things that go along with that have harmful effects on the vasculature," he noted. "But we’ve previously shown no adverse effects on endothelial function or vascular stiffness, [as well as] significant improvements in blood pressure and cholesterol levels, with a low-carbohydrate diet."

Dr. Stewart reported on 60 middle-age overweight or obese patients who participated in a lifestyle intervention consisting of an exercise program plus randomization to a low-fat diet or an isocaloric low-carbohydrate diet.

From a mean baseline body weight of 97.1 kg, patients in the low-carbohydrate-diet group lost an average of 13.1 kg over 6 months, compared with 8.2 kg in the patients on the low-fat diet. From a mean baseline of 43.3%, total body fat dropped by an absolute 6.8% in the low-carb group, a significantly better result than the 4.0% decrease in the low-fat group. From a baseline mean body mass index of 34.2 kg/m², BMI improved by 4.7 kg/m² in the low-carbohydrate diet group, compared with 2.9 kg/m² with the low-fat diet.

High-sensitivity C-reactive protein levels fell by a mean of 1.8 mg/L in both groups, from 5.2 mg/L at baseline. The other markers of systemic inflammation measured in the study – levels of interleukin-6 and tumor necrosis factor-alpha – also improved to a similar degree in both study arms.

"It’s important to keep in mind that this was a weight-loss study. If someone is normal- or underweight and eats this kind of low-carbohydrate diet, I’m not exactly sure what would happen," Dr. Stewart observed. "But in the context of a weight-loss program, it seems like the weight loss is an overwhelming benefit that overcomes any possible risks from eating more fat."

One audience member who had helped run a study of an Atkins-type low-carb/high-fat diet said he and his coinvestigators found deleterious effects on arterial flow-mediated dilation over the course of a year. But Dr. Stewart was unconvinced.

"We’ve looked at that literature. It’s a real mixed bag. Some studies show just what you say, others show just the opposite," he replied. "It’s very hard to draw any conclusions from these feeding studies. We’ve done some of them ourselves and found just the opposite of what you said."

Also, as another audience member pointed out, the low-carbohydrate diet employed in this study wasn’t an Atkins-type diet that’s high in total and saturated fat. Dr. Stewart agreed. "The patients really didn’t eat more fat, compared to the typical American diet," he noted.

Indeed, the roughly 1,700 Kcal/day low-carbohydrate diet consisted of 28% of energy from carbohydrates, 29% from protein, and 39% from fat. The isocaloric low-fat diet was 49% carbohydrate, 21% protein, and 29% fat.

Dr. Stewart reported having no financial conflicts.

LOS ANGELES – A low-carbohydrate diet produced greater weight loss than did a low-fat diet and reduced systemic inflammation to a similar extent, according to results from a 6-month randomized trial.

The finding that both types of weight-loss diets produced similar reductions in inflammatory markers should help put to rest the concern that a low-carbohydrate diet’s higher fat content might have a negative impact on cardiovascular health, explained Kerry J. Stewart, Ed.D., at the annual scientific sessions of the American Heart Association.

"The concern about the low-carbohydrate diet is coming from the biomedical community. That’s why we did this study, to challenge that whole bias against this approach," explained Dr. Stewart, professor of cardiology and director of clinical research on exercise physiology at Johns Hopkins University, Baltimore.

"We’ve been told for the last 30-40 years, especially by the AHA and other groups, that high fat in the diet raises cholesterol and that all the other things that go along with that have harmful effects on the vasculature," he noted. "But we’ve previously shown no adverse effects on endothelial function or vascular stiffness, [as well as] significant improvements in blood pressure and cholesterol levels, with a low-carbohydrate diet."

Dr. Stewart reported on 60 middle-age overweight or obese patients who participated in a lifestyle intervention consisting of an exercise program plus randomization to a low-fat diet or an isocaloric low-carbohydrate diet.

From a mean baseline body weight of 97.1 kg, patients in the low-carbohydrate-diet group lost an average of 13.1 kg over 6 months, compared with 8.2 kg in the patients on the low-fat diet. From a mean baseline of 43.3%, total body fat dropped by an absolute 6.8% in the low-carb group, a significantly better result than the 4.0% decrease in the low-fat group. From a baseline mean body mass index of 34.2 kg/m², BMI improved by 4.7 kg/m² in the low-carbohydrate diet group, compared with 2.9 kg/m² with the low-fat diet.

High-sensitivity C-reactive protein levels fell by a mean of 1.8 mg/L in both groups, from 5.2 mg/L at baseline. The other markers of systemic inflammation measured in the study – levels of interleukin-6 and tumor necrosis factor-alpha – also improved to a similar degree in both study arms.

"It’s important to keep in mind that this was a weight-loss study. If someone is normal- or underweight and eats this kind of low-carbohydrate diet, I’m not exactly sure what would happen," Dr. Stewart observed. "But in the context of a weight-loss program, it seems like the weight loss is an overwhelming benefit that overcomes any possible risks from eating more fat."

One audience member who had helped run a study of an Atkins-type low-carb/high-fat diet said he and his coinvestigators found deleterious effects on arterial flow-mediated dilation over the course of a year. But Dr. Stewart was unconvinced.

"We’ve looked at that literature. It’s a real mixed bag. Some studies show just what you say, others show just the opposite," he replied. "It’s very hard to draw any conclusions from these feeding studies. We’ve done some of them ourselves and found just the opposite of what you said."

Also, as another audience member pointed out, the low-carbohydrate diet employed in this study wasn’t an Atkins-type diet that’s high in total and saturated fat. Dr. Stewart agreed. "The patients really didn’t eat more fat, compared to the typical American diet," he noted.

Indeed, the roughly 1,700 Kcal/day low-carbohydrate diet consisted of 28% of energy from carbohydrates, 29% from protein, and 39% from fat. The isocaloric low-fat diet was 49% carbohydrate, 21% protein, and 29% fat.

Dr. Stewart reported having no financial conflicts.

LOS ANGELES – Aggressive control of blood pressure, lipids, and hemoglobin A_1c in Americans with type 2 diabetes would prevent nearly 1 million fatal and nonfatal myocardial infarctions and sudden cardiac deaths over 10 years.

A less aggressive approach – one that brings those risk factors to guideline-recommended targets but no further in patients not currently at goal – would still prevent more than 600,000 coronary heart disease (CHD) events, according to the first study to estimate the population-wide impact of achieving composite control of these major risk factors in the U.S. type 2 diabetic population.

The key to achieving preventive success on this enormous scale is to attain composite risk factor control, Nathan D. Wong, Ph. D., stressed at the annual scientific sessions of the American Heart Association.

"One of the things that needs to be emphasized is we have to have a coordinated approach, where people are taking care of all of their risk factors. All too frequently, we might take care of A_1c but the blood pressure and lipids are not well controlled, or vice versa," said Dr. Wong, professor of medicine and director of the University of California, Irvine, Heart Disease Prevention Program.

"In another recent paper we did [Diab. Vasc. Dis. Res. 2012;9:146-52], we showed that less than 13% of the U.S. diabetic population is in simultaneous control of blood pressure, A_1c, and lipids, so we still have a long way to go in terms of getting our diabetic patients to goal," he added.

In the study he presented at the meeting, Dr. Wong and his coinvestigators extrapolated from weighted, nationally representative data for 2007-2008 on 384 adults with type 2 diabetes and no history of CHD or stroke, in order to create a portrait of the cardiovascular risk factor status of 9.6 million such U.S. patients. The data came from the U.S. National Health and Nutrition Examination Survey (NHANES).

Next the investigators utilized the U.K. Prospective Diabetes Study risk engine version 1.1 to estimate the group’s 10-year risk of CHD events as-is. They then examined the impact of improved control of blood pressure, HbA_1c, high-density lipoprotein, and total cholesterol by recalculating 10-year risk based upon better risk factor numbers.

The baseline 10-year risk of CHD events, defined conservatively as fatal or nonfatal acute MI or sudden death, was calculated at 23% in U.S. type 2 diabetic men and 12.1% in women. This translated to a projected 1.7 million CHD events among 9.6 million individuals over 10 years if their risk factor status remained unchanged.

However, the investigators projected that by controlling these risk factors to goal – that is, an HbA_1c of less than 7.0%, systolic blood pressure of 130 mm Hg, total cholesterol of 170 mg/dL, and HDL of 40 mg/dL in men and 50 mg/dL in women – then 32% of CHD events in men and 39% in women would be prevented. That translates to a projected 618,100 fewer major CHD events in this population. For this study, a total cholesterol of 170 mg/dL served as a proxy for an LDL cholesterol of 100 mg/dL.

Moreover, aggressive risk factor control, defined by Dr. Wong and his coworkers as a 50% reduction from baseline in total cholesterol, a 20% increase in HDL, and a 20% decrease in systolic blood pressure, combined with an absolute 2% reduction in HbA_1c, was projected to prevent 51% of CHD events in men and 58% in women with type 2 diabetes. That’s 937,320 fewer CHD events over 10 years.

Session cochair Dr. Martin K. Rutter commented, "It’s a very positive message, I think, that medical therapy has potentially such great good to do. We sometimes forget how much good we can do with our simple tools in the clinic."

Also, because the UKPDS was conducted in an era before modern aggressive risk factor reduction became common, the risk engine may actually underestimate the true value of this intensified approach in terms of preventable CHD events, said Dr. Rutter, a diabetologist at the University of Manchester (U.K.).

Dr. Wong agreed. He added that there are a couple of other reasons to think the UKPDS research engine may have undervalued the true impact of simultaneous risk factor control. For one, the investigators didn’t include the implications of smoking cessation in their calculations.

Also, NHANES did not record whether participants had atrial fibrillation, so Dr. Wong and his coworkers were forced into making risk calculations based on the false assumption that atrial fibrillation was nonexistent in the type 2 diabetic population. In reality, of course, the presence of this common arrhythmia in type 2 diabetic individuals further increases their cardiovascular risk, and thus the benefits of risk factor reduction would become magnified.

This analysis was funded by Bristol-Myers Squibb. Dr. Wong reported receiving a research grant from that company to conduct the study. In addition, he serves as a consultant to Merck, LipoScience, and Reengineering Healthcare.

b.jancin@elsevier.com

LOS ANGELES – Aggressive control of blood pressure, lipids, and hemoglobin A_1c in Americans with type 2 diabetes would prevent nearly 1 million fatal and nonfatal myocardial infarctions and sudden cardiac deaths over 10 years.

A less aggressive approach – one that brings those risk factors to guideline-recommended targets but no further in patients not currently at goal – would still prevent more than 600,000 coronary heart disease (CHD) events, according to the first study to estimate the population-wide impact of achieving composite control of these major risk factors in the U.S. type 2 diabetic population.

The key to achieving preventive success on this enormous scale is to attain composite risk factor control, Nathan D. Wong, Ph. D., stressed at the annual scientific sessions of the American Heart Association.

"One of the things that needs to be emphasized is we have to have a coordinated approach, where people are taking care of all of their risk factors. All too frequently, we might take care of A_1c but the blood pressure and lipids are not well controlled, or vice versa," said Dr. Wong, professor of medicine and director of the University of California, Irvine, Heart Disease Prevention Program.

"In another recent paper we did [Diab. Vasc. Dis. Res. 2012;9:146-52], we showed that less than 13% of the U.S. diabetic population is in simultaneous control of blood pressure, A_1c, and lipids, so we still have a long way to go in terms of getting our diabetic patients to goal," he added.

In the study he presented at the meeting, Dr. Wong and his coinvestigators extrapolated from weighted, nationally representative data for 2007-2008 on 384 adults with type 2 diabetes and no history of CHD or stroke, in order to create a portrait of the cardiovascular risk factor status of 9.6 million such U.S. patients. The data came from the U.S. National Health and Nutrition Examination Survey (NHANES).

Next the investigators utilized the U.K. Prospective Diabetes Study risk engine version 1.1 to estimate the group’s 10-year risk of CHD events as-is. They then examined the impact of improved control of blood pressure, HbA_1c, high-density lipoprotein, and total cholesterol by recalculating 10-year risk based upon better risk factor numbers.

The baseline 10-year risk of CHD events, defined conservatively as fatal or nonfatal acute MI or sudden death, was calculated at 23% in U.S. type 2 diabetic men and 12.1% in women. This translated to a projected 1.7 million CHD events among 9.6 million individuals over 10 years if their risk factor status remained unchanged.

However, the investigators projected that by controlling these risk factors to goal – that is, an HbA_1c of less than 7.0%, systolic blood pressure of 130 mm Hg, total cholesterol of 170 mg/dL, and HDL of 40 mg/dL in men and 50 mg/dL in women – then 32% of CHD events in men and 39% in women would be prevented. That translates to a projected 618,100 fewer major CHD events in this population. For this study, a total cholesterol of 170 mg/dL served as a proxy for an LDL cholesterol of 100 mg/dL.

Moreover, aggressive risk factor control, defined by Dr. Wong and his coworkers as a 50% reduction from baseline in total cholesterol, a 20% increase in HDL, and a 20% decrease in systolic blood pressure, combined with an absolute 2% reduction in HbA_1c, was projected to prevent 51% of CHD events in men and 58% in women with type 2 diabetes. That’s 937,320 fewer CHD events over 10 years.

Session cochair Dr. Martin K. Rutter commented, "It’s a very positive message, I think, that medical therapy has potentially such great good to do. We sometimes forget how much good we can do with our simple tools in the clinic."

Also, because the UKPDS was conducted in an era before modern aggressive risk factor reduction became common, the risk engine may actually underestimate the true value of this intensified approach in terms of preventable CHD events, said Dr. Rutter, a diabetologist at the University of Manchester (U.K.).

Dr. Wong agreed. He added that there are a couple of other reasons to think the UKPDS research engine may have undervalued the true impact of simultaneous risk factor control. For one, the investigators didn’t include the implications of smoking cessation in their calculations.

Also, NHANES did not record whether participants had atrial fibrillation, so Dr. Wong and his coworkers were forced into making risk calculations based on the false assumption that atrial fibrillation was nonexistent in the type 2 diabetic population. In reality, of course, the presence of this common arrhythmia in type 2 diabetic individuals further increases their cardiovascular risk, and thus the benefits of risk factor reduction would become magnified.

This analysis was funded by Bristol-Myers Squibb. Dr. Wong reported receiving a research grant from that company to conduct the study. In addition, he serves as a consultant to Merck, LipoScience, and Reengineering Healthcare.

b.jancin@elsevier.com

LOS ANGELES – Aggressive control of blood pressure, lipids, and hemoglobin A_1c in Americans with type 2 diabetes would prevent nearly 1 million fatal and nonfatal myocardial infarctions and sudden cardiac deaths over 10 years.

A less aggressive approach – one that brings those risk factors to guideline-recommended targets but no further in patients not currently at goal – would still prevent more than 600,000 coronary heart disease (CHD) events, according to the first study to estimate the population-wide impact of achieving composite control of these major risk factors in the U.S. type 2 diabetic population.

The key to achieving preventive success on this enormous scale is to attain composite risk factor control, Nathan D. Wong, Ph. D., stressed at the annual scientific sessions of the American Heart Association.

"One of the things that needs to be emphasized is we have to have a coordinated approach, where people are taking care of all of their risk factors. All too frequently, we might take care of A_1c but the blood pressure and lipids are not well controlled, or vice versa," said Dr. Wong, professor of medicine and director of the University of California, Irvine, Heart Disease Prevention Program.

"In another recent paper we did [Diab. Vasc. Dis. Res. 2012;9:146-52], we showed that less than 13% of the U.S. diabetic population is in simultaneous control of blood pressure, A_1c, and lipids, so we still have a long way to go in terms of getting our diabetic patients to goal," he added.

In the study he presented at the meeting, Dr. Wong and his coinvestigators extrapolated from weighted, nationally representative data for 2007-2008 on 384 adults with type 2 diabetes and no history of CHD or stroke, in order to create a portrait of the cardiovascular risk factor status of 9.6 million such U.S. patients. The data came from the U.S. National Health and Nutrition Examination Survey (NHANES).

Next the investigators utilized the U.K. Prospective Diabetes Study risk engine version 1.1 to estimate the group’s 10-year risk of CHD events as-is. They then examined the impact of improved control of blood pressure, HbA_1c, high-density lipoprotein, and total cholesterol by recalculating 10-year risk based upon better risk factor numbers.

The baseline 10-year risk of CHD events, defined conservatively as fatal or nonfatal acute MI or sudden death, was calculated at 23% in U.S. type 2 diabetic men and 12.1% in women. This translated to a projected 1.7 million CHD events among 9.6 million individuals over 10 years if their risk factor status remained unchanged.

However, the investigators projected that by controlling these risk factors to goal – that is, an HbA_1c of less than 7.0%, systolic blood pressure of 130 mm Hg, total cholesterol of 170 mg/dL, and HDL of 40 mg/dL in men and 50 mg/dL in women – then 32% of CHD events in men and 39% in women would be prevented. That translates to a projected 618,100 fewer major CHD events in this population. For this study, a total cholesterol of 170 mg/dL served as a proxy for an LDL cholesterol of 100 mg/dL.

Moreover, aggressive risk factor control, defined by Dr. Wong and his coworkers as a 50% reduction from baseline in total cholesterol, a 20% increase in HDL, and a 20% decrease in systolic blood pressure, combined with an absolute 2% reduction in HbA_1c, was projected to prevent 51% of CHD events in men and 58% in women with type 2 diabetes. That’s 937,320 fewer CHD events over 10 years.

Session cochair Dr. Martin K. Rutter commented, "It’s a very positive message, I think, that medical therapy has potentially such great good to do. We sometimes forget how much good we can do with our simple tools in the clinic."

Also, because the UKPDS was conducted in an era before modern aggressive risk factor reduction became common, the risk engine may actually underestimate the true value of this intensified approach in terms of preventable CHD events, said Dr. Rutter, a diabetologist at the University of Manchester (U.K.).

Dr. Wong agreed. He added that there are a couple of other reasons to think the UKPDS research engine may have undervalued the true impact of simultaneous risk factor control. For one, the investigators didn’t include the implications of smoking cessation in their calculations.

Also, NHANES did not record whether participants had atrial fibrillation, so Dr. Wong and his coworkers were forced into making risk calculations based on the false assumption that atrial fibrillation was nonexistent in the type 2 diabetic population. In reality, of course, the presence of this common arrhythmia in type 2 diabetic individuals further increases their cardiovascular risk, and thus the benefits of risk factor reduction would become magnified.

This analysis was funded by Bristol-Myers Squibb. Dr. Wong reported receiving a research grant from that company to conduct the study. In addition, he serves as a consultant to Merck, LipoScience, and Reengineering Healthcare.

b.jancin@elsevier.com

LOS ANGELES – If you look old for your chronologic age, chances are your coronary arteries are undergoing accelerated biologic aging, too, judging from findings in a new report from the landmark Copenhagen City Heart Study.

Several specific skin signs of aging serve as significant predictors of increased risk for ischemic heart disease independent of chronologic age and the standard cardiovascular risk factors, Dr. Anne Tybaerg-Hansen reported at the annual scientific sessions of the American Heart Association.

Bruce Jancin/IMNG Medical Media

"I think this is pretty useful information clinically. If you look at your patients right, it’ll give you an idea of their cardiovascular health independent of their chronologic age. And when you see these traits that are not dependent on the well-known cardiovascular risk factors, then you should perhaps treat them more diligently, because their 10-year risk is higher than in individuals in the same age groups who do not have these aging signs," explained Dr. Tybaerg-Hansen, professor of clinical biochemistry at the University of Copenhagen.

When nearly 11,000 participants in the prospective Copenhagen City Heart Study had their first physical examination back in 1976-1978, investigators blinded as to subjects’ health status systematically recorded visible signs of aging using prespecified criteria. Since then, during a mean follow-up of 35 years, there have been 3,401 ischemic heart disease events, including 1,708 acute MIs, in these subjects.

In a multivariate analysis extensively adjusted for potential confounders, several classic signs of aging proved unrelated to the risk of future ischemic heart disease. Neither wrinkles, grey hair, nor arcus corneae – that is, cholesterol deposits in the eye – were independently related to risk. That implies these features are fully accounted for by chronologic age and conventional cardiovascular risk factors.

However, four aging signs remained independent predictors of increased risk after controlling for age, gender, all the standard cardiovascular risk factors, socioeconomic status, body mass index, and physical activity. Xanthelasma – yellowish deposits of cholesterol around the eyelids – was associated with a 35% increased risk of MI during follow-up. An earlobe crease was associated with a significant 11% increased risk. Crown top baldness carried a 40% increase in relative risk, while frontoparietal baldness was associated with a 14% greater risk.

These two forms of baldness were significant predictors in men only. Crown top and frontoparietal baldness also were linked to increased MI risk in women, but this association didn’t achieve statistical significance because so few women experience these aging signs.

The more of the four aging signs present at baseline, the greater the risk of subsequent acute MI. Nine percent of subjects had three or all four aging signs; their risk of acute MI was 60% greater than in individuals with none of the aging signs in the adjusted analysis. Those with one or two aging signs had increased risks of roughly 20% and 35%, respectively.

This stepwise increase in risk held true across all 10-year age groups. Among 70- to 79-year-old men, for example, those with three or four of the aging signs had a 44% absolute 10-year risk of ischemic heart disease, while those with none of the signs had a 32% risk.

Asked to speculate about the mechanisms underlying the association between the aging signs and ischemic heart disease, Dr. Tybaerg-Hansen was quick to note that "there are no scientific data at all" for guidance. That being said, high free-testosterone levels are associated with male-pattern baldness, and some studies have reported a link between free testosterone and ischemic heart disease. Also, Dr. Tybaerg-Hansen and her coworkers recently demonstrated that the increased risk of ischemic heart disease associated with xanthelasma cannot be explained by serum cholesterol or triglyceride levels (BMJ 2011;343:d5497).

Bruce Jancin/IMNG Medical Media

"So there must be something else, probably something in the connective tissue, which makes some people more prone to accumulate cholesterol. Connective tissue could also be involved in the earlobe crease. But there is as yet no hard evidence for this," she said.

Session chair Dr. Kathy Magliato, a cardiothoracic surgeon and director of women’s cardiac services at St. John’s Health Center in Los Angeles, said that the new Copenhagen City Heart Study findings confirm her own anecdotal experience.

"The majority of people who come to me because they’ve missed out on the benefits of prevention and now need heart surgery look old for their age. It’s reassuring to know now that I’m not just imagining that. The older they look, the worse their heart disease," she said.

"This study reinforces the fact that we have to look at our patients," Dr. Magliato continued. "I think doctors are sometimes so rushed to put on a blood pressure cuff and get a stethoscope on the chest that we forget to just step back and look at these visible signs of aging."

Dr. Tybaerg-Hansen reported having no financial conflicts.

b.jancin@elsevier.com

LOS ANGELES – If you look old for your chronologic age, chances are your coronary arteries are undergoing accelerated biologic aging, too, judging from findings in a new report from the landmark Copenhagen City Heart Study.

Several specific skin signs of aging serve as significant predictors of increased risk for ischemic heart disease independent of chronologic age and the standard cardiovascular risk factors, Dr. Anne Tybaerg-Hansen reported at the annual scientific sessions of the American Heart Association.

Bruce Jancin/IMNG Medical Media

"I think this is pretty useful information clinically. If you look at your patients right, it’ll give you an idea of their cardiovascular health independent of their chronologic age. And when you see these traits that are not dependent on the well-known cardiovascular risk factors, then you should perhaps treat them more diligently, because their 10-year risk is higher than in individuals in the same age groups who do not have these aging signs," explained Dr. Tybaerg-Hansen, professor of clinical biochemistry at the University of Copenhagen.

When nearly 11,000 participants in the prospective Copenhagen City Heart Study had their first physical examination back in 1976-1978, investigators blinded as to subjects’ health status systematically recorded visible signs of aging using prespecified criteria. Since then, during a mean follow-up of 35 years, there have been 3,401 ischemic heart disease events, including 1,708 acute MIs, in these subjects.

In a multivariate analysis extensively adjusted for potential confounders, several classic signs of aging proved unrelated to the risk of future ischemic heart disease. Neither wrinkles, grey hair, nor arcus corneae – that is, cholesterol deposits in the eye – were independently related to risk. That implies these features are fully accounted for by chronologic age and conventional cardiovascular risk factors.

However, four aging signs remained independent predictors of increased risk after controlling for age, gender, all the standard cardiovascular risk factors, socioeconomic status, body mass index, and physical activity. Xanthelasma – yellowish deposits of cholesterol around the eyelids – was associated with a 35% increased risk of MI during follow-up. An earlobe crease was associated with a significant 11% increased risk. Crown top baldness carried a 40% increase in relative risk, while frontoparietal baldness was associated with a 14% greater risk.

These two forms of baldness were significant predictors in men only. Crown top and frontoparietal baldness also were linked to increased MI risk in women, but this association didn’t achieve statistical significance because so few women experience these aging signs.

The more of the four aging signs present at baseline, the greater the risk of subsequent acute MI. Nine percent of subjects had three or all four aging signs; their risk of acute MI was 60% greater than in individuals with none of the aging signs in the adjusted analysis. Those with one or two aging signs had increased risks of roughly 20% and 35%, respectively.

This stepwise increase in risk held true across all 10-year age groups. Among 70- to 79-year-old men, for example, those with three or four of the aging signs had a 44% absolute 10-year risk of ischemic heart disease, while those with none of the signs had a 32% risk.

Asked to speculate about the mechanisms underlying the association between the aging signs and ischemic heart disease, Dr. Tybaerg-Hansen was quick to note that "there are no scientific data at all" for guidance. That being said, high free-testosterone levels are associated with male-pattern baldness, and some studies have reported a link between free testosterone and ischemic heart disease. Also, Dr. Tybaerg-Hansen and her coworkers recently demonstrated that the increased risk of ischemic heart disease associated with xanthelasma cannot be explained by serum cholesterol or triglyceride levels (BMJ 2011;343:d5497).

Bruce Jancin/IMNG Medical Media

"So there must be something else, probably something in the connective tissue, which makes some people more prone to accumulate cholesterol. Connective tissue could also be involved in the earlobe crease. But there is as yet no hard evidence for this," she said.

Session chair Dr. Kathy Magliato, a cardiothoracic surgeon and director of women’s cardiac services at St. John’s Health Center in Los Angeles, said that the new Copenhagen City Heart Study findings confirm her own anecdotal experience.

"The majority of people who come to me because they’ve missed out on the benefits of prevention and now need heart surgery look old for their age. It’s reassuring to know now that I’m not just imagining that. The older they look, the worse their heart disease," she said.

"This study reinforces the fact that we have to look at our patients," Dr. Magliato continued. "I think doctors are sometimes so rushed to put on a blood pressure cuff and get a stethoscope on the chest that we forget to just step back and look at these visible signs of aging."

Dr. Tybaerg-Hansen reported having no financial conflicts.

b.jancin@elsevier.com

LOS ANGELES – If you look old for your chronologic age, chances are your coronary arteries are undergoing accelerated biologic aging, too, judging from findings in a new report from the landmark Copenhagen City Heart Study.

Several specific skin signs of aging serve as significant predictors of increased risk for ischemic heart disease independent of chronologic age and the standard cardiovascular risk factors, Dr. Anne Tybaerg-Hansen reported at the annual scientific sessions of the American Heart Association.

Bruce Jancin/IMNG Medical Media

"I think this is pretty useful information clinically. If you look at your patients right, it’ll give you an idea of their cardiovascular health independent of their chronologic age. And when you see these traits that are not dependent on the well-known cardiovascular risk factors, then you should perhaps treat them more diligently, because their 10-year risk is higher than in individuals in the same age groups who do not have these aging signs," explained Dr. Tybaerg-Hansen, professor of clinical biochemistry at the University of Copenhagen.

When nearly 11,000 participants in the prospective Copenhagen City Heart Study had their first physical examination back in 1976-1978, investigators blinded as to subjects’ health status systematically recorded visible signs of aging using prespecified criteria. Since then, during a mean follow-up of 35 years, there have been 3,401 ischemic heart disease events, including 1,708 acute MIs, in these subjects.

In a multivariate analysis extensively adjusted for potential confounders, several classic signs of aging proved unrelated to the risk of future ischemic heart disease. Neither wrinkles, grey hair, nor arcus corneae – that is, cholesterol deposits in the eye – were independently related to risk. That implies these features are fully accounted for by chronologic age and conventional cardiovascular risk factors.

However, four aging signs remained independent predictors of increased risk after controlling for age, gender, all the standard cardiovascular risk factors, socioeconomic status, body mass index, and physical activity. Xanthelasma – yellowish deposits of cholesterol around the eyelids – was associated with a 35% increased risk of MI during follow-up. An earlobe crease was associated with a significant 11% increased risk. Crown top baldness carried a 40% increase in relative risk, while frontoparietal baldness was associated with a 14% greater risk.

These two forms of baldness were significant predictors in men only. Crown top and frontoparietal baldness also were linked to increased MI risk in women, but this association didn’t achieve statistical significance because so few women experience these aging signs.

The more of the four aging signs present at baseline, the greater the risk of subsequent acute MI. Nine percent of subjects had three or all four aging signs; their risk of acute MI was 60% greater than in individuals with none of the aging signs in the adjusted analysis. Those with one or two aging signs had increased risks of roughly 20% and 35%, respectively.

This stepwise increase in risk held true across all 10-year age groups. Among 70- to 79-year-old men, for example, those with three or four of the aging signs had a 44% absolute 10-year risk of ischemic heart disease, while those with none of the signs had a 32% risk.

Asked to speculate about the mechanisms underlying the association between the aging signs and ischemic heart disease, Dr. Tybaerg-Hansen was quick to note that "there are no scientific data at all" for guidance. That being said, high free-testosterone levels are associated with male-pattern baldness, and some studies have reported a link between free testosterone and ischemic heart disease. Also, Dr. Tybaerg-Hansen and her coworkers recently demonstrated that the increased risk of ischemic heart disease associated with xanthelasma cannot be explained by serum cholesterol or triglyceride levels (BMJ 2011;343:d5497).

Bruce Jancin/IMNG Medical Media

"So there must be something else, probably something in the connective tissue, which makes some people more prone to accumulate cholesterol. Connective tissue could also be involved in the earlobe crease. But there is as yet no hard evidence for this," she said.

Session chair Dr. Kathy Magliato, a cardiothoracic surgeon and director of women’s cardiac services at St. John’s Health Center in Los Angeles, said that the new Copenhagen City Heart Study findings confirm her own anecdotal experience.

"The majority of people who come to me because they’ve missed out on the benefits of prevention and now need heart surgery look old for their age. It’s reassuring to know now that I’m not just imagining that. The older they look, the worse their heart disease," she said.

"This study reinforces the fact that we have to look at our patients," Dr. Magliato continued. "I think doctors are sometimes so rushed to put on a blood pressure cuff and get a stethoscope on the chest that we forget to just step back and look at these visible signs of aging."

Dr. Tybaerg-Hansen reported having no financial conflicts.

b.jancin@elsevier.com

A novel proprietary combination of aspirin and immediate-release omeprazole in a coordinated-delivery tablet resulted in markedly fewer gastric ulcers and treatment discontinuations than conventional enteric-coated aspirin in two pivotal phase III clinical trials reported at the annual scientific sessions of the American Heart Association.

The two double-blind, 6-month, multicenter, randomized phase III studies included 1,049 patients who had coronary heart disease and were taking aspirin for secondary cardiovascular prevention. Based upon the highly favorable results reported by Dr. David L. Whellan at the meeting as well as other evidence, the studies’ sponsor, Pozen, will seek regulatory approval of the coordinated-delivery product with an indication for use in secondary prevention of cardiovascular events in the roughly 15% of patients at risk for aspirin-induced upper-GI adverse events.

Study participants were randomized to once-daily conventional enteric-coated aspirin at 325 mg or to the investigational tablet, known for now as PA32540. The primary endpoint – the 6-month rate of endoscopically confirmed gastric ulcers – occurred in 3.8% of the PA32540 group, compared with 8.7% of controls, in one 524-patient study and in 2.7% of the PA32540 group, versus 8.5% of controls, in the 525-patient second study. This corresponds to relative risk reductions of 56% and 68%, respectively, according to Dr. Whellan of Thomas Jefferson University, Philadelphia.

A key secondary endpoint was the 6-month treatment discontinuation rate as a result of dyspepsia, erosive gastritis, and other upper-GI adverse events. The combined rate in the two trials was 1.5% in the PA32540 group and 8.2% in patients on enteric-coated aspirin, for an 82% relative risk reduction.

The rate of discontinuation for any adverse events was 6.7% with PA32540 and 11.2% in controls. Since patient adherence to aspirin therapy saves lives, these are clinically important outcomes, he noted.

The rate of acute MI and other major adverse cardiovascular events was 1.7% in the PA32540 group and 2.5% in controls, a nonsignificant difference. The study wasn’t of sufficient size or duration to provide definitive evidence regarding this endpoint.

PA32540 is a once-daily tablet containing 40 mg of immediate-release omeprazole layered around 325 mg of pH-sensitive aspirin. Pozen has announced that it is currently seeking strategic partners to help market the novel product on a wide scale at an affordable cost once PA32540 receives regulatory approval.

Dr. Whellan is a consultant to Pozen.

A novel proprietary combination of aspirin and immediate-release omeprazole in a coordinated-delivery tablet resulted in markedly fewer gastric ulcers and treatment discontinuations than conventional enteric-coated aspirin in two pivotal phase III clinical trials reported at the annual scientific sessions of the American Heart Association.

The two double-blind, 6-month, multicenter, randomized phase III studies included 1,049 patients who had coronary heart disease and were taking aspirin for secondary cardiovascular prevention. Based upon the highly favorable results reported by Dr. David L. Whellan at the meeting as well as other evidence, the studies’ sponsor, Pozen, will seek regulatory approval of the coordinated-delivery product with an indication for use in secondary prevention of cardiovascular events in the roughly 15% of patients at risk for aspirin-induced upper-GI adverse events.

Study participants were randomized to once-daily conventional enteric-coated aspirin at 325 mg or to the investigational tablet, known for now as PA32540. The primary endpoint – the 6-month rate of endoscopically confirmed gastric ulcers – occurred in 3.8% of the PA32540 group, compared with 8.7% of controls, in one 524-patient study and in 2.7% of the PA32540 group, versus 8.5% of controls, in the 525-patient second study. This corresponds to relative risk reductions of 56% and 68%, respectively, according to Dr. Whellan of Thomas Jefferson University, Philadelphia.

A key secondary endpoint was the 6-month treatment discontinuation rate as a result of dyspepsia, erosive gastritis, and other upper-GI adverse events. The combined rate in the two trials was 1.5% in the PA32540 group and 8.2% in patients on enteric-coated aspirin, for an 82% relative risk reduction.

The rate of discontinuation for any adverse events was 6.7% with PA32540 and 11.2% in controls. Since patient adherence to aspirin therapy saves lives, these are clinically important outcomes, he noted.

The rate of acute MI and other major adverse cardiovascular events was 1.7% in the PA32540 group and 2.5% in controls, a nonsignificant difference. The study wasn’t of sufficient size or duration to provide definitive evidence regarding this endpoint.

PA32540 is a once-daily tablet containing 40 mg of immediate-release omeprazole layered around 325 mg of pH-sensitive aspirin. Pozen has announced that it is currently seeking strategic partners to help market the novel product on a wide scale at an affordable cost once PA32540 receives regulatory approval.

Dr. Whellan is a consultant to Pozen.

A novel proprietary combination of aspirin and immediate-release omeprazole in a coordinated-delivery tablet resulted in markedly fewer gastric ulcers and treatment discontinuations than conventional enteric-coated aspirin in two pivotal phase III clinical trials reported at the annual scientific sessions of the American Heart Association.

The two double-blind, 6-month, multicenter, randomized phase III studies included 1,049 patients who had coronary heart disease and were taking aspirin for secondary cardiovascular prevention. Based upon the highly favorable results reported by Dr. David L. Whellan at the meeting as well as other evidence, the studies’ sponsor, Pozen, will seek regulatory approval of the coordinated-delivery product with an indication for use in secondary prevention of cardiovascular events in the roughly 15% of patients at risk for aspirin-induced upper-GI adverse events.

Study participants were randomized to once-daily conventional enteric-coated aspirin at 325 mg or to the investigational tablet, known for now as PA32540. The primary endpoint – the 6-month rate of endoscopically confirmed gastric ulcers – occurred in 3.8% of the PA32540 group, compared with 8.7% of controls, in one 524-patient study and in 2.7% of the PA32540 group, versus 8.5% of controls, in the 525-patient second study. This corresponds to relative risk reductions of 56% and 68%, respectively, according to Dr. Whellan of Thomas Jefferson University, Philadelphia.

A key secondary endpoint was the 6-month treatment discontinuation rate as a result of dyspepsia, erosive gastritis, and other upper-GI adverse events. The combined rate in the two trials was 1.5% in the PA32540 group and 8.2% in patients on enteric-coated aspirin, for an 82% relative risk reduction.

The rate of discontinuation for any adverse events was 6.7% with PA32540 and 11.2% in controls. Since patient adherence to aspirin therapy saves lives, these are clinically important outcomes, he noted.

The rate of acute MI and other major adverse cardiovascular events was 1.7% in the PA32540 group and 2.5% in controls, a nonsignificant difference. The study wasn’t of sufficient size or duration to provide definitive evidence regarding this endpoint.

PA32540 is a once-daily tablet containing 40 mg of immediate-release omeprazole layered around 325 mg of pH-sensitive aspirin. Pozen has announced that it is currently seeking strategic partners to help market the novel product on a wide scale at an affordable cost once PA32540 receives regulatory approval.

Dr. Whellan is a consultant to Pozen.

The combination of intravenous immunoglobulin, aspirin, and prednisolone appears to be the most effective form of rescue therapy for patients with acute Kawasaki disease who don’t respond to initial IVIG plus aspirin, according to a large Japanese observational study.

Dr. Tohru Kobayashi reported on 375 consecutive patients resistant to initial standard therapy with IVIG plus aspirin. In nonrandomized fashion, 141 received another course of IVIG as first-line rescue therapy, 80 got prednisolone, and 154 were put on IVIG plus prednisolone. All patients also received aspirin.

The rescue therapy failure rate was significantly lower in patients who got IVIG combined with prednisolone, 12.3%, compared with 38.3% with IVIG alone and 30% with prednisolone, according to Dr. Kobayashi of Gunma University in Maebashi, Japan.

Moreover, the prevalence of coronary artery aneurysms at 1 month was 6.5% with combination rescue therapy, significantly lower than the 14.9% figure with rescue IVIG or the 16.3% prevalence with prednisolone, Dr. Kobayashi said at the annual scientific sessions of the American Heart Association.

Compared with the rescue IVIG group, patients who received rescue IVIG plus prednisolone had an adjusted 84% lower risk of failing to respond to initial rescue therapy. They were also 61% less likely to have a coronary artery aneurysm at 1 month.

This study was funded by the Japanese Ministry of Health, Labor, and Comprehensive Research on Practical Application of Medical Technology. Dr. Kobayashi reported having no financial conflicts.

The combination of intravenous immunoglobulin, aspirin, and prednisolone appears to be the most effective form of rescue therapy for patients with acute Kawasaki disease who don’t respond to initial IVIG plus aspirin, according to a large Japanese observational study.

Dr. Tohru Kobayashi reported on 375 consecutive patients resistant to initial standard therapy with IVIG plus aspirin. In nonrandomized fashion, 141 received another course of IVIG as first-line rescue therapy, 80 got prednisolone, and 154 were put on IVIG plus prednisolone. All patients also received aspirin.

The rescue therapy failure rate was significantly lower in patients who got IVIG combined with prednisolone, 12.3%, compared with 38.3% with IVIG alone and 30% with prednisolone, according to Dr. Kobayashi of Gunma University in Maebashi, Japan.

Moreover, the prevalence of coronary artery aneurysms at 1 month was 6.5% with combination rescue therapy, significantly lower than the 14.9% figure with rescue IVIG or the 16.3% prevalence with prednisolone, Dr. Kobayashi said at the annual scientific sessions of the American Heart Association.

Compared with the rescue IVIG group, patients who received rescue IVIG plus prednisolone had an adjusted 84% lower risk of failing to respond to initial rescue therapy. They were also 61% less likely to have a coronary artery aneurysm at 1 month.

This study was funded by the Japanese Ministry of Health, Labor, and Comprehensive Research on Practical Application of Medical Technology. Dr. Kobayashi reported having no financial conflicts.

The combination of intravenous immunoglobulin, aspirin, and prednisolone appears to be the most effective form of rescue therapy for patients with acute Kawasaki disease who don’t respond to initial IVIG plus aspirin, according to a large Japanese observational study.

Dr. Tohru Kobayashi reported on 375 consecutive patients resistant to initial standard therapy with IVIG plus aspirin. In nonrandomized fashion, 141 received another course of IVIG as first-line rescue therapy, 80 got prednisolone, and 154 were put on IVIG plus prednisolone. All patients also received aspirin.

The rescue therapy failure rate was significantly lower in patients who got IVIG combined with prednisolone, 12.3%, compared with 38.3% with IVIG alone and 30% with prednisolone, according to Dr. Kobayashi of Gunma University in Maebashi, Japan.

Moreover, the prevalence of coronary artery aneurysms at 1 month was 6.5% with combination rescue therapy, significantly lower than the 14.9% figure with rescue IVIG or the 16.3% prevalence with prednisolone, Dr. Kobayashi said at the annual scientific sessions of the American Heart Association.

Compared with the rescue IVIG group, patients who received rescue IVIG plus prednisolone had an adjusted 84% lower risk of failing to respond to initial rescue therapy. They were also 61% less likely to have a coronary artery aneurysm at 1 month.

This study was funded by the Japanese Ministry of Health, Labor, and Comprehensive Research on Practical Application of Medical Technology. Dr. Kobayashi reported having no financial conflicts.

LOS ANGELES – The use of selective serotonin reuptake inhibitors in treating combat posttraumatic stress disorder in middle-aged veterans was associated with sharply reduced cardiovascular mortality in a large observational study, according to Dr. Naser Ahmadi of the VA Greater Los Angeles Healthcare System.

Treatment with a selective serotonin reuptake inhibitor also appeared to protect against development of metabolic syndrome in this patient population, he added at the annual scientific sessions of the American Heart Association.

Dr. Ahmadi reported on 1,142 veterans with combat-induced PTSD, 433 of whom had received SSRI therapy for the disorder. Fifty-three percent of subjects met criteria for metabolic syndrome.

During a median 5 years of follow-up through the Veterans Affairs system’s electronic medical record system, the cardiovascular mortality was 21% in patients with PTSD and metabolic syndrome, compared with 14% in those without metabolic syndrome. Thus, comorbid metabolic syndrome in patients with combat PTSD was associated with a 68% increase in the risk of cardiovascular mortality.

The prevalence of metabolic syndrome was 32% among SSRI recipients, compared with 45% in those whose PTSD was not treated SSRIs. After adjusting for age, gender, and conventional cardiovascular risk factors in a multivariate analysis, the relative risk of metabolic syndrome in patients with PTSD was 71% lower with SSRI therapy than without it.

Moreover, the adjusted risk of cardiovascular mortality over the course of a median 5 years of follow-up in this hypothesis-generating observational study was 36% lower in SSRI-treated patients with PTSD and metabolic syndrome than in those not on an SSRI, and 64% lower in SSRI-treated patients with PTSD without metabolic syndrome.

This study received funding from the American Heart Association. Dr. Ahmadi reported having no financial conflicts.

b.jancin@elsevier.com

LOS ANGELES – The use of selective serotonin reuptake inhibitors in treating combat posttraumatic stress disorder in middle-aged veterans was associated with sharply reduced cardiovascular mortality in a large observational study, according to Dr. Naser Ahmadi of the VA Greater Los Angeles Healthcare System.

Treatment with a selective serotonin reuptake inhibitor also appeared to protect against development of metabolic syndrome in this patient population, he added at the annual scientific sessions of the American Heart Association.

Dr. Ahmadi reported on 1,142 veterans with combat-induced PTSD, 433 of whom had received SSRI therapy for the disorder. Fifty-three percent of subjects met criteria for metabolic syndrome.

During a median 5 years of follow-up through the Veterans Affairs system’s electronic medical record system, the cardiovascular mortality was 21% in patients with PTSD and metabolic syndrome, compared with 14% in those without metabolic syndrome. Thus, comorbid metabolic syndrome in patients with combat PTSD was associated with a 68% increase in the risk of cardiovascular mortality.

The prevalence of metabolic syndrome was 32% among SSRI recipients, compared with 45% in those whose PTSD was not treated SSRIs. After adjusting for age, gender, and conventional cardiovascular risk factors in a multivariate analysis, the relative risk of metabolic syndrome in patients with PTSD was 71% lower with SSRI therapy than without it.

Moreover, the adjusted risk of cardiovascular mortality over the course of a median 5 years of follow-up in this hypothesis-generating observational study was 36% lower in SSRI-treated patients with PTSD and metabolic syndrome than in those not on an SSRI, and 64% lower in SSRI-treated patients with PTSD without metabolic syndrome.

This study received funding from the American Heart Association. Dr. Ahmadi reported having no financial conflicts.

b.jancin@elsevier.com

LOS ANGELES – The use of selective serotonin reuptake inhibitors in treating combat posttraumatic stress disorder in middle-aged veterans was associated with sharply reduced cardiovascular mortality in a large observational study, according to Dr. Naser Ahmadi of the VA Greater Los Angeles Healthcare System.

Treatment with a selective serotonin reuptake inhibitor also appeared to protect against development of metabolic syndrome in this patient population, he added at the annual scientific sessions of the American Heart Association.

Dr. Ahmadi reported on 1,142 veterans with combat-induced PTSD, 433 of whom had received SSRI therapy for the disorder. Fifty-three percent of subjects met criteria for metabolic syndrome.

During a median 5 years of follow-up through the Veterans Affairs system’s electronic medical record system, the cardiovascular mortality was 21% in patients with PTSD and metabolic syndrome, compared with 14% in those without metabolic syndrome. Thus, comorbid metabolic syndrome in patients with combat PTSD was associated with a 68% increase in the risk of cardiovascular mortality.

The prevalence of metabolic syndrome was 32% among SSRI recipients, compared with 45% in those whose PTSD was not treated SSRIs. After adjusting for age, gender, and conventional cardiovascular risk factors in a multivariate analysis, the relative risk of metabolic syndrome in patients with PTSD was 71% lower with SSRI therapy than without it.

Moreover, the adjusted risk of cardiovascular mortality over the course of a median 5 years of follow-up in this hypothesis-generating observational study was 36% lower in SSRI-treated patients with PTSD and metabolic syndrome than in those not on an SSRI, and 64% lower in SSRI-treated patients with PTSD without metabolic syndrome.

This study received funding from the American Heart Association. Dr. Ahmadi reported having no financial conflicts.

b.jancin@elsevier.com