ESC Congress 2011

PARIS – In patients with a first recurrence of pericarditis, adding low-dose colchicine to standard therapy halved the risk of subsequent episodes of pericarditis.

Among 120 patients with a first recurrence of pericarditis in the Study of Colchicine to Treat and Prevent Recurrent Pericarditis (CORP) trial, the rate at 18 months of another recurrence was 24% with colchicine and standard therapy and 55% with placebo and standard therapy (P value less than .001).

The relative risk reduction associated with adjuvant colchicine was 56% and the number needed to treat to prevent one recurrence was three, Dr. Massimo Imazio reported at the annual congress of the European Society of Cardiology.

Colchicine (Colcrys) has been used for years to treat gout, and is the first drug to be shown in a double-blind, randomized placebo-controlled trial to prevent recurrent pericarditis.

"Following an initial episode of recurrent pericarditis, colchicine, as an adjunct to anti-inflammatory therapy, appears to be an inexpensive and safe means to hasten symptom resolution, improving remission rates by one week, and to reduce further recurrences during follow-up," said Dr. Imazio of the Maria Vittoria Hospital in Turin, Italy.

Invited discussant Dr. Andre Keren, director of the Heart Failure and Heart Muscle Disease Center at the Heart Institute at Hadassah University Hospital in Jerusalem, described CORP as a well-designed and carefully performed trial. Its results strongly support the use of low-dose colchicine as a safe, well-tolerated, and effective first-line adjuvant to standard treatment in patients with recurrent pericarditis.

"I really believe that the time has arrived that colchicine should be more freely used," he said.

Both Dr. Imazio and Dr. Keren observed that the results may not be applicable to all patients with pericarditis since the trial excluded those patients with neoplastic or bacterial etiologies for their pericarditis as well as patients with multiple recurrences of pericarditis.

In addition, the drug’s "remarkable" safety and tolerability profile might have been influenced by careful patient selection and the low doses employed in the study, Dr. Keren said.

Based on nonrandomized observational findings and expert opinion, the European Society of Cardiology guidelines recommend colchicine 2 mg/day for 1 to 2 days, followed by a maintenance dose of 1 mg/day for the treatment of recurrent pericarditis.

The CORP investigators randomized patients from four Italian centers to conventional therapy plus placebo or colchicine for 6 months at the recommended doses for patients weighing at least 70 kg, but reduced the initial dose to 1 mg/day and the maintenance dose to 0.5 mg/day for those weighing less than 70 kg.

Conventional therapy was aspirin 800 mg-1,000 mg or ibuprofen 600 mg every 8 hours for 7-10 days, with the second choice being prednisone 0.2-0.5 mg/kg of body weight per day for 4 weeks and then gradually tapered.

Dr. Keren pointed out that the dose as well as the frequency of corticosteroids was lower in CORP than the researchers’ earlier CORE trial, in which prednisone was dosed at 1.0-1.5 mg/kg of body weight per day for 4 weeks, and 35% of patients had received steroids during the initial episode of pericarditis. In contrast, only 10% of placebo and 8% of colchicine patients in CORP had previously received corticosteroids.

"This might also reflect, in my view, a change in our perception that steroids can actually be deleterious in decreasing the recurrence rate," Dr. Keren said.

Symptom persistence at 72 hours was significantly lower in the colchicine group than in the placebo group (23% vs. 53%, P = .001), as was the rate of remission at 1 week (48% vs. 82%, P less than .001), Dr. Imazio said.

The mean number of recurrences was significantly lower in the colchicine-treated group than in the placebo group (0.1 vs. 1.0), and the time to first recurrence was also significantly longer at 2.5 months vs. 1 month (both P less than .001).

No significant differences were observed between the two groups in rates of readmission (5% vs. 13%), tamponade (0% vs. 2%), or constriction (0% both).

Gastrointestinal intolerance was the most common side effect, reported in four colchicine- and five placebo-treated patients. No severe side effects were observed in either group. Treatment discontinuation occurred in five colchicine and four placebo patients, Dr. Imazio said.

Full results of CORP are available online in the Annals of Internal Medicine (Ann. Intern. Med. 2011 Aug. 28 [Epub ahead of print]).

Dr. Imazio and his coauthors report no study sponsorship or conflicts. Dr. Keren reports no disclosures.

PARIS – In patients with a first recurrence of pericarditis, adding low-dose colchicine to standard therapy halved the risk of subsequent episodes of pericarditis.

Among 120 patients with a first recurrence of pericarditis in the Study of Colchicine to Treat and Prevent Recurrent Pericarditis (CORP) trial, the rate at 18 months of another recurrence was 24% with colchicine and standard therapy and 55% with placebo and standard therapy (P value less than .001).

The relative risk reduction associated with adjuvant colchicine was 56% and the number needed to treat to prevent one recurrence was three, Dr. Massimo Imazio reported at the annual congress of the European Society of Cardiology.

Colchicine (Colcrys) has been used for years to treat gout, and is the first drug to be shown in a double-blind, randomized placebo-controlled trial to prevent recurrent pericarditis.

"Following an initial episode of recurrent pericarditis, colchicine, as an adjunct to anti-inflammatory therapy, appears to be an inexpensive and safe means to hasten symptom resolution, improving remission rates by one week, and to reduce further recurrences during follow-up," said Dr. Imazio of the Maria Vittoria Hospital in Turin, Italy.

Invited discussant Dr. Andre Keren, director of the Heart Failure and Heart Muscle Disease Center at the Heart Institute at Hadassah University Hospital in Jerusalem, described CORP as a well-designed and carefully performed trial. Its results strongly support the use of low-dose colchicine as a safe, well-tolerated, and effective first-line adjuvant to standard treatment in patients with recurrent pericarditis.

"I really believe that the time has arrived that colchicine should be more freely used," he said.

Both Dr. Imazio and Dr. Keren observed that the results may not be applicable to all patients with pericarditis since the trial excluded those patients with neoplastic or bacterial etiologies for their pericarditis as well as patients with multiple recurrences of pericarditis.

In addition, the drug’s "remarkable" safety and tolerability profile might have been influenced by careful patient selection and the low doses employed in the study, Dr. Keren said.

Based on nonrandomized observational findings and expert opinion, the European Society of Cardiology guidelines recommend colchicine 2 mg/day for 1 to 2 days, followed by a maintenance dose of 1 mg/day for the treatment of recurrent pericarditis.

The CORP investigators randomized patients from four Italian centers to conventional therapy plus placebo or colchicine for 6 months at the recommended doses for patients weighing at least 70 kg, but reduced the initial dose to 1 mg/day and the maintenance dose to 0.5 mg/day for those weighing less than 70 kg.

Conventional therapy was aspirin 800 mg-1,000 mg or ibuprofen 600 mg every 8 hours for 7-10 days, with the second choice being prednisone 0.2-0.5 mg/kg of body weight per day for 4 weeks and then gradually tapered.

Dr. Keren pointed out that the dose as well as the frequency of corticosteroids was lower in CORP than the researchers’ earlier CORE trial, in which prednisone was dosed at 1.0-1.5 mg/kg of body weight per day for 4 weeks, and 35% of patients had received steroids during the initial episode of pericarditis. In contrast, only 10% of placebo and 8% of colchicine patients in CORP had previously received corticosteroids.

"This might also reflect, in my view, a change in our perception that steroids can actually be deleterious in decreasing the recurrence rate," Dr. Keren said.

Symptom persistence at 72 hours was significantly lower in the colchicine group than in the placebo group (23% vs. 53%, P = .001), as was the rate of remission at 1 week (48% vs. 82%, P less than .001), Dr. Imazio said.

The mean number of recurrences was significantly lower in the colchicine-treated group than in the placebo group (0.1 vs. 1.0), and the time to first recurrence was also significantly longer at 2.5 months vs. 1 month (both P less than .001).

No significant differences were observed between the two groups in rates of readmission (5% vs. 13%), tamponade (0% vs. 2%), or constriction (0% both).

Gastrointestinal intolerance was the most common side effect, reported in four colchicine- and five placebo-treated patients. No severe side effects were observed in either group. Treatment discontinuation occurred in five colchicine and four placebo patients, Dr. Imazio said.

Full results of CORP are available online in the Annals of Internal Medicine (Ann. Intern. Med. 2011 Aug. 28 [Epub ahead of print]).

Dr. Imazio and his coauthors report no study sponsorship or conflicts. Dr. Keren reports no disclosures.

PARIS – In patients with a first recurrence of pericarditis, adding low-dose colchicine to standard therapy halved the risk of subsequent episodes of pericarditis.

Among 120 patients with a first recurrence of pericarditis in the Study of Colchicine to Treat and Prevent Recurrent Pericarditis (CORP) trial, the rate at 18 months of another recurrence was 24% with colchicine and standard therapy and 55% with placebo and standard therapy (P value less than .001).

The relative risk reduction associated with adjuvant colchicine was 56% and the number needed to treat to prevent one recurrence was three, Dr. Massimo Imazio reported at the annual congress of the European Society of Cardiology.

Colchicine (Colcrys) has been used for years to treat gout, and is the first drug to be shown in a double-blind, randomized placebo-controlled trial to prevent recurrent pericarditis.

"Following an initial episode of recurrent pericarditis, colchicine, as an adjunct to anti-inflammatory therapy, appears to be an inexpensive and safe means to hasten symptom resolution, improving remission rates by one week, and to reduce further recurrences during follow-up," said Dr. Imazio of the Maria Vittoria Hospital in Turin, Italy.

Invited discussant Dr. Andre Keren, director of the Heart Failure and Heart Muscle Disease Center at the Heart Institute at Hadassah University Hospital in Jerusalem, described CORP as a well-designed and carefully performed trial. Its results strongly support the use of low-dose colchicine as a safe, well-tolerated, and effective first-line adjuvant to standard treatment in patients with recurrent pericarditis.

"I really believe that the time has arrived that colchicine should be more freely used," he said.

Both Dr. Imazio and Dr. Keren observed that the results may not be applicable to all patients with pericarditis since the trial excluded those patients with neoplastic or bacterial etiologies for their pericarditis as well as patients with multiple recurrences of pericarditis.

In addition, the drug’s "remarkable" safety and tolerability profile might have been influenced by careful patient selection and the low doses employed in the study, Dr. Keren said.

Based on nonrandomized observational findings and expert opinion, the European Society of Cardiology guidelines recommend colchicine 2 mg/day for 1 to 2 days, followed by a maintenance dose of 1 mg/day for the treatment of recurrent pericarditis.

The CORP investigators randomized patients from four Italian centers to conventional therapy plus placebo or colchicine for 6 months at the recommended doses for patients weighing at least 70 kg, but reduced the initial dose to 1 mg/day and the maintenance dose to 0.5 mg/day for those weighing less than 70 kg.

Conventional therapy was aspirin 800 mg-1,000 mg or ibuprofen 600 mg every 8 hours for 7-10 days, with the second choice being prednisone 0.2-0.5 mg/kg of body weight per day for 4 weeks and then gradually tapered.

Dr. Keren pointed out that the dose as well as the frequency of corticosteroids was lower in CORP than the researchers’ earlier CORE trial, in which prednisone was dosed at 1.0-1.5 mg/kg of body weight per day for 4 weeks, and 35% of patients had received steroids during the initial episode of pericarditis. In contrast, only 10% of placebo and 8% of colchicine patients in CORP had previously received corticosteroids.

"This might also reflect, in my view, a change in our perception that steroids can actually be deleterious in decreasing the recurrence rate," Dr. Keren said.

Symptom persistence at 72 hours was significantly lower in the colchicine group than in the placebo group (23% vs. 53%, P = .001), as was the rate of remission at 1 week (48% vs. 82%, P less than .001), Dr. Imazio said.

The mean number of recurrences was significantly lower in the colchicine-treated group than in the placebo group (0.1 vs. 1.0), and the time to first recurrence was also significantly longer at 2.5 months vs. 1 month (both P less than .001).

No significant differences were observed between the two groups in rates of readmission (5% vs. 13%), tamponade (0% vs. 2%), or constriction (0% both).

Gastrointestinal intolerance was the most common side effect, reported in four colchicine- and five placebo-treated patients. No severe side effects were observed in either group. Treatment discontinuation occurred in five colchicine and four placebo patients, Dr. Imazio said.

Full results of CORP are available online in the Annals of Internal Medicine (Ann. Intern. Med. 2011 Aug. 28 [Epub ahead of print]).

Dr. Imazio and his coauthors report no study sponsorship or conflicts. Dr. Keren reports no disclosures.

PARIS – Patients with diabetes who received insulin treatment faced a markedly increased risk of death in a review of more than 3,400 French adults who were followed for 14 years.

Diabetes patients "treated with insulin at baseline were at increased risk of all-cause mortality," Dr. Emilie Bérard said at the annual congress of the European Society of Cardiology. This finding "provides further information to the debate on the risks and benefits of increasing hypoglycemic treatments" in patients with diabetes, said Dr. Bérard, an epidemiology researcher at Toulouse (France) University Hospital Center.

After adjustment for several potential confounding factors, patients with diabetes who received insulin treatment had a fivefold increased risk for death during a 14-year period, compared with adults without diabetes. In contrast, patients with diabetes who received treatment with other hypoglycemic drugs – metformin or a sulfonylurea – had relative risks of 1.5- to 2.2-fold higher than did those without diabetes. In fact, the relative risk for death faced by patients with diabetes who were treated nearly doubled the relative risk faced by patients with diabetes who received no treatment at all at the time they entered the study, whose risk for death ran about 2.8-fold above that of the people without diabetes.

This study "is on the right track," but the findings must also "be taken with a grain of salt," commented Dr. Lars Rydén, professor of medicine at Uppsala (Sweden) University. "The results indicate something, but we need further studies." The main potential flaw in Dr. Bérard’s analysis is that it applied several adjusters in an analysis of a relatively small group of 171 patients with diabetes. "I think [the analysis] is on the edge of controlling for too many things in a small number of people, which led to extremely wide confidence intervals," he said.

Another limitation of the study was that when the participants were initially assessed in 1995-1996, they did not undergo measurement of their hemoglobin A_1c, which meant that the adjusted analysis could not take into account the quality of diabetes control that patients received at baseline, Dr. Bérard said. She speculated that insulin may have boosted mortality by leading to a relatively high rate of hypoglycemia, it may have caused weight gain, or it may be a marker for more serious diabetes. In addition, insulin treatment may have caused cardiovascular morbidity or mortality by stimulating the sympathetic nervous system and triggering vasoconstriction and promoting atherosclerosis.

Her analysis used data collected from 3,403 randomly selected French adults aged 34-64 in 1995-1996 as part of the third French survey performed as part of the MONICA (Multinational Monitoring of Trends and Developments in Cardiovascular Disease) project, a study sponsored by the World Health Organization. This group included 171 patients with diabetes, including 123 on some sort of hypoglycemic regimen and 48 who were not on any treatment at the time of their entry into MONICA. The treated patients comprised 37 on metformin only, 59 on a sulfonylurea alone or in combination with another hypoglycemic drug other than insulin, 16 on insulin only or in combination with a drug other than a sulfonylurea, and 11 on some other regimen.

Dr. Bérard and her associates determined the vital status of these people 14 years after their initial assessment for MONICA, and found that the mortality rates during that period ranged from 7% in the people without diabetes to 33% in those treated with insulin. Patients with diabetes who received no hypoglycemic treatment at baseline had a 23% mortality rate during follow-up.

The adjusted analysis controlled for demographic factors, duration of diabetes, history of diabetes complications, serious chronic comorbidities, alcohol use, smoking, blood pressure, and other potential confounders.

MONICA is sponsored by the World Health Organization. Dr. Bérard said that she had no disclosures.

PARIS – Patients with diabetes who received insulin treatment faced a markedly increased risk of death in a review of more than 3,400 French adults who were followed for 14 years.

Diabetes patients "treated with insulin at baseline were at increased risk of all-cause mortality," Dr. Emilie Bérard said at the annual congress of the European Society of Cardiology. This finding "provides further information to the debate on the risks and benefits of increasing hypoglycemic treatments" in patients with diabetes, said Dr. Bérard, an epidemiology researcher at Toulouse (France) University Hospital Center.

After adjustment for several potential confounding factors, patients with diabetes who received insulin treatment had a fivefold increased risk for death during a 14-year period, compared with adults without diabetes. In contrast, patients with diabetes who received treatment with other hypoglycemic drugs – metformin or a sulfonylurea – had relative risks of 1.5- to 2.2-fold higher than did those without diabetes. In fact, the relative risk for death faced by patients with diabetes who were treated nearly doubled the relative risk faced by patients with diabetes who received no treatment at all at the time they entered the study, whose risk for death ran about 2.8-fold above that of the people without diabetes.

This study "is on the right track," but the findings must also "be taken with a grain of salt," commented Dr. Lars Rydén, professor of medicine at Uppsala (Sweden) University. "The results indicate something, but we need further studies." The main potential flaw in Dr. Bérard’s analysis is that it applied several adjusters in an analysis of a relatively small group of 171 patients with diabetes. "I think [the analysis] is on the edge of controlling for too many things in a small number of people, which led to extremely wide confidence intervals," he said.

Another limitation of the study was that when the participants were initially assessed in 1995-1996, they did not undergo measurement of their hemoglobin A_1c, which meant that the adjusted analysis could not take into account the quality of diabetes control that patients received at baseline, Dr. Bérard said. She speculated that insulin may have boosted mortality by leading to a relatively high rate of hypoglycemia, it may have caused weight gain, or it may be a marker for more serious diabetes. In addition, insulin treatment may have caused cardiovascular morbidity or mortality by stimulating the sympathetic nervous system and triggering vasoconstriction and promoting atherosclerosis.

Her analysis used data collected from 3,403 randomly selected French adults aged 34-64 in 1995-1996 as part of the third French survey performed as part of the MONICA (Multinational Monitoring of Trends and Developments in Cardiovascular Disease) project, a study sponsored by the World Health Organization. This group included 171 patients with diabetes, including 123 on some sort of hypoglycemic regimen and 48 who were not on any treatment at the time of their entry into MONICA. The treated patients comprised 37 on metformin only, 59 on a sulfonylurea alone or in combination with another hypoglycemic drug other than insulin, 16 on insulin only or in combination with a drug other than a sulfonylurea, and 11 on some other regimen.

Dr. Bérard and her associates determined the vital status of these people 14 years after their initial assessment for MONICA, and found that the mortality rates during that period ranged from 7% in the people without diabetes to 33% in those treated with insulin. Patients with diabetes who received no hypoglycemic treatment at baseline had a 23% mortality rate during follow-up.

The adjusted analysis controlled for demographic factors, duration of diabetes, history of diabetes complications, serious chronic comorbidities, alcohol use, smoking, blood pressure, and other potential confounders.

MONICA is sponsored by the World Health Organization. Dr. Bérard said that she had no disclosures.

PARIS – Patients with diabetes who received insulin treatment faced a markedly increased risk of death in a review of more than 3,400 French adults who were followed for 14 years.

Diabetes patients "treated with insulin at baseline were at increased risk of all-cause mortality," Dr. Emilie Bérard said at the annual congress of the European Society of Cardiology. This finding "provides further information to the debate on the risks and benefits of increasing hypoglycemic treatments" in patients with diabetes, said Dr. Bérard, an epidemiology researcher at Toulouse (France) University Hospital Center.

After adjustment for several potential confounding factors, patients with diabetes who received insulin treatment had a fivefold increased risk for death during a 14-year period, compared with adults without diabetes. In contrast, patients with diabetes who received treatment with other hypoglycemic drugs – metformin or a sulfonylurea – had relative risks of 1.5- to 2.2-fold higher than did those without diabetes. In fact, the relative risk for death faced by patients with diabetes who were treated nearly doubled the relative risk faced by patients with diabetes who received no treatment at all at the time they entered the study, whose risk for death ran about 2.8-fold above that of the people without diabetes.

This study "is on the right track," but the findings must also "be taken with a grain of salt," commented Dr. Lars Rydén, professor of medicine at Uppsala (Sweden) University. "The results indicate something, but we need further studies." The main potential flaw in Dr. Bérard’s analysis is that it applied several adjusters in an analysis of a relatively small group of 171 patients with diabetes. "I think [the analysis] is on the edge of controlling for too many things in a small number of people, which led to extremely wide confidence intervals," he said.

Another limitation of the study was that when the participants were initially assessed in 1995-1996, they did not undergo measurement of their hemoglobin A_1c, which meant that the adjusted analysis could not take into account the quality of diabetes control that patients received at baseline, Dr. Bérard said. She speculated that insulin may have boosted mortality by leading to a relatively high rate of hypoglycemia, it may have caused weight gain, or it may be a marker for more serious diabetes. In addition, insulin treatment may have caused cardiovascular morbidity or mortality by stimulating the sympathetic nervous system and triggering vasoconstriction and promoting atherosclerosis.

Her analysis used data collected from 3,403 randomly selected French adults aged 34-64 in 1995-1996 as part of the third French survey performed as part of the MONICA (Multinational Monitoring of Trends and Developments in Cardiovascular Disease) project, a study sponsored by the World Health Organization. This group included 171 patients with diabetes, including 123 on some sort of hypoglycemic regimen and 48 who were not on any treatment at the time of their entry into MONICA. The treated patients comprised 37 on metformin only, 59 on a sulfonylurea alone or in combination with another hypoglycemic drug other than insulin, 16 on insulin only or in combination with a drug other than a sulfonylurea, and 11 on some other regimen.

Dr. Bérard and her associates determined the vital status of these people 14 years after their initial assessment for MONICA, and found that the mortality rates during that period ranged from 7% in the people without diabetes to 33% in those treated with insulin. Patients with diabetes who received no hypoglycemic treatment at baseline had a 23% mortality rate during follow-up.

The adjusted analysis controlled for demographic factors, duration of diabetes, history of diabetes complications, serious chronic comorbidities, alcohol use, smoking, blood pressure, and other potential confounders.

MONICA is sponsored by the World Health Organization. Dr. Bérard said that she had no disclosures.

PARIS – Up to 24 months of dual antiplatelet therapy after coronary stent implantation was no more effective than was 6 months and significantly increased the risk of hemorrhage in a multicenter, randomized study of 1,970 patients.

In the Prolonging Dual Antiplatelet Treatment after Grading Stent-induced Intimal Hyperplasia Study (PRODIGY), 10% of the 983 patients who took clopidogrel plus aspirin for 6 months after stent implantation and 10% of 987 patients who took the dual antiplatelet therapy for up to 24 months died or had a nonfatal MI or a cerebrovascular accident.

Individual rates for death, MI, cerebrovascular accident, or stent thrombosis also did not differ significantly between groups, Dr. Marco Valgimigli and his associates reported at the annual congress of the European Society of Cardiology. Death rates were 10% in the 6-month group and 9% with prolonged therapy.

Among those on the longer dual antiplatelet therapy, however, the risk of type II, III or V bleeding was twice that of the 6-month therapy group during the 24 months of follow-up, said Dr. Valgimigli of University Hospital, Ferrara, Italy. Bleeds occurred in 7.4% of the extended-therapy group and in 3.5% of the 6-month therapy group.

The study used prespecified definitions of bleeding, including the recently proposed Bleeding Academic Research Consortium classification.

The risks of major bleeding defined by Thrombolysis in Myocardial Infarction (TIMI) also were significantly higher in the prolonged-therapy group (2% on prolonged therapy vs. 1% on 6-month therapy). Red blood cell transfusions were needed in 3% on prolonged therapy and 1% on 6-month therapy, a significant difference.

Adults who were scheduled for elective, urgent, or emergency coronary angioplasty were randomized in a 1:1:1:1 fashion to receive an everolimus-eluting stent, a paclitaxel-eluting stent, a zotarolimus-eluting stent, or a third-generation thin-strut bare-metal stent. Thirty days later, they were randomized again to either 6 or 24 months of clopidogrel as add-on therapy to aspirin.

Patients received stents due to chronic stable coronary artery disease or acute coronary syndromes including ST-elevation MI and non–ST-elevation MI.

Current guidelines call for at least 12 months of dual antiplatelet therapy in patients receiving drug-eluting stents, based mainly on data from registries.

With dual antiplatelet therapy lasting more than 6 months, "The risk of bleeding is surely higher than the possible benefit for ischemia," Dr. Valgimigli said. "We have not seen any signs suggesting that prolonged dual antiplatelet therapy is better than short."

Results Inform Antiplatelet Duration After Drug-Eluting Stents

"This all kind of stems from the only two big studies of bare-metal stents that address the question of how long to use dual antiplatelet therapy after somebody gets a stent: the PCI-CURE trial [Percutaneous Coronary Intervention–Clopidogrel in Unstable Angina to Prevent Recurrent Events, N. Engl. J. Med. 2001;345:494-502] and CREDO [Clopidogrel for the Reduction of Events During Observation, JAMA 2002;288:2411-20]," Dr. Gordon F. Tomaselli said in an interview.

The recommendations from American Heart Association guidelines in 2005 after looking at CURE-PCI and CREDO were that people should get at least a month and optimally a year of dual antiplatelet therapy for a bare-metal stent, he said.

"There wasn’t anything known initially about drug-eluting stents until we started to see some late stent thromboses. They’re rare, but with profound complications including death and MI, so preventing them was of paramount importance," said Dr. Tomaselli, chief of cardiology at Johns Hopkins University, Baltimore, and president of the American Heart Association. "We didn’t really know what the duration of dual antiplatelet therapy should be with drug-eluting stents. The recommendation that came out was that it should be at least a year. Whether or not that’s right, nobody has any clue. A randomized trial is the way to go."

The PRODIGY trial certainly is going to add to the information that can be used for a clinical trial update regarding duration of dual antiplatelet therapy, he said. "Will this be sufficient to change the recommendation? I’m not really sure, but it’s certainly something we need to think about considering the increased incidence of bleeding with longer duration therapy.

"It always is complicated for us because these patients have other problems that often require things like surgery. Getting them off of dual antiplatelet therapy earlier rather than later is usually a good thing."

Dr. Tomaselli said he has no relevant conflicts of interest.

Dr. Valgimigli’s university sponsored the study. He has received research funds from, or been an adviser or speaker for, Merck, Iroko, Eli Lilly, Medtronic, The Medicines Company, Daiichi Sankyo, St. Jude, Abbott Vascular, Cordis, CID, Terumo, and Accumetrics.

To watch a video interview of Dr. Tomaselli, go to http://www.youtube.com/watch?v=8vWiSqTK1Do.

PARIS – Up to 24 months of dual antiplatelet therapy after coronary stent implantation was no more effective than was 6 months and significantly increased the risk of hemorrhage in a multicenter, randomized study of 1,970 patients.

In the Prolonging Dual Antiplatelet Treatment after Grading Stent-induced Intimal Hyperplasia Study (PRODIGY), 10% of the 983 patients who took clopidogrel plus aspirin for 6 months after stent implantation and 10% of 987 patients who took the dual antiplatelet therapy for up to 24 months died or had a nonfatal MI or a cerebrovascular accident.

Individual rates for death, MI, cerebrovascular accident, or stent thrombosis also did not differ significantly between groups, Dr. Marco Valgimigli and his associates reported at the annual congress of the European Society of Cardiology. Death rates were 10% in the 6-month group and 9% with prolonged therapy.

Among those on the longer dual antiplatelet therapy, however, the risk of type II, III or V bleeding was twice that of the 6-month therapy group during the 24 months of follow-up, said Dr. Valgimigli of University Hospital, Ferrara, Italy. Bleeds occurred in 7.4% of the extended-therapy group and in 3.5% of the 6-month therapy group.

The study used prespecified definitions of bleeding, including the recently proposed Bleeding Academic Research Consortium classification.

The risks of major bleeding defined by Thrombolysis in Myocardial Infarction (TIMI) also were significantly higher in the prolonged-therapy group (2% on prolonged therapy vs. 1% on 6-month therapy). Red blood cell transfusions were needed in 3% on prolonged therapy and 1% on 6-month therapy, a significant difference.

Adults who were scheduled for elective, urgent, or emergency coronary angioplasty were randomized in a 1:1:1:1 fashion to receive an everolimus-eluting stent, a paclitaxel-eluting stent, a zotarolimus-eluting stent, or a third-generation thin-strut bare-metal stent. Thirty days later, they were randomized again to either 6 or 24 months of clopidogrel as add-on therapy to aspirin.

Patients received stents due to chronic stable coronary artery disease or acute coronary syndromes including ST-elevation MI and non–ST-elevation MI.

Current guidelines call for at least 12 months of dual antiplatelet therapy in patients receiving drug-eluting stents, based mainly on data from registries.

With dual antiplatelet therapy lasting more than 6 months, "The risk of bleeding is surely higher than the possible benefit for ischemia," Dr. Valgimigli said. "We have not seen any signs suggesting that prolonged dual antiplatelet therapy is better than short."

Results Inform Antiplatelet Duration After Drug-Eluting Stents

"This all kind of stems from the only two big studies of bare-metal stents that address the question of how long to use dual antiplatelet therapy after somebody gets a stent: the PCI-CURE trial [Percutaneous Coronary Intervention–Clopidogrel in Unstable Angina to Prevent Recurrent Events, N. Engl. J. Med. 2001;345:494-502] and CREDO [Clopidogrel for the Reduction of Events During Observation, JAMA 2002;288:2411-20]," Dr. Gordon F. Tomaselli said in an interview.

The recommendations from American Heart Association guidelines in 2005 after looking at CURE-PCI and CREDO were that people should get at least a month and optimally a year of dual antiplatelet therapy for a bare-metal stent, he said.

"There wasn’t anything known initially about drug-eluting stents until we started to see some late stent thromboses. They’re rare, but with profound complications including death and MI, so preventing them was of paramount importance," said Dr. Tomaselli, chief of cardiology at Johns Hopkins University, Baltimore, and president of the American Heart Association. "We didn’t really know what the duration of dual antiplatelet therapy should be with drug-eluting stents. The recommendation that came out was that it should be at least a year. Whether or not that’s right, nobody has any clue. A randomized trial is the way to go."

The PRODIGY trial certainly is going to add to the information that can be used for a clinical trial update regarding duration of dual antiplatelet therapy, he said. "Will this be sufficient to change the recommendation? I’m not really sure, but it’s certainly something we need to think about considering the increased incidence of bleeding with longer duration therapy.

"It always is complicated for us because these patients have other problems that often require things like surgery. Getting them off of dual antiplatelet therapy earlier rather than later is usually a good thing."

Dr. Tomaselli said he has no relevant conflicts of interest.

Dr. Valgimigli’s university sponsored the study. He has received research funds from, or been an adviser or speaker for, Merck, Iroko, Eli Lilly, Medtronic, The Medicines Company, Daiichi Sankyo, St. Jude, Abbott Vascular, Cordis, CID, Terumo, and Accumetrics.

To watch a video interview of Dr. Tomaselli, go to http://www.youtube.com/watch?v=8vWiSqTK1Do.

PARIS – Up to 24 months of dual antiplatelet therapy after coronary stent implantation was no more effective than was 6 months and significantly increased the risk of hemorrhage in a multicenter, randomized study of 1,970 patients.

In the Prolonging Dual Antiplatelet Treatment after Grading Stent-induced Intimal Hyperplasia Study (PRODIGY), 10% of the 983 patients who took clopidogrel plus aspirin for 6 months after stent implantation and 10% of 987 patients who took the dual antiplatelet therapy for up to 24 months died or had a nonfatal MI or a cerebrovascular accident.

Individual rates for death, MI, cerebrovascular accident, or stent thrombosis also did not differ significantly between groups, Dr. Marco Valgimigli and his associates reported at the annual congress of the European Society of Cardiology. Death rates were 10% in the 6-month group and 9% with prolonged therapy.

Among those on the longer dual antiplatelet therapy, however, the risk of type II, III or V bleeding was twice that of the 6-month therapy group during the 24 months of follow-up, said Dr. Valgimigli of University Hospital, Ferrara, Italy. Bleeds occurred in 7.4% of the extended-therapy group and in 3.5% of the 6-month therapy group.

The study used prespecified definitions of bleeding, including the recently proposed Bleeding Academic Research Consortium classification.

The risks of major bleeding defined by Thrombolysis in Myocardial Infarction (TIMI) also were significantly higher in the prolonged-therapy group (2% on prolonged therapy vs. 1% on 6-month therapy). Red blood cell transfusions were needed in 3% on prolonged therapy and 1% on 6-month therapy, a significant difference.

Adults who were scheduled for elective, urgent, or emergency coronary angioplasty were randomized in a 1:1:1:1 fashion to receive an everolimus-eluting stent, a paclitaxel-eluting stent, a zotarolimus-eluting stent, or a third-generation thin-strut bare-metal stent. Thirty days later, they were randomized again to either 6 or 24 months of clopidogrel as add-on therapy to aspirin.

Patients received stents due to chronic stable coronary artery disease or acute coronary syndromes including ST-elevation MI and non–ST-elevation MI.

Current guidelines call for at least 12 months of dual antiplatelet therapy in patients receiving drug-eluting stents, based mainly on data from registries.

With dual antiplatelet therapy lasting more than 6 months, "The risk of bleeding is surely higher than the possible benefit for ischemia," Dr. Valgimigli said. "We have not seen any signs suggesting that prolonged dual antiplatelet therapy is better than short."

Results Inform Antiplatelet Duration After Drug-Eluting Stents

"This all kind of stems from the only two big studies of bare-metal stents that address the question of how long to use dual antiplatelet therapy after somebody gets a stent: the PCI-CURE trial [Percutaneous Coronary Intervention–Clopidogrel in Unstable Angina to Prevent Recurrent Events, N. Engl. J. Med. 2001;345:494-502] and CREDO [Clopidogrel for the Reduction of Events During Observation, JAMA 2002;288:2411-20]," Dr. Gordon F. Tomaselli said in an interview.

The recommendations from American Heart Association guidelines in 2005 after looking at CURE-PCI and CREDO were that people should get at least a month and optimally a year of dual antiplatelet therapy for a bare-metal stent, he said.

"There wasn’t anything known initially about drug-eluting stents until we started to see some late stent thromboses. They’re rare, but with profound complications including death and MI, so preventing them was of paramount importance," said Dr. Tomaselli, chief of cardiology at Johns Hopkins University, Baltimore, and president of the American Heart Association. "We didn’t really know what the duration of dual antiplatelet therapy should be with drug-eluting stents. The recommendation that came out was that it should be at least a year. Whether or not that’s right, nobody has any clue. A randomized trial is the way to go."

The PRODIGY trial certainly is going to add to the information that can be used for a clinical trial update regarding duration of dual antiplatelet therapy, he said. "Will this be sufficient to change the recommendation? I’m not really sure, but it’s certainly something we need to think about considering the increased incidence of bleeding with longer duration therapy.

"It always is complicated for us because these patients have other problems that often require things like surgery. Getting them off of dual antiplatelet therapy earlier rather than later is usually a good thing."

Dr. Tomaselli said he has no relevant conflicts of interest.

Dr. Valgimigli’s university sponsored the study. He has received research funds from, or been an adviser or speaker for, Merck, Iroko, Eli Lilly, Medtronic, The Medicines Company, Daiichi Sankyo, St. Jude, Abbott Vascular, Cordis, CID, Terumo, and Accumetrics.

To watch a video interview of Dr. Tomaselli, go to http://www.youtube.com/watch?v=8vWiSqTK1Do.

PARIS – The current master of the coronary drug-eluting stent universe, the everolimus-eluting stent, finally proved itself fully worthy of its position, matching the efficacy and safety performance of its predecessor, the sirolimus-eluting coronary stent.

"The sirolimus-eluting stent was the most widely used and extensively studied first-generation drug-eluting stent. The clinical outcomes of the sirolimus-eluting stent should be regarded as the benchmark for current and future second-generation drug-eluting stents," Dr. Takeshi Kimura said at the annual congress of the European Society of Cardiology. "In this large-scale, randomized, controlled trial comparing EES [everolimus-eluting stents] with SES [sirolimus-eluting stents], EES was demonstrated to be noninferior to SES with respect to target-lesion revascularization rate at 1 year and angiographic in-segment late loss at 8-12 months," said Dr. Kimura, professor of cardiovascular medicine at Kyoto (Japan) University.

"This study is important, because the sirolimus-eluting stent has been the standard of care. We have good, long-term results with the SES, and almost all we know about drug-eluting stents is from the SES," said Dr. Uwe Zeymer, an interventional cardiologist and professor at the Institute for MI Research in Ludwigshafen, Germany. Now that interventional cardiologists have broadly adopted EES as their primary tool in percutaneous coronary interventions, "it’s important to show they are as good and as safe as SES," he said in an interview. EES have largely replaced SES because they are easier to deliver into coronary arteries. "Now we can also say that EES equal the standard of care" for drug-eluting stents, the DES, for efficacy and safety. "It is reassuring."

The Randomized Evaluation of Sirolimus-Eluting versus Everolimus-Eluting Stent Trial (RESET) randomized 3,197 all-comer patients at 100 Japanese centers during February-June 2010. The patients had, on average, 1.2 coronary lesions each that required stenting, and each patient received an average of 1.5 stents.

After 12 months, the study’s primary clinical end point, need for target lesion revascularization, occurred in 4.3% of patients treated with EES and in 5.0% of those treated with SES, a difference that was not significantly different and that met the study’s prespecified criterion for noninferiority, Dr. Kimura reported.

Other safety and efficacy measures included the 1-year rate of all-cause death, myocardial infarction, stent thrombosis, and the rate after 8-12 months of in-segment and in-stent late loss. Patients who received EES and DES showed no statistically significant differences for any of these measures, and the rate of in-segment late loss also fell within the study’s prespecified criterion for noninferiority.

Longer-term follow-up is needed to see whether EES could reduce the rate of late adverse events, such as late restenosis or stent thrombosis, that occur more than 1 year after stent placement," Dr. Kimura said.

Dr. Kimura said that he has served on the scientific advisory board and has received honoraria from Abbott Vascular, Cordis Cardiology, and Terumo. Dr. Zeymer said that the Institute of MI Research in Germany, where he works, has received research grant support from multiple cardiac device companies.

PARIS – The current master of the coronary drug-eluting stent universe, the everolimus-eluting stent, finally proved itself fully worthy of its position, matching the efficacy and safety performance of its predecessor, the sirolimus-eluting coronary stent.

"The sirolimus-eluting stent was the most widely used and extensively studied first-generation drug-eluting stent. The clinical outcomes of the sirolimus-eluting stent should be regarded as the benchmark for current and future second-generation drug-eluting stents," Dr. Takeshi Kimura said at the annual congress of the European Society of Cardiology. "In this large-scale, randomized, controlled trial comparing EES [everolimus-eluting stents] with SES [sirolimus-eluting stents], EES was demonstrated to be noninferior to SES with respect to target-lesion revascularization rate at 1 year and angiographic in-segment late loss at 8-12 months," said Dr. Kimura, professor of cardiovascular medicine at Kyoto (Japan) University.

"This study is important, because the sirolimus-eluting stent has been the standard of care. We have good, long-term results with the SES, and almost all we know about drug-eluting stents is from the SES," said Dr. Uwe Zeymer, an interventional cardiologist and professor at the Institute for MI Research in Ludwigshafen, Germany. Now that interventional cardiologists have broadly adopted EES as their primary tool in percutaneous coronary interventions, "it’s important to show they are as good and as safe as SES," he said in an interview. EES have largely replaced SES because they are easier to deliver into coronary arteries. "Now we can also say that EES equal the standard of care" for drug-eluting stents, the DES, for efficacy and safety. "It is reassuring."

The Randomized Evaluation of Sirolimus-Eluting versus Everolimus-Eluting Stent Trial (RESET) randomized 3,197 all-comer patients at 100 Japanese centers during February-June 2010. The patients had, on average, 1.2 coronary lesions each that required stenting, and each patient received an average of 1.5 stents.

After 12 months, the study’s primary clinical end point, need for target lesion revascularization, occurred in 4.3% of patients treated with EES and in 5.0% of those treated with SES, a difference that was not significantly different and that met the study’s prespecified criterion for noninferiority, Dr. Kimura reported.

Other safety and efficacy measures included the 1-year rate of all-cause death, myocardial infarction, stent thrombosis, and the rate after 8-12 months of in-segment and in-stent late loss. Patients who received EES and DES showed no statistically significant differences for any of these measures, and the rate of in-segment late loss also fell within the study’s prespecified criterion for noninferiority.

Longer-term follow-up is needed to see whether EES could reduce the rate of late adverse events, such as late restenosis or stent thrombosis, that occur more than 1 year after stent placement," Dr. Kimura said.

Dr. Kimura said that he has served on the scientific advisory board and has received honoraria from Abbott Vascular, Cordis Cardiology, and Terumo. Dr. Zeymer said that the Institute of MI Research in Germany, where he works, has received research grant support from multiple cardiac device companies.

PARIS – The current master of the coronary drug-eluting stent universe, the everolimus-eluting stent, finally proved itself fully worthy of its position, matching the efficacy and safety performance of its predecessor, the sirolimus-eluting coronary stent.

"The sirolimus-eluting stent was the most widely used and extensively studied first-generation drug-eluting stent. The clinical outcomes of the sirolimus-eluting stent should be regarded as the benchmark for current and future second-generation drug-eluting stents," Dr. Takeshi Kimura said at the annual congress of the European Society of Cardiology. "In this large-scale, randomized, controlled trial comparing EES [everolimus-eluting stents] with SES [sirolimus-eluting stents], EES was demonstrated to be noninferior to SES with respect to target-lesion revascularization rate at 1 year and angiographic in-segment late loss at 8-12 months," said Dr. Kimura, professor of cardiovascular medicine at Kyoto (Japan) University.

"This study is important, because the sirolimus-eluting stent has been the standard of care. We have good, long-term results with the SES, and almost all we know about drug-eluting stents is from the SES," said Dr. Uwe Zeymer, an interventional cardiologist and professor at the Institute for MI Research in Ludwigshafen, Germany. Now that interventional cardiologists have broadly adopted EES as their primary tool in percutaneous coronary interventions, "it’s important to show they are as good and as safe as SES," he said in an interview. EES have largely replaced SES because they are easier to deliver into coronary arteries. "Now we can also say that EES equal the standard of care" for drug-eluting stents, the DES, for efficacy and safety. "It is reassuring."

The Randomized Evaluation of Sirolimus-Eluting versus Everolimus-Eluting Stent Trial (RESET) randomized 3,197 all-comer patients at 100 Japanese centers during February-June 2010. The patients had, on average, 1.2 coronary lesions each that required stenting, and each patient received an average of 1.5 stents.

After 12 months, the study’s primary clinical end point, need for target lesion revascularization, occurred in 4.3% of patients treated with EES and in 5.0% of those treated with SES, a difference that was not significantly different and that met the study’s prespecified criterion for noninferiority, Dr. Kimura reported.

Other safety and efficacy measures included the 1-year rate of all-cause death, myocardial infarction, stent thrombosis, and the rate after 8-12 months of in-segment and in-stent late loss. Patients who received EES and DES showed no statistically significant differences for any of these measures, and the rate of in-segment late loss also fell within the study’s prespecified criterion for noninferiority.

Longer-term follow-up is needed to see whether EES could reduce the rate of late adverse events, such as late restenosis or stent thrombosis, that occur more than 1 year after stent placement," Dr. Kimura said.

Dr. Kimura said that he has served on the scientific advisory board and has received honoraria from Abbott Vascular, Cordis Cardiology, and Terumo. Dr. Zeymer said that the Institute of MI Research in Germany, where he works, has received research grant support from multiple cardiac device companies.

PARIS – Intra-aortic counterpulsation balloon therapy during percutaneous coronary intervention did not reduce infarct size in patients with ST-elevation myocardial infarction without shock in the multicenter, international CRISP-AMI trial.

The findings do not, however, close the door on this widely used therapy, Dr. Manesh Patel said at the annual congress of the European Society of Cardiology.

"Clinicians should continue to be vigilant about identifying patients who are at risk for rapid deterioration or hypertension that may still benefit from support, as seen with the crossover in this trial," he said at the meeting.

In all, 8.5% of patients randomized to percutaneous coronary intervention (PCI) alone crossed over to rescue intra-aortic balloon counterpulsation (IABC) in the CRISP-AMI (Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction) study.

Among all 337 patients in the trial, mean infarct size was 42% of the left ventricle in patients randomized to IABC prior to PCI and continued for at least 12 hours and 37.5% in the PCI-alone group (P = .06), said Dr. Patel of the Duke Clinical Research Institute in Durham, N.C.

In patients with proximal left anterior descending and thrombolysis in myocardial infarction flow scores of 0 or 1, the mean infarct size was 46.7% of the left ventricle vs. 42.3%, respectively (P = .11).

Invited discussant Dr. Kurt Huber, director of the department of medicine, cardiology, and emergency medicine at Wilhelminenspital in Vienna, said, "I’m sure that this method is still important for certain patient groups."

He noted that American Heart Association guidelines recommend IABC for patients in cardiogenic shock, with a 1B recommendation.

Moreover, despite missing statistical significance, hard clinical end points were lower in the IABC arm, Dr. Huber said.

At 6 months, three patients in the IABC plus PCI group had died vs. nine in the PCI-alone group (P = .12).

An exploratory composite end point of time to death, shock, or new or worsening heart failure also favored the counterpulsation therapy plus PCI group over the PCI-alone group (8 events vs. 21 events, P = .03).

There was, however, a nonsignificant increase in side effects, particularly vascular complications, Dr. Huber said.

At 30 days, major vascular complications occurred in seven patients in the IABC plus PCI group vs. only two in the PCI-alone group (P = .09.). Major bleeding or transfusion occurred in five patients vs. three patients, respectively, Dr. Patel reported.

Dr. Huber said other studies are needed to define which patients might benefit from IABC. He highlighted the only other prospective trial of IACP, the TACTICS trial, in which IAPC failed to offer a survival benefit when added to fibrinolysis for patients with MI who were hemodynamically unstable, but suggested a possible benefit for patients with the most severe heart failure or hypertension (J. Thromb. Thrombolysis 2005;19:33-9).

Session comoderator Dr. Christodoulos Stefanadis of Athens University Medical School said in an interview that it is still acceptable to use IACP in both stable and unstable patients, but agreed that other studies are needed to resolve the issue.

"For many years, we believe that the use of the intra-aortic pump is an effective means to reduce infarct size and to reduce the mortality rate, especially in patients with cardiogenic shock," he said.

"In unstable patients, I personally believe that the use of the intra-aortic pump remains effective, but the question is what happens in stable patients without low blood pressure or shock."

At baseline, CRISP-AMI patients were hemodynamically stable, with a median systolic blood pressure of 130 mm Hg in the IABC plus PCI group and 135 mm Hg in the PCI-alone patients.

The time required to insert the intra-aortic balloon added just 9 minutes to the procedure, making it unlikely that this derailed the potential benefits of counterpulsation therapy, Dr. Patel said in an interview.

The results of CRISP-AMI were simultaneously published online by JAMA (2011 Aug. 30 [doi:10.1001/jama.2011.1280]).

Dr. Patel reported receiving grant funding and travel reimbursement from the study sponsor Maquet (formerly Datascope).

PARIS – Intra-aortic counterpulsation balloon therapy during percutaneous coronary intervention did not reduce infarct size in patients with ST-elevation myocardial infarction without shock in the multicenter, international CRISP-AMI trial.

The findings do not, however, close the door on this widely used therapy, Dr. Manesh Patel said at the annual congress of the European Society of Cardiology.

"Clinicians should continue to be vigilant about identifying patients who are at risk for rapid deterioration or hypertension that may still benefit from support, as seen with the crossover in this trial," he said at the meeting.

In all, 8.5% of patients randomized to percutaneous coronary intervention (PCI) alone crossed over to rescue intra-aortic balloon counterpulsation (IABC) in the CRISP-AMI (Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction) study.

Among all 337 patients in the trial, mean infarct size was 42% of the left ventricle in patients randomized to IABC prior to PCI and continued for at least 12 hours and 37.5% in the PCI-alone group (P = .06), said Dr. Patel of the Duke Clinical Research Institute in Durham, N.C.

In patients with proximal left anterior descending and thrombolysis in myocardial infarction flow scores of 0 or 1, the mean infarct size was 46.7% of the left ventricle vs. 42.3%, respectively (P = .11).

Invited discussant Dr. Kurt Huber, director of the department of medicine, cardiology, and emergency medicine at Wilhelminenspital in Vienna, said, "I’m sure that this method is still important for certain patient groups."

He noted that American Heart Association guidelines recommend IABC for patients in cardiogenic shock, with a 1B recommendation.

Moreover, despite missing statistical significance, hard clinical end points were lower in the IABC arm, Dr. Huber said.

At 6 months, three patients in the IABC plus PCI group had died vs. nine in the PCI-alone group (P = .12).

An exploratory composite end point of time to death, shock, or new or worsening heart failure also favored the counterpulsation therapy plus PCI group over the PCI-alone group (8 events vs. 21 events, P = .03).

There was, however, a nonsignificant increase in side effects, particularly vascular complications, Dr. Huber said.

At 30 days, major vascular complications occurred in seven patients in the IABC plus PCI group vs. only two in the PCI-alone group (P = .09.). Major bleeding or transfusion occurred in five patients vs. three patients, respectively, Dr. Patel reported.

Dr. Huber said other studies are needed to define which patients might benefit from IABC. He highlighted the only other prospective trial of IACP, the TACTICS trial, in which IAPC failed to offer a survival benefit when added to fibrinolysis for patients with MI who were hemodynamically unstable, but suggested a possible benefit for patients with the most severe heart failure or hypertension (J. Thromb. Thrombolysis 2005;19:33-9).

Session comoderator Dr. Christodoulos Stefanadis of Athens University Medical School said in an interview that it is still acceptable to use IACP in both stable and unstable patients, but agreed that other studies are needed to resolve the issue.

"For many years, we believe that the use of the intra-aortic pump is an effective means to reduce infarct size and to reduce the mortality rate, especially in patients with cardiogenic shock," he said.

"In unstable patients, I personally believe that the use of the intra-aortic pump remains effective, but the question is what happens in stable patients without low blood pressure or shock."

At baseline, CRISP-AMI patients were hemodynamically stable, with a median systolic blood pressure of 130 mm Hg in the IABC plus PCI group and 135 mm Hg in the PCI-alone patients.

The time required to insert the intra-aortic balloon added just 9 minutes to the procedure, making it unlikely that this derailed the potential benefits of counterpulsation therapy, Dr. Patel said in an interview.

The results of CRISP-AMI were simultaneously published online by JAMA (2011 Aug. 30 [doi:10.1001/jama.2011.1280]).

Dr. Patel reported receiving grant funding and travel reimbursement from the study sponsor Maquet (formerly Datascope).

PARIS – Intra-aortic counterpulsation balloon therapy during percutaneous coronary intervention did not reduce infarct size in patients with ST-elevation myocardial infarction without shock in the multicenter, international CRISP-AMI trial.

The findings do not, however, close the door on this widely used therapy, Dr. Manesh Patel said at the annual congress of the European Society of Cardiology.

"Clinicians should continue to be vigilant about identifying patients who are at risk for rapid deterioration or hypertension that may still benefit from support, as seen with the crossover in this trial," he said at the meeting.

In all, 8.5% of patients randomized to percutaneous coronary intervention (PCI) alone crossed over to rescue intra-aortic balloon counterpulsation (IABC) in the CRISP-AMI (Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction) study.

Among all 337 patients in the trial, mean infarct size was 42% of the left ventricle in patients randomized to IABC prior to PCI and continued for at least 12 hours and 37.5% in the PCI-alone group (P = .06), said Dr. Patel of the Duke Clinical Research Institute in Durham, N.C.

In patients with proximal left anterior descending and thrombolysis in myocardial infarction flow scores of 0 or 1, the mean infarct size was 46.7% of the left ventricle vs. 42.3%, respectively (P = .11).

Invited discussant Dr. Kurt Huber, director of the department of medicine, cardiology, and emergency medicine at Wilhelminenspital in Vienna, said, "I’m sure that this method is still important for certain patient groups."

He noted that American Heart Association guidelines recommend IABC for patients in cardiogenic shock, with a 1B recommendation.

Moreover, despite missing statistical significance, hard clinical end points were lower in the IABC arm, Dr. Huber said.

At 6 months, three patients in the IABC plus PCI group had died vs. nine in the PCI-alone group (P = .12).

An exploratory composite end point of time to death, shock, or new or worsening heart failure also favored the counterpulsation therapy plus PCI group over the PCI-alone group (8 events vs. 21 events, P = .03).

There was, however, a nonsignificant increase in side effects, particularly vascular complications, Dr. Huber said.

At 30 days, major vascular complications occurred in seven patients in the IABC plus PCI group vs. only two in the PCI-alone group (P = .09.). Major bleeding or transfusion occurred in five patients vs. three patients, respectively, Dr. Patel reported.

Dr. Huber said other studies are needed to define which patients might benefit from IABC. He highlighted the only other prospective trial of IACP, the TACTICS trial, in which IAPC failed to offer a survival benefit when added to fibrinolysis for patients with MI who were hemodynamically unstable, but suggested a possible benefit for patients with the most severe heart failure or hypertension (J. Thromb. Thrombolysis 2005;19:33-9).

Session comoderator Dr. Christodoulos Stefanadis of Athens University Medical School said in an interview that it is still acceptable to use IACP in both stable and unstable patients, but agreed that other studies are needed to resolve the issue.

"For many years, we believe that the use of the intra-aortic pump is an effective means to reduce infarct size and to reduce the mortality rate, especially in patients with cardiogenic shock," he said.

"In unstable patients, I personally believe that the use of the intra-aortic pump remains effective, but the question is what happens in stable patients without low blood pressure or shock."

At baseline, CRISP-AMI patients were hemodynamically stable, with a median systolic blood pressure of 130 mm Hg in the IABC plus PCI group and 135 mm Hg in the PCI-alone patients.

The time required to insert the intra-aortic balloon added just 9 minutes to the procedure, making it unlikely that this derailed the potential benefits of counterpulsation therapy, Dr. Patel said in an interview.

The results of CRISP-AMI were simultaneously published online by JAMA (2011 Aug. 30 [doi:10.1001/jama.2011.1280]).

Dr. Patel reported receiving grant funding and travel reimbursement from the study sponsor Maquet (formerly Datascope).

PARIS – Although female sex is a risk factor for worse outcomes after conventional cardiac surgery, the opposite appears to be true following transcatheter aortic valve implantation.

Among 260 consecutive patients undergoing TAVI for severe, symptomatic aortic stenosis, female sex was associated with significantly better 1-year survival (76% vs. 65%).

The study, described as the first analysis of sex difference with this emerging technique, also identified female sex as an independent predictor of long-term survival, lead author Dr. Kentaro Hayashida and his colleagues reported at the annual congress of the European Society of Cardiology.

The increased survival rate among women who were treated with TAVI may represent a paradox in the cardiovascular disease gender gap.

"Surgical aortic valve replacement in female patients is technically demanding because of their smaller stature and body surface area, higher body mass index, and smaller aortic root," Dr. Hayashida of the Institut Cardiovasculaire Paris-Sud (ICPS) in Massy, France, said in an interview. "In our study cohort, TAVI was performed with a similar device success rate, compared to males, because of the procedural feasibility inherent in this novel technique, despite the specific characteristics associated" with female sex.

TAVI was successfully achieved in 91% of women and 88.4% of men, a nonsignificant difference. Similarly, no significant sex differences were observed for 30-day mortality (12% for women and 18% for men).

Longer life expectancy and early detection of aortic stenosis in women may, in part, have contributed to their improved survival, coauthor and colleague Dr. Philippe Garot said. He pointed out that despite both sexes having made gains in cardiovascular disease mortality from 1950 to 1999, an 80-year-old man in France can expect to live 8.3 more years, compared with 10.5 additional years for an 80-year-old French woman.

The average age at the time of surgery was 83 years in both study groups.

At baseline, women had a significantly lower logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) (22% vs. 26%), higher left ventricular ejection fraction (54% vs. 47%) and less coronary artery disease (49% vs. 79%), peripheral artery disease (27% vs. 40%) and previous cardiac surgery (14% vs. 26.4%) than did men.

Women, however, also had a significantly smaller femoral artery size (7.74 mm vs. 8.55 mm), annulus size (20.9 mm vs. 22.9 mm) and valve size (23.9 mm vs. 26.3 mm) than did men, Dr. Garot said.

TAVI is emerging as the standard of care for patients with severe aortic stenosis who cannot undergo surgery, after the procedure demonstrated similar 1-year survival rates as did conventional aortic valve replacement among older, high-risk patients in the recent PARTNER (Placement of Aortic Transcatheter Valve) trial (N. Engl. J. Med. 2010;363;1597-607). A preliminary subgroup analysis suggested a benefit with the less-invasive TAVR among women and in those without prior coronary artery bypass surgery.

In a multivariate analysis of the current cohort, male sex was identified as an independent predictor of long-term mortality (odds ratio, 1.80), the authors reported. Other significant risk factors were previous cardiac surgery (OR, 2.3), postprocedural aortic regurgitation (OR, 2.3), transfusion of four or more units (OR, 2.5), acute kidney injury (OR, 6.9), and conversion to open surgery (OR, 5.1).

Notably, vascular complications were not associated with mortality in the study, Dr. Garot said.

Based on the current results, Dr. Hayashida said it seems too early to conclude that TAVI should be routinely recommended in women who are not at high risk for conventional surgery.

"After confirmation by other studies of larger patient populations in the future, maybe we can say ‘yes,’ " he added.

Data were prospectively collected on 131 women and 129 men with severe aortic stenosis who were treated at the ICPS from September 2006 through December 2010. TAVI was performed using the Edwards Sapien or Sapien XT valves (85%) or the third-generation CoreValve Revalving system (15%), with 65% of valves placed via the transfemoral approach.

Dr. Hayashida and his coauthors report no conflicts.

PARIS – Although female sex is a risk factor for worse outcomes after conventional cardiac surgery, the opposite appears to be true following transcatheter aortic valve implantation.

Among 260 consecutive patients undergoing TAVI for severe, symptomatic aortic stenosis, female sex was associated with significantly better 1-year survival (76% vs. 65%).

The study, described as the first analysis of sex difference with this emerging technique, also identified female sex as an independent predictor of long-term survival, lead author Dr. Kentaro Hayashida and his colleagues reported at the annual congress of the European Society of Cardiology.

The increased survival rate among women who were treated with TAVI may represent a paradox in the cardiovascular disease gender gap.

"Surgical aortic valve replacement in female patients is technically demanding because of their smaller stature and body surface area, higher body mass index, and smaller aortic root," Dr. Hayashida of the Institut Cardiovasculaire Paris-Sud (ICPS) in Massy, France, said in an interview. "In our study cohort, TAVI was performed with a similar device success rate, compared to males, because of the procedural feasibility inherent in this novel technique, despite the specific characteristics associated" with female sex.

TAVI was successfully achieved in 91% of women and 88.4% of men, a nonsignificant difference. Similarly, no significant sex differences were observed for 30-day mortality (12% for women and 18% for men).

Longer life expectancy and early detection of aortic stenosis in women may, in part, have contributed to their improved survival, coauthor and colleague Dr. Philippe Garot said. He pointed out that despite both sexes having made gains in cardiovascular disease mortality from 1950 to 1999, an 80-year-old man in France can expect to live 8.3 more years, compared with 10.5 additional years for an 80-year-old French woman.

The average age at the time of surgery was 83 years in both study groups.

At baseline, women had a significantly lower logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) (22% vs. 26%), higher left ventricular ejection fraction (54% vs. 47%) and less coronary artery disease (49% vs. 79%), peripheral artery disease (27% vs. 40%) and previous cardiac surgery (14% vs. 26.4%) than did men.

Women, however, also had a significantly smaller femoral artery size (7.74 mm vs. 8.55 mm), annulus size (20.9 mm vs. 22.9 mm) and valve size (23.9 mm vs. 26.3 mm) than did men, Dr. Garot said.

TAVI is emerging as the standard of care for patients with severe aortic stenosis who cannot undergo surgery, after the procedure demonstrated similar 1-year survival rates as did conventional aortic valve replacement among older, high-risk patients in the recent PARTNER (Placement of Aortic Transcatheter Valve) trial (N. Engl. J. Med. 2010;363;1597-607). A preliminary subgroup analysis suggested a benefit with the less-invasive TAVR among women and in those without prior coronary artery bypass surgery.

In a multivariate analysis of the current cohort, male sex was identified as an independent predictor of long-term mortality (odds ratio, 1.80), the authors reported. Other significant risk factors were previous cardiac surgery (OR, 2.3), postprocedural aortic regurgitation (OR, 2.3), transfusion of four or more units (OR, 2.5), acute kidney injury (OR, 6.9), and conversion to open surgery (OR, 5.1).

Notably, vascular complications were not associated with mortality in the study, Dr. Garot said.

Based on the current results, Dr. Hayashida said it seems too early to conclude that TAVI should be routinely recommended in women who are not at high risk for conventional surgery.

"After confirmation by other studies of larger patient populations in the future, maybe we can say ‘yes,’ " he added.

Data were prospectively collected on 131 women and 129 men with severe aortic stenosis who were treated at the ICPS from September 2006 through December 2010. TAVI was performed using the Edwards Sapien or Sapien XT valves (85%) or the third-generation CoreValve Revalving system (15%), with 65% of valves placed via the transfemoral approach.

Dr. Hayashida and his coauthors report no conflicts.

PARIS – Although female sex is a risk factor for worse outcomes after conventional cardiac surgery, the opposite appears to be true following transcatheter aortic valve implantation.

Among 260 consecutive patients undergoing TAVI for severe, symptomatic aortic stenosis, female sex was associated with significantly better 1-year survival (76% vs. 65%).

The study, described as the first analysis of sex difference with this emerging technique, also identified female sex as an independent predictor of long-term survival, lead author Dr. Kentaro Hayashida and his colleagues reported at the annual congress of the European Society of Cardiology.

The increased survival rate among women who were treated with TAVI may represent a paradox in the cardiovascular disease gender gap.

"Surgical aortic valve replacement in female patients is technically demanding because of their smaller stature and body surface area, higher body mass index, and smaller aortic root," Dr. Hayashida of the Institut Cardiovasculaire Paris-Sud (ICPS) in Massy, France, said in an interview. "In our study cohort, TAVI was performed with a similar device success rate, compared to males, because of the procedural feasibility inherent in this novel technique, despite the specific characteristics associated" with female sex.

TAVI was successfully achieved in 91% of women and 88.4% of men, a nonsignificant difference. Similarly, no significant sex differences were observed for 30-day mortality (12% for women and 18% for men).

Longer life expectancy and early detection of aortic stenosis in women may, in part, have contributed to their improved survival, coauthor and colleague Dr. Philippe Garot said. He pointed out that despite both sexes having made gains in cardiovascular disease mortality from 1950 to 1999, an 80-year-old man in France can expect to live 8.3 more years, compared with 10.5 additional years for an 80-year-old French woman.

The average age at the time of surgery was 83 years in both study groups.

At baseline, women had a significantly lower logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) (22% vs. 26%), higher left ventricular ejection fraction (54% vs. 47%) and less coronary artery disease (49% vs. 79%), peripheral artery disease (27% vs. 40%) and previous cardiac surgery (14% vs. 26.4%) than did men.

Women, however, also had a significantly smaller femoral artery size (7.74 mm vs. 8.55 mm), annulus size (20.9 mm vs. 22.9 mm) and valve size (23.9 mm vs. 26.3 mm) than did men, Dr. Garot said.

TAVI is emerging as the standard of care for patients with severe aortic stenosis who cannot undergo surgery, after the procedure demonstrated similar 1-year survival rates as did conventional aortic valve replacement among older, high-risk patients in the recent PARTNER (Placement of Aortic Transcatheter Valve) trial (N. Engl. J. Med. 2010;363;1597-607). A preliminary subgroup analysis suggested a benefit with the less-invasive TAVR among women and in those without prior coronary artery bypass surgery.

In a multivariate analysis of the current cohort, male sex was identified as an independent predictor of long-term mortality (odds ratio, 1.80), the authors reported. Other significant risk factors were previous cardiac surgery (OR, 2.3), postprocedural aortic regurgitation (OR, 2.3), transfusion of four or more units (OR, 2.5), acute kidney injury (OR, 6.9), and conversion to open surgery (OR, 5.1).

Notably, vascular complications were not associated with mortality in the study, Dr. Garot said.

Based on the current results, Dr. Hayashida said it seems too early to conclude that TAVI should be routinely recommended in women who are not at high risk for conventional surgery.

"After confirmation by other studies of larger patient populations in the future, maybe we can say ‘yes,’ " he added.

Data were prospectively collected on 131 women and 129 men with severe aortic stenosis who were treated at the ICPS from September 2006 through December 2010. TAVI was performed using the Edwards Sapien or Sapien XT valves (85%) or the third-generation CoreValve Revalving system (15%), with 65% of valves placed via the transfemoral approach.

Dr. Hayashida and his coauthors report no conflicts.

PARIS – Results of two randomized controlled trials appear to solidify the safety of remote monitoring of implantable cardioverter defibrillators, and one of the studies showed a significant decrease in the number of patients receiving inappropriate shocks in the remote-monitoring group.

Manufacturers of ICDs currently recommend in-clinic follow-up every 3 months to detect clinical events or device malfunctions. With increasing numbers of people receiving ICDs to prevent sudden cardiac death from rhythm disturbances, investigators are testing ways to avoid the time constraints of so many in-clinic visits by remotely transmitting information from the device via telephone from the patient’s home. Most ICDs now have this capability.

The two randomized controlled trials support findings from patient registries in Europe and in the United States, where remote monitoring is common.

In the yearlong Evaluation of Tele Follow-up (EVATEL) trial, 1,501 patients at 30 French centers were randomized to in-clinic follow-up at the implant center every 3 months or to remote transmission of data to the implant center every 3 months. The study included four types of ICDs.

Results showed no significant difference between groups in the time to first major cardiovascular event or in the rates of major cardiovascular events (death from all causes, cardiovascular-related hospitalization, or inappropriate or ineffective shocks), Dr. Philippe Mabo and his associates reported at the annual congress of the European Society of Cardiology .

Rates of this composite end point were 28% in the remote-monitoring group and 29% in the control group in an intent-to-treat analysis, showing that home monitoring was not inferior to in-office monitoring. In a per-protocol analysis, the primary end points were seen in 28% and 30% of the groups, respectively, but the confidence interval was too wide to claim that there was no significant difference between groups, said Dr. Mabo of Rennes (France) University Hospital.

The trial could not demonstrate an impact on preventing major clinical events, but it did reinforce the safety of remote monitoring, he said.

The study also found a significant 27% reduction in the number of inappropriate shocks delivered by the ICDs, from approximately 8% in the control group to 5% in the remote-monitoring group.

Among several weaknesses of the study, there were no interventions planned in response to monitoring, said Dr. Angelo Auricchio, who commented on the study in the presentation session. Using the data to intervene in problems with ICDs is "the greatest advantage" of the technology, so it is not surprising that the EVATEL study did not show a major impact on cardiovascular end points, said Dr. Auricchio of the Fondazione Cardiocentro Ticino, Lugano, Switzerland.

In addition, the number of patients in the study did not quite reach the calculated sample size required to demonstrate noninferiority of home ICD monitoring.

The separate Effectiveness and Cost of ICD Follow-up Schedule with Telecardiology (ECOST) study randomized 433 patients in 43 French centers to daily remote monitoring using the Biotronik Home Monitoring system or quarterly in-clinic follow-up for 27 months.

Rates of a combined end point of mortality, major cardiovascular events, or major device-related adverse events did not differ significantly between groups, affecting 38% of the remote-monitoring group and 42% of the control group, Dr. Salem Kacet and his associates reported.

Among secondary outcomes, the remote monitoring group showed a significant 52% reduction in the number of patients receiving inappropriate shocks (5% in the remote-monitoring group and 10% in the control group), said Dr. Kacet of the University of Lille, France.

The number of patients hospitalized because of inappropriate shocks also was significantly lower in the remote-monitoring group (3) compared with the control group (11).

A significant 76% decrease in the total number of charged shocks in the remote-monitoring group (499 shocks), compared with the control group (2,081 shocks) translated into a significant impact on battery longevity. Among patients with more than one charged shock during the study, ICD battery capacity depleted 0.07% per day in the remote-monitoring group and 0.18% per day in the control group, so that 3 patients in the remote-monitoring group and 11 in the control group had ICDs left with less than 50% of battery capacity.

The number of delivered shocks was significantly lower in the remote-monitoring group (193) than in the control group (657), a significant 71% difference.

Quality-of-life scores on the Short Form-36 were similar between groups.

The relatively long-term follow-up of the ECOST study supports the safety and noninferiority of remote monitoring of ICDs, and shows that home monitoring could reduce inappropriate shocks, charged shocks and delivered shocks, thus prolonging battery longevity and potentially delaying the need for battery replacement surgery, as well as decreasing associated risks.

"This is a very important observation," said Dr. Sidney Goldstein of Henry Ford Hospital, Detroit, who co-moderated a press briefing that included the two studies.

Dr. Kacet said the investigators will perform a secondary analysis of costs in the two monitoring groups soon. The cost analysis is important, because it is not known if the cost of resources to analyze the increased data from home monitoring outweighs potential financial benefits from reduced shocks and prolonged battery life, Dr. Gordon F. Tomaselli said in an interview.

U.S. patients with ICDs often have more than one doctor managing their care. If home monitoring can eliminate some visits to their primary care doctor, cardiologist, or electrophysiologist, this could make an important difference in convenience and costs, said Dr. Tomaselli, president of the American Heart Association and chief of cardiology at Johns Hopkins University, Baltimore.

"We use remote monitoring now for people who find it difficult to get back to our arrhythmia center to be evaluated. I don’t think [these studies] will change things too much in the way of what we do," he said. "For people who are very close, it’s oftentimes not inconvenient for them to come see us face-to-face."

The studies also add to evidence from two previous randomized controlled trials that relied on surrogate end points to evaluate remote ICD monitoring. One study of 1,339 patients reported a 45% reduction in in-office device evaluations among remotely monitored patients without affecting safety (Circulation 2010;122:325-32). A separate study of 1,997 patients found that remote monitoring reduced the time from an ICD-related event to a clinical decision from 22 days to 5 days, and reduced the length of cardiovascular-related hospital stays from an average of 4.0 days to 3.3 days (J. Am. Coll. Cardiol. 2011;57:1181-9).

Biotronik funded the ECOST study. Dr. Kacet has received research funding from Biotronik, Boston Scientific, Medtronic, Saint Jude Medical, Sorin Group, Bayer, Boehringer-Ingelheim, Meda, and Sanofi-Aventis. Dr. Mabo has been a speaker, consultant, or investigator for all five companies making implantable cardiac devices. Dr. Auricchio has been a consultant to all companies making implantable cardiac devices. Dr. Tomaselli said he has no conflicts of interest.

PARIS – Results of two randomized controlled trials appear to solidify the safety of remote monitoring of implantable cardioverter defibrillators, and one of the studies showed a significant decrease in the number of patients receiving inappropriate shocks in the remote-monitoring group.

Manufacturers of ICDs currently recommend in-clinic follow-up every 3 months to detect clinical events or device malfunctions. With increasing numbers of people receiving ICDs to prevent sudden cardiac death from rhythm disturbances, investigators are testing ways to avoid the time constraints of so many in-clinic visits by remotely transmitting information from the device via telephone from the patient’s home. Most ICDs now have this capability.

The two randomized controlled trials support findings from patient registries in Europe and in the United States, where remote monitoring is common.

In the yearlong Evaluation of Tele Follow-up (EVATEL) trial, 1,501 patients at 30 French centers were randomized to in-clinic follow-up at the implant center every 3 months or to remote transmission of data to the implant center every 3 months. The study included four types of ICDs.

Results showed no significant difference between groups in the time to first major cardiovascular event or in the rates of major cardiovascular events (death from all causes, cardiovascular-related hospitalization, or inappropriate or ineffective shocks), Dr. Philippe Mabo and his associates reported at the annual congress of the European Society of Cardiology .

Rates of this composite end point were 28% in the remote-monitoring group and 29% in the control group in an intent-to-treat analysis, showing that home monitoring was not inferior to in-office monitoring. In a per-protocol analysis, the primary end points were seen in 28% and 30% of the groups, respectively, but the confidence interval was too wide to claim that there was no significant difference between groups, said Dr. Mabo of Rennes (France) University Hospital.

The trial could not demonstrate an impact on preventing major clinical events, but it did reinforce the safety of remote monitoring, he said.

The study also found a significant 27% reduction in the number of inappropriate shocks delivered by the ICDs, from approximately 8% in the control group to 5% in the remote-monitoring group.

Among several weaknesses of the study, there were no interventions planned in response to monitoring, said Dr. Angelo Auricchio, who commented on the study in the presentation session. Using the data to intervene in problems with ICDs is "the greatest advantage" of the technology, so it is not surprising that the EVATEL study did not show a major impact on cardiovascular end points, said Dr. Auricchio of the Fondazione Cardiocentro Ticino, Lugano, Switzerland.

In addition, the number of patients in the study did not quite reach the calculated sample size required to demonstrate noninferiority of home ICD monitoring.

The separate Effectiveness and Cost of ICD Follow-up Schedule with Telecardiology (ECOST) study randomized 433 patients in 43 French centers to daily remote monitoring using the Biotronik Home Monitoring system or quarterly in-clinic follow-up for 27 months.

Rates of a combined end point of mortality, major cardiovascular events, or major device-related adverse events did not differ significantly between groups, affecting 38% of the remote-monitoring group and 42% of the control group, Dr. Salem Kacet and his associates reported.

Among secondary outcomes, the remote monitoring group showed a significant 52% reduction in the number of patients receiving inappropriate shocks (5% in the remote-monitoring group and 10% in the control group), said Dr. Kacet of the University of Lille, France.

The number of patients hospitalized because of inappropriate shocks also was significantly lower in the remote-monitoring group (3) compared with the control group (11).

A significant 76% decrease in the total number of charged shocks in the remote-monitoring group (499 shocks), compared with the control group (2,081 shocks) translated into a significant impact on battery longevity. Among patients with more than one charged shock during the study, ICD battery capacity depleted 0.07% per day in the remote-monitoring group and 0.18% per day in the control group, so that 3 patients in the remote-monitoring group and 11 in the control group had ICDs left with less than 50% of battery capacity.

The number of delivered shocks was significantly lower in the remote-monitoring group (193) than in the control group (657), a significant 71% difference.

Quality-of-life scores on the Short Form-36 were similar between groups.

The relatively long-term follow-up of the ECOST study supports the safety and noninferiority of remote monitoring of ICDs, and shows that home monitoring could reduce inappropriate shocks, charged shocks and delivered shocks, thus prolonging battery longevity and potentially delaying the need for battery replacement surgery, as well as decreasing associated risks.

"This is a very important observation," said Dr. Sidney Goldstein of Henry Ford Hospital, Detroit, who co-moderated a press briefing that included the two studies.

Dr. Kacet said the investigators will perform a secondary analysis of costs in the two monitoring groups soon. The cost analysis is important, because it is not known if the cost of resources to analyze the increased data from home monitoring outweighs potential financial benefits from reduced shocks and prolonged battery life, Dr. Gordon F. Tomaselli said in an interview.

U.S. patients with ICDs often have more than one doctor managing their care. If home monitoring can eliminate some visits to their primary care doctor, cardiologist, or electrophysiologist, this could make an important difference in convenience and costs, said Dr. Tomaselli, president of the American Heart Association and chief of cardiology at Johns Hopkins University, Baltimore.

"We use remote monitoring now for people who find it difficult to get back to our arrhythmia center to be evaluated. I don’t think [these studies] will change things too much in the way of what we do," he said. "For people who are very close, it’s oftentimes not inconvenient for them to come see us face-to-face."

The studies also add to evidence from two previous randomized controlled trials that relied on surrogate end points to evaluate remote ICD monitoring. One study of 1,339 patients reported a 45% reduction in in-office device evaluations among remotely monitored patients without affecting safety (Circulation 2010;122:325-32). A separate study of 1,997 patients found that remote monitoring reduced the time from an ICD-related event to a clinical decision from 22 days to 5 days, and reduced the length of cardiovascular-related hospital stays from an average of 4.0 days to 3.3 days (J. Am. Coll. Cardiol. 2011;57:1181-9).

Biotronik funded the ECOST study. Dr. Kacet has received research funding from Biotronik, Boston Scientific, Medtronic, Saint Jude Medical, Sorin Group, Bayer, Boehringer-Ingelheim, Meda, and Sanofi-Aventis. Dr. Mabo has been a speaker, consultant, or investigator for all five companies making implantable cardiac devices. Dr. Auricchio has been a consultant to all companies making implantable cardiac devices. Dr. Tomaselli said he has no conflicts of interest.

PARIS – Results of two randomized controlled trials appear to solidify the safety of remote monitoring of implantable cardioverter defibrillators, and one of the studies showed a significant decrease in the number of patients receiving inappropriate shocks in the remote-monitoring group.

Manufacturers of ICDs currently recommend in-clinic follow-up every 3 months to detect clinical events or device malfunctions. With increasing numbers of people receiving ICDs to prevent sudden cardiac death from rhythm disturbances, investigators are testing ways to avoid the time constraints of so many in-clinic visits by remotely transmitting information from the device via telephone from the patient’s home. Most ICDs now have this capability.

The two randomized controlled trials support findings from patient registries in Europe and in the United States, where remote monitoring is common.

In the yearlong Evaluation of Tele Follow-up (EVATEL) trial, 1,501 patients at 30 French centers were randomized to in-clinic follow-up at the implant center every 3 months or to remote transmission of data to the implant center every 3 months. The study included four types of ICDs.

Results showed no significant difference between groups in the time to first major cardiovascular event or in the rates of major cardiovascular events (death from all causes, cardiovascular-related hospitalization, or inappropriate or ineffective shocks), Dr. Philippe Mabo and his associates reported at the annual congress of the European Society of Cardiology .

Rates of this composite end point were 28% in the remote-monitoring group and 29% in the control group in an intent-to-treat analysis, showing that home monitoring was not inferior to in-office monitoring. In a per-protocol analysis, the primary end points were seen in 28% and 30% of the groups, respectively, but the confidence interval was too wide to claim that there was no significant difference between groups, said Dr. Mabo of Rennes (France) University Hospital.

The trial could not demonstrate an impact on preventing major clinical events, but it did reinforce the safety of remote monitoring, he said.

The study also found a significant 27% reduction in the number of inappropriate shocks delivered by the ICDs, from approximately 8% in the control group to 5% in the remote-monitoring group.

Among several weaknesses of the study, there were no interventions planned in response to monitoring, said Dr. Angelo Auricchio, who commented on the study in the presentation session. Using the data to intervene in problems with ICDs is "the greatest advantage" of the technology, so it is not surprising that the EVATEL study did not show a major impact on cardiovascular end points, said Dr. Auricchio of the Fondazione Cardiocentro Ticino, Lugano, Switzerland.

In addition, the number of patients in the study did not quite reach the calculated sample size required to demonstrate noninferiority of home ICD monitoring.

The separate Effectiveness and Cost of ICD Follow-up Schedule with Telecardiology (ECOST) study randomized 433 patients in 43 French centers to daily remote monitoring using the Biotronik Home Monitoring system or quarterly in-clinic follow-up for 27 months.

Rates of a combined end point of mortality, major cardiovascular events, or major device-related adverse events did not differ significantly between groups, affecting 38% of the remote-monitoring group and 42% of the control group, Dr. Salem Kacet and his associates reported.

Among secondary outcomes, the remote monitoring group showed a significant 52% reduction in the number of patients receiving inappropriate shocks (5% in the remote-monitoring group and 10% in the control group), said Dr. Kacet of the University of Lille, France.

The number of patients hospitalized because of inappropriate shocks also was significantly lower in the remote-monitoring group (3) compared with the control group (11).

A significant 76% decrease in the total number of charged shocks in the remote-monitoring group (499 shocks), compared with the control group (2,081 shocks) translated into a significant impact on battery longevity. Among patients with more than one charged shock during the study, ICD battery capacity depleted 0.07% per day in the remote-monitoring group and 0.18% per day in the control group, so that 3 patients in the remote-monitoring group and 11 in the control group had ICDs left with less than 50% of battery capacity.

The number of delivered shocks was significantly lower in the remote-monitoring group (193) than in the control group (657), a significant 71% difference.

Quality-of-life scores on the Short Form-36 were similar between groups.

The relatively long-term follow-up of the ECOST study supports the safety and noninferiority of remote monitoring of ICDs, and shows that home monitoring could reduce inappropriate shocks, charged shocks and delivered shocks, thus prolonging battery longevity and potentially delaying the need for battery replacement surgery, as well as decreasing associated risks.

"This is a very important observation," said Dr. Sidney Goldstein of Henry Ford Hospital, Detroit, who co-moderated a press briefing that included the two studies.

Dr. Kacet said the investigators will perform a secondary analysis of costs in the two monitoring groups soon. The cost analysis is important, because it is not known if the cost of resources to analyze the increased data from home monitoring outweighs potential financial benefits from reduced shocks and prolonged battery life, Dr. Gordon F. Tomaselli said in an interview.

U.S. patients with ICDs often have more than one doctor managing their care. If home monitoring can eliminate some visits to their primary care doctor, cardiologist, or electrophysiologist, this could make an important difference in convenience and costs, said Dr. Tomaselli, president of the American Heart Association and chief of cardiology at Johns Hopkins University, Baltimore.

"We use remote monitoring now for people who find it difficult to get back to our arrhythmia center to be evaluated. I don’t think [these studies] will change things too much in the way of what we do," he said. "For people who are very close, it’s oftentimes not inconvenient for them to come see us face-to-face."

The studies also add to evidence from two previous randomized controlled trials that relied on surrogate end points to evaluate remote ICD monitoring. One study of 1,339 patients reported a 45% reduction in in-office device evaluations among remotely monitored patients without affecting safety (Circulation 2010;122:325-32). A separate study of 1,997 patients found that remote monitoring reduced the time from an ICD-related event to a clinical decision from 22 days to 5 days, and reduced the length of cardiovascular-related hospital stays from an average of 4.0 days to 3.3 days (J. Am. Coll. Cardiol. 2011;57:1181-9).

Biotronik funded the ECOST study. Dr. Kacet has received research funding from Biotronik, Boston Scientific, Medtronic, Saint Jude Medical, Sorin Group, Bayer, Boehringer-Ingelheim, Meda, and Sanofi-Aventis. Dr. Mabo has been a speaker, consultant, or investigator for all five companies making implantable cardiac devices. Dr. Auricchio has been a consultant to all companies making implantable cardiac devices. Dr. Tomaselli said he has no conflicts of interest.

PARIS – The aldosterone antagonist eplerenone cut cardiovascular events and the need for hospitalization significantly across all risk levels in patients with mild heart failure, according to a subanalysis of the EMPHASIS-HF trial.

Eplerenone (Inspra) was also shown to trim troublesome and costly repeat heart failure hospitalizations in a subset of patients followed for up to 10 additional months after the pivotal, phase III trial closed, Dr. Bertram Pitt reported at the annual congress of the European Society of Cardiology.

"Overall efficacy, no matter where we looked, was about the same, and we had the same safety," he told reporters.

EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) was stopped prematurely last spring after eplerenone in addition to standard therapy demonstrated a 37% (hazard ratio, 0.63) improvement over placebo in the primary end point of death from cardiovascular causes or heart failure hospitalization in 2,637 patients with mild New York Heart Association class II systolic heart failure (N. Engl. J. Med. 2011;364:11-21).

Among 1,597 patients who remained on double-blind therapy after study closure, the primary end point occurred in 21% on eplerenone and 29% on placebo (HR, 0.66, P value less than .0001), said Dr. Pitt, with the University of Michigan, Ann Arbor.

Repeat hospitalization for heart failure was significantly reduced with eplerenone (rate ratio, 0.62, P less than .001).

"This suggests, to us at least, that this is going to have important cost implications, quality of life implications, as well as important implications on survival, since we know that heart failure hospitalization relates to target-organ damage and survival," he said.

The benefits of eplerenone were particularly compelling in elderly patients and those with diabetes and renal dysfunction, three high-risk populations in whom clinicians are hesitant to use adjuvant aldosterone blockade because of fears of inducing hyperkalemia, Dr. Pitt said. He pointed out that recent head-to-head data show that the aldosterone antagonist spironolactone (Aldactone) raises hemoglobin A_1C and cortisol levels and reduces adiponectin in patients with diabetes, whereas eplerenone does not.

When Dr. Pitt and colleagues looked at patients with diabetes in the subanalysis, the benefit was better than that observed in the overall EMPHASIS-HF cohort, with a 46% reduction in the primary end point (HR, 0.54, P value less than .0001).

Dr. Pitt noted that the current American Heart Association, American College of Cardiology and European guidelines for aldosterone blockade don’t specify a particular agent, but look at the agents as a class.

"We believe with [these] data, that in the next guidelines there should at least be some consideration for the specific use of eplerenone, at least in the subset of patients with diabetes," he said.

Among patients with an estimated glomerular filtration rate less than 60 mL per minute per 1.73 m², the improvement in the primary outcome reached 38% with eplerenone over placebo (HR, 0.62, P = .0001).

The study excluded patients with a baseline serum potassium level above 5.0 mmol/L and estimated GFR below 30 mL per minute per 1.73 m² in an attempt to minimize the risk of hyperkalemia. Despite this, the positive results remain applicable, Dr. Pitt said in an interview.

Among elderly patients at least 75 years old, the benefit on the primary end point with eplerenone reached 34% (HR, 0.66, P = .004).

Significant benefits were also observed in patients with a left ventricular ejection fraction less than 30% (HR, 0.65, P less than .0001) and with a median systolic blood pressure less than 123 mmHg (HR, 0.63, P less than .0001).

As seen in the overall EMPHASIS-HF cohort, the benefits of eplerenone were accompanied by a significant increase in the incidence of serum potassium more than 5.5 mmol/L in each of the high-risk subgroups.

There were, however, no significant increases in the incidence of serum potassium more than 6 mmol/L, hospitalization leading to treatment discontinuation, hospitalization for/or deaths due to hyperkalemia, or hospitalizations for worsening renal function, Dr. Pitt said.

Invited discussant Dr. Piotr Ponikowski, with the 4th Military Hospital in Wroclaw, Poland, highlighted as important the benefits of eplerenone in people with diabetes and the reduction in repeat hospitalizations. He noted that up to 50% of heart failure patients are rehospitalized and these visits are associated with significant costs and reduced quality of life and mortality. Still, aldosterone antagonists remain underutilized in heart failure patients in Europe as well as the United States.

Physicians frequently question whether clinical trial data are real, consistent, and clinically meaningful, he said. "With the presented data, we can now say that the answer to all these questions is ‘yes.’ "

Pfizer sponsored the trial. Dr. Pitt reports financial relationships with several firms excluding Pfizer. His coauthors report similar relationships including employment with Pfizer.

PARIS – The aldosterone antagonist eplerenone cut cardiovascular events and the need for hospitalization significantly across all risk levels in patients with mild heart failure, according to a subanalysis of the EMPHASIS-HF trial.

Eplerenone (Inspra) was also shown to trim troublesome and costly repeat heart failure hospitalizations in a subset of patients followed for up to 10 additional months after the pivotal, phase III trial closed, Dr. Bertram Pitt reported at the annual congress of the European Society of Cardiology.

"Overall efficacy, no matter where we looked, was about the same, and we had the same safety," he told reporters.

EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) was stopped prematurely last spring after eplerenone in addition to standard therapy demonstrated a 37% (hazard ratio, 0.63) improvement over placebo in the primary end point of death from cardiovascular causes or heart failure hospitalization in 2,637 patients with mild New York Heart Association class II systolic heart failure (N. Engl. J. Med. 2011;364:11-21).

Among 1,597 patients who remained on double-blind therapy after study closure, the primary end point occurred in 21% on eplerenone and 29% on placebo (HR, 0.66, P value less than .0001), said Dr. Pitt, with the University of Michigan, Ann Arbor.

Repeat hospitalization for heart failure was significantly reduced with eplerenone (rate ratio, 0.62, P less than .001).

"This suggests, to us at least, that this is going to have important cost implications, quality of life implications, as well as important implications on survival, since we know that heart failure hospitalization relates to target-organ damage and survival," he said.

The benefits of eplerenone were particularly compelling in elderly patients and those with diabetes and renal dysfunction, three high-risk populations in whom clinicians are hesitant to use adjuvant aldosterone blockade because of fears of inducing hyperkalemia, Dr. Pitt said. He pointed out that recent head-to-head data show that the aldosterone antagonist spironolactone (Aldactone) raises hemoglobin A_1C and cortisol levels and reduces adiponectin in patients with diabetes, whereas eplerenone does not.

When Dr. Pitt and colleagues looked at patients with diabetes in the subanalysis, the benefit was better than that observed in the overall EMPHASIS-HF cohort, with a 46% reduction in the primary end point (HR, 0.54, P value less than .0001).

Dr. Pitt noted that the current American Heart Association, American College of Cardiology and European guidelines for aldosterone blockade don’t specify a particular agent, but look at the agents as a class.

"We believe with [these] data, that in the next guidelines there should at least be some consideration for the specific use of eplerenone, at least in the subset of patients with diabetes," he said.

Among patients with an estimated glomerular filtration rate less than 60 mL per minute per 1.73 m², the improvement in the primary outcome reached 38% with eplerenone over placebo (HR, 0.62, P = .0001).

The study excluded patients with a baseline serum potassium level above 5.0 mmol/L and estimated GFR below 30 mL per minute per 1.73 m² in an attempt to minimize the risk of hyperkalemia. Despite this, the positive results remain applicable, Dr. Pitt said in an interview.

Among elderly patients at least 75 years old, the benefit on the primary end point with eplerenone reached 34% (HR, 0.66, P = .004).

Significant benefits were also observed in patients with a left ventricular ejection fraction less than 30% (HR, 0.65, P less than .0001) and with a median systolic blood pressure less than 123 mmHg (HR, 0.63, P less than .0001).

As seen in the overall EMPHASIS-HF cohort, the benefits of eplerenone were accompanied by a significant increase in the incidence of serum potassium more than 5.5 mmol/L in each of the high-risk subgroups.

There were, however, no significant increases in the incidence of serum potassium more than 6 mmol/L, hospitalization leading to treatment discontinuation, hospitalization for/or deaths due to hyperkalemia, or hospitalizations for worsening renal function, Dr. Pitt said.

Invited discussant Dr. Piotr Ponikowski, with the 4th Military Hospital in Wroclaw, Poland, highlighted as important the benefits of eplerenone in people with diabetes and the reduction in repeat hospitalizations. He noted that up to 50% of heart failure patients are rehospitalized and these visits are associated with significant costs and reduced quality of life and mortality. Still, aldosterone antagonists remain underutilized in heart failure patients in Europe as well as the United States.

Physicians frequently question whether clinical trial data are real, consistent, and clinically meaningful, he said. "With the presented data, we can now say that the answer to all these questions is ‘yes.’ "

Pfizer sponsored the trial. Dr. Pitt reports financial relationships with several firms excluding Pfizer. His coauthors report similar relationships including employment with Pfizer.

PARIS – The aldosterone antagonist eplerenone cut cardiovascular events and the need for hospitalization significantly across all risk levels in patients with mild heart failure, according to a subanalysis of the EMPHASIS-HF trial.

Eplerenone (Inspra) was also shown to trim troublesome and costly repeat heart failure hospitalizations in a subset of patients followed for up to 10 additional months after the pivotal, phase III trial closed, Dr. Bertram Pitt reported at the annual congress of the European Society of Cardiology.

"Overall efficacy, no matter where we looked, was about the same, and we had the same safety," he told reporters.

EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) was stopped prematurely last spring after eplerenone in addition to standard therapy demonstrated a 37% (hazard ratio, 0.63) improvement over placebo in the primary end point of death from cardiovascular causes or heart failure hospitalization in 2,637 patients with mild New York Heart Association class II systolic heart failure (N. Engl. J. Med. 2011;364:11-21).

Among 1,597 patients who remained on double-blind therapy after study closure, the primary end point occurred in 21% on eplerenone and 29% on placebo (HR, 0.66, P value less than .0001), said Dr. Pitt, with the University of Michigan, Ann Arbor.

Repeat hospitalization for heart failure was significantly reduced with eplerenone (rate ratio, 0.62, P less than .001).

"This suggests, to us at least, that this is going to have important cost implications, quality of life implications, as well as important implications on survival, since we know that heart failure hospitalization relates to target-organ damage and survival," he said.

The benefits of eplerenone were particularly compelling in elderly patients and those with diabetes and renal dysfunction, three high-risk populations in whom clinicians are hesitant to use adjuvant aldosterone blockade because of fears of inducing hyperkalemia, Dr. Pitt said. He pointed out that recent head-to-head data show that the aldosterone antagonist spironolactone (Aldactone) raises hemoglobin A_1C and cortisol levels and reduces adiponectin in patients with diabetes, whereas eplerenone does not.

When Dr. Pitt and colleagues looked at patients with diabetes in the subanalysis, the benefit was better than that observed in the overall EMPHASIS-HF cohort, with a 46% reduction in the primary end point (HR, 0.54, P value less than .0001).

Dr. Pitt noted that the current American Heart Association, American College of Cardiology and European guidelines for aldosterone blockade don’t specify a particular agent, but look at the agents as a class.

"We believe with [these] data, that in the next guidelines there should at least be some consideration for the specific use of eplerenone, at least in the subset of patients with diabetes," he said.

Among patients with an estimated glomerular filtration rate less than 60 mL per minute per 1.73 m², the improvement in the primary outcome reached 38% with eplerenone over placebo (HR, 0.62, P = .0001).

The study excluded patients with a baseline serum potassium level above 5.0 mmol/L and estimated GFR below 30 mL per minute per 1.73 m² in an attempt to minimize the risk of hyperkalemia. Despite this, the positive results remain applicable, Dr. Pitt said in an interview.

Among elderly patients at least 75 years old, the benefit on the primary end point with eplerenone reached 34% (HR, 0.66, P = .004).

Significant benefits were also observed in patients with a left ventricular ejection fraction less than 30% (HR, 0.65, P less than .0001) and with a median systolic blood pressure less than 123 mmHg (HR, 0.63, P less than .0001).

As seen in the overall EMPHASIS-HF cohort, the benefits of eplerenone were accompanied by a significant increase in the incidence of serum potassium more than 5.5 mmol/L in each of the high-risk subgroups.

There were, however, no significant increases in the incidence of serum potassium more than 6 mmol/L, hospitalization leading to treatment discontinuation, hospitalization for/or deaths due to hyperkalemia, or hospitalizations for worsening renal function, Dr. Pitt said.

Invited discussant Dr. Piotr Ponikowski, with the 4th Military Hospital in Wroclaw, Poland, highlighted as important the benefits of eplerenone in people with diabetes and the reduction in repeat hospitalizations. He noted that up to 50% of heart failure patients are rehospitalized and these visits are associated with significant costs and reduced quality of life and mortality. Still, aldosterone antagonists remain underutilized in heart failure patients in Europe as well as the United States.

Physicians frequently question whether clinical trial data are real, consistent, and clinically meaningful, he said. "With the presented data, we can now say that the answer to all these questions is ‘yes.’ "

Pfizer sponsored the trial. Dr. Pitt reports financial relationships with several firms excluding Pfizer. His coauthors report similar relationships including employment with Pfizer.

PARIS – The growing list of oral anticoagulant drugs jockeying to replace warfarin as the go-to agent for stroke prevention in patients with atrial fibrillation added a new candidate, apixaban, that appeared to immediately take the lead on the strength of strikingly impressive results in an 18,000-patient trial.

When matched against warfarin, atrial fibrillation (AF) patients treated with apixaban (Bristol-Myers Squibb, Pfizer) had significantly lower rates of stroke and systemic embolism, major bleeding complication, and overall mortality, compared with patients randomized to warfarin during a median follow-up of 1.8 years, Dr. Christopher B. Granger reported Aug. 28 at the annual congress of the European Society of Cardiology, and in a published article that concurrently appeared online (N. Engl. J. Med. 2011 Aug. 28 [10.1056/NEJMoa1107039]).

Heidi Splete/Elsevier Global Medical News

"Treatment with apixaban as compared with warfarin in patients with AF and at least one additional risk factor for stroke reduces stroke and systemic embolism by [a relative] 21%, reduces major bleeding by [a relative] 31%, and reduces mortality by [a relative] 11%," all statistically significant differences, reported Dr. Granger, director of the cardiac care unit at Duke University in Durham, N.C.

"I view the study as a home run. It is incredibly important, and it put another stake in the heart of warfarin in the management of atrial fibrillation to prevent stroke," commented Dr. Ralph Brindis, senior adviser for cardiovascular diseases at Northern California Kaiser.

Apixaban’s accomplishment in significantly surpassing warfarin’s performance for the trio of stroke prevention, bleeding safety, and overall mortality in its pivotal trial, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study, appeared to vault it ahead of dabigatran (Pradaxa, Boehringer Ingelheim), which received Food and Drug Administration approval for stroke prevention in AF patients last October, and the still-investigational agent rivaroxaban (Xarelto, Janssen), which the FDA is currently reviewing for a similar AF indication.

Neither dabigatran nor rivaroxaban could match apixaban’s performance in their respective pivotal AF trials: the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) study that matched dabigatran against warfarin in 18,113 randomized patients (N. Engl. J. Med. 2009;361:1139-51), and the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study that pitted rivaroxaban against warfarin in 14,264 randomized patients (N. Engl. J. Med. 2011 Aug. 10 [10.1056/NEJMoa1009638]).

In RE-LY, which tested two different dabigatran dosages, the 110-mg/b.i.d. dosage produced stroke and systemic embolism prevention that was noninferior to warfarin while leading to a statistically significant reduction in major bleeds, and the 150-mg/b.i.d. dosage (the primary dosage approved by the FDA) produced a statically significant reduction in strokes and systemic embolisms compared with warfarin while being noninferior to the comparator for major bleeds. In ROCKET-AF, once-daily treatment with rivaroxaban proved noninferior to warfarin for both the primary efficacy end point of fewer strokes and systemic embolisms and the safety end point of major bleeds.

"We think we hit the sweet spot in terms of the [apixaban] dose" in ARISTOTLE, said Dr. Granger, and although he and other experts warned against the pitfalls of cross-trial comparisons, many also acknowledged that mental calculations comparing the demonstrated pros and cons of each of these three new drugs are inevitable once all three drugs become routinely available.

Results from a study directly comparing two or all three of these drugs won’t be available soon, leaving it to clinicians to take into account not only the efficacy and safety performance of the three agents in these studies but other considerations as well, such as their prices, dosing convenience, adverse effects, and individual patient reactions.

"Apixaban has a certain edge because of its safety; [it] reduced all types of bleeding and had impressive tolerability," said Dr. Lars Wallentin, professor and head of cardiology research at Uppsala University in Sweden, and a coinvestigator in both the ARISTOTLE and RE-LY trials. Apixaban also has the attraction of having another major stroke-prevention in AF under its belt, the Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) study, which randomized 5,599 patients (N. Engl. J. Med. 2011;364:806-17).

"We have two [apixaban] trials [in] a large program, showing this safety. In AVERROES the bleeding risk with apixaban was the same as with low-dose aspirin," Dr. Wallentin said in an interview.

"I think it will be very competitive" among the three new drugs, said Dr. Michael D. Ezekowitz, professor of medicine at Thomas Jefferson University in Philadelphia and a lead investigator of the RE-LY trial. "That’s what we want; multiple agents competing, each one finding their niche in the huge field of atrial fibrillation treatment. The companies [that make these new drugs] will compete at multiple levels."

ARISTOTLE’s results showed that among patients randomized to apixaban, the rate of the primary stroke and systemic end point during follow-up was 1.27%, major bleeds occurred in 2.13%, the rate of death from any cause was 3.52%, and 0.24% of patients developed a hemorrhagic stroke. In patients randomized to warfarin, strokes or embolisms occurred in 1.60%, major bleeds in 3.09%, all-cause death in 3.94%, and hemorrhagic stroke in 0.47%. All of the differences between the two treatment groups were statistically significant. Over the median 1.8-year follow-up of the study, treatment of 1,000 patients with apixaban prevented on average six strokes (four hemorrhagic and two ischemic or unknown type), 15 major bleeds, and eight deaths compared with patients treated with warfarin.

Dr. Granger said that he has received grants and consultant fees from numerous pharmaceutical companies, including Boehringer Ingelheim. Dr. Brindis said that he had no disclosures. Dr. Wallentin has received research grants from Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, Roche, and Merck-Schering Plough, and has been an advisor or consultant to Portola, CSL Behring, Evola, Athera, and Regado. Dr. Ezekowitz said that he has been a consultant to and has received grants from numerous companies including Boehringer Ingelheim. He was also a co–principal investigator for the RE-LY study, on the executive committee of Engage AF, and lead investigator for betrixaban.

PARIS – The growing list of oral anticoagulant drugs jockeying to replace warfarin as the go-to agent for stroke prevention in patients with atrial fibrillation added a new candidate, apixaban, that appeared to immediately take the lead on the strength of strikingly impressive results in an 18,000-patient trial.

When matched against warfarin, atrial fibrillation (AF) patients treated with apixaban (Bristol-Myers Squibb, Pfizer) had significantly lower rates of stroke and systemic embolism, major bleeding complication, and overall mortality, compared with patients randomized to warfarin during a median follow-up of 1.8 years, Dr. Christopher B. Granger reported Aug. 28 at the annual congress of the European Society of Cardiology, and in a published article that concurrently appeared online (N. Engl. J. Med. 2011 Aug. 28 [10.1056/NEJMoa1107039]).

Heidi Splete/Elsevier Global Medical News

"Treatment with apixaban as compared with warfarin in patients with AF and at least one additional risk factor for stroke reduces stroke and systemic embolism by [a relative] 21%, reduces major bleeding by [a relative] 31%, and reduces mortality by [a relative] 11%," all statistically significant differences, reported Dr. Granger, director of the cardiac care unit at Duke University in Durham, N.C.

"I view the study as a home run. It is incredibly important, and it put another stake in the heart of warfarin in the management of atrial fibrillation to prevent stroke," commented Dr. Ralph Brindis, senior adviser for cardiovascular diseases at Northern California Kaiser.

Apixaban’s accomplishment in significantly surpassing warfarin’s performance for the trio of stroke prevention, bleeding safety, and overall mortality in its pivotal trial, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study, appeared to vault it ahead of dabigatran (Pradaxa, Boehringer Ingelheim), which received Food and Drug Administration approval for stroke prevention in AF patients last October, and the still-investigational agent rivaroxaban (Xarelto, Janssen), which the FDA is currently reviewing for a similar AF indication.

Neither dabigatran nor rivaroxaban could match apixaban’s performance in their respective pivotal AF trials: the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) study that matched dabigatran against warfarin in 18,113 randomized patients (N. Engl. J. Med. 2009;361:1139-51), and the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study that pitted rivaroxaban against warfarin in 14,264 randomized patients (N. Engl. J. Med. 2011 Aug. 10 [10.1056/NEJMoa1009638]).

In RE-LY, which tested two different dabigatran dosages, the 110-mg/b.i.d. dosage produced stroke and systemic embolism prevention that was noninferior to warfarin while leading to a statistically significant reduction in major bleeds, and the 150-mg/b.i.d. dosage (the primary dosage approved by the FDA) produced a statically significant reduction in strokes and systemic embolisms compared with warfarin while being noninferior to the comparator for major bleeds. In ROCKET-AF, once-daily treatment with rivaroxaban proved noninferior to warfarin for both the primary efficacy end point of fewer strokes and systemic embolisms and the safety end point of major bleeds.

"We think we hit the sweet spot in terms of the [apixaban] dose" in ARISTOTLE, said Dr. Granger, and although he and other experts warned against the pitfalls of cross-trial comparisons, many also acknowledged that mental calculations comparing the demonstrated pros and cons of each of these three new drugs are inevitable once all three drugs become routinely available.

Results from a study directly comparing two or all three of these drugs won’t be available soon, leaving it to clinicians to take into account not only the efficacy and safety performance of the three agents in these studies but other considerations as well, such as their prices, dosing convenience, adverse effects, and individual patient reactions.

"Apixaban has a certain edge because of its safety; [it] reduced all types of bleeding and had impressive tolerability," said Dr. Lars Wallentin, professor and head of cardiology research at Uppsala University in Sweden, and a coinvestigator in both the ARISTOTLE and RE-LY trials. Apixaban also has the attraction of having another major stroke-prevention in AF under its belt, the Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) study, which randomized 5,599 patients (N. Engl. J. Med. 2011;364:806-17).

"We have two [apixaban] trials [in] a large program, showing this safety. In AVERROES the bleeding risk with apixaban was the same as with low-dose aspirin," Dr. Wallentin said in an interview.

"I think it will be very competitive" among the three new drugs, said Dr. Michael D. Ezekowitz, professor of medicine at Thomas Jefferson University in Philadelphia and a lead investigator of the RE-LY trial. "That’s what we want; multiple agents competing, each one finding their niche in the huge field of atrial fibrillation treatment. The companies [that make these new drugs] will compete at multiple levels."

ARISTOTLE’s results showed that among patients randomized to apixaban, the rate of the primary stroke and systemic end point during follow-up was 1.27%, major bleeds occurred in 2.13%, the rate of death from any cause was 3.52%, and 0.24% of patients developed a hemorrhagic stroke. In patients randomized to warfarin, strokes or embolisms occurred in 1.60%, major bleeds in 3.09%, all-cause death in 3.94%, and hemorrhagic stroke in 0.47%. All of the differences between the two treatment groups were statistically significant. Over the median 1.8-year follow-up of the study, treatment of 1,000 patients with apixaban prevented on average six strokes (four hemorrhagic and two ischemic or unknown type), 15 major bleeds, and eight deaths compared with patients treated with warfarin.

Dr. Granger said that he has received grants and consultant fees from numerous pharmaceutical companies, including Boehringer Ingelheim. Dr. Brindis said that he had no disclosures. Dr. Wallentin has received research grants from Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, Roche, and Merck-Schering Plough, and has been an advisor or consultant to Portola, CSL Behring, Evola, Athera, and Regado. Dr. Ezekowitz said that he has been a consultant to and has received grants from numerous companies including Boehringer Ingelheim. He was also a co–principal investigator for the RE-LY study, on the executive committee of Engage AF, and lead investigator for betrixaban.

PARIS – The growing list of oral anticoagulant drugs jockeying to replace warfarin as the go-to agent for stroke prevention in patients with atrial fibrillation added a new candidate, apixaban, that appeared to immediately take the lead on the strength of strikingly impressive results in an 18,000-patient trial.

When matched against warfarin, atrial fibrillation (AF) patients treated with apixaban (Bristol-Myers Squibb, Pfizer) had significantly lower rates of stroke and systemic embolism, major bleeding complication, and overall mortality, compared with patients randomized to warfarin during a median follow-up of 1.8 years, Dr. Christopher B. Granger reported Aug. 28 at the annual congress of the European Society of Cardiology, and in a published article that concurrently appeared online (N. Engl. J. Med. 2011 Aug. 28 [10.1056/NEJMoa1107039]).

Heidi Splete/Elsevier Global Medical News

"Treatment with apixaban as compared with warfarin in patients with AF and at least one additional risk factor for stroke reduces stroke and systemic embolism by [a relative] 21%, reduces major bleeding by [a relative] 31%, and reduces mortality by [a relative] 11%," all statistically significant differences, reported Dr. Granger, director of the cardiac care unit at Duke University in Durham, N.C.

"I view the study as a home run. It is incredibly important, and it put another stake in the heart of warfarin in the management of atrial fibrillation to prevent stroke," commented Dr. Ralph Brindis, senior adviser for cardiovascular diseases at Northern California Kaiser.

Apixaban’s accomplishment in significantly surpassing warfarin’s performance for the trio of stroke prevention, bleeding safety, and overall mortality in its pivotal trial, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study, appeared to vault it ahead of dabigatran (Pradaxa, Boehringer Ingelheim), which received Food and Drug Administration approval for stroke prevention in AF patients last October, and the still-investigational agent rivaroxaban (Xarelto, Janssen), which the FDA is currently reviewing for a similar AF indication.

Neither dabigatran nor rivaroxaban could match apixaban’s performance in their respective pivotal AF trials: the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) study that matched dabigatran against warfarin in 18,113 randomized patients (N. Engl. J. Med. 2009;361:1139-51), and the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study that pitted rivaroxaban against warfarin in 14,264 randomized patients (N. Engl. J. Med. 2011 Aug. 10 [10.1056/NEJMoa1009638]).

In RE-LY, which tested two different dabigatran dosages, the 110-mg/b.i.d. dosage produced stroke and systemic embolism prevention that was noninferior to warfarin while leading to a statistically significant reduction in major bleeds, and the 150-mg/b.i.d. dosage (the primary dosage approved by the FDA) produced a statically significant reduction in strokes and systemic embolisms compared with warfarin while being noninferior to the comparator for major bleeds. In ROCKET-AF, once-daily treatment with rivaroxaban proved noninferior to warfarin for both the primary efficacy end point of fewer strokes and systemic embolisms and the safety end point of major bleeds.

"We think we hit the sweet spot in terms of the [apixaban] dose" in ARISTOTLE, said Dr. Granger, and although he and other experts warned against the pitfalls of cross-trial comparisons, many also acknowledged that mental calculations comparing the demonstrated pros and cons of each of these three new drugs are inevitable once all three drugs become routinely available.

Results from a study directly comparing two or all three of these drugs won’t be available soon, leaving it to clinicians to take into account not only the efficacy and safety performance of the three agents in these studies but other considerations as well, such as their prices, dosing convenience, adverse effects, and individual patient reactions.

"Apixaban has a certain edge because of its safety; [it] reduced all types of bleeding and had impressive tolerability," said Dr. Lars Wallentin, professor and head of cardiology research at Uppsala University in Sweden, and a coinvestigator in both the ARISTOTLE and RE-LY trials. Apixaban also has the attraction of having another major stroke-prevention in AF under its belt, the Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) study, which randomized 5,599 patients (N. Engl. J. Med. 2011;364:806-17).

"We have two [apixaban] trials [in] a large program, showing this safety. In AVERROES the bleeding risk with apixaban was the same as with low-dose aspirin," Dr. Wallentin said in an interview.

"I think it will be very competitive" among the three new drugs, said Dr. Michael D. Ezekowitz, professor of medicine at Thomas Jefferson University in Philadelphia and a lead investigator of the RE-LY trial. "That’s what we want; multiple agents competing, each one finding their niche in the huge field of atrial fibrillation treatment. The companies [that make these new drugs] will compete at multiple levels."

ARISTOTLE’s results showed that among patients randomized to apixaban, the rate of the primary stroke and systemic end point during follow-up was 1.27%, major bleeds occurred in 2.13%, the rate of death from any cause was 3.52%, and 0.24% of patients developed a hemorrhagic stroke. In patients randomized to warfarin, strokes or embolisms occurred in 1.60%, major bleeds in 3.09%, all-cause death in 3.94%, and hemorrhagic stroke in 0.47%. All of the differences between the two treatment groups were statistically significant. Over the median 1.8-year follow-up of the study, treatment of 1,000 patients with apixaban prevented on average six strokes (four hemorrhagic and two ischemic or unknown type), 15 major bleeds, and eight deaths compared with patients treated with warfarin.

Dr. Granger said that he has received grants and consultant fees from numerous pharmaceutical companies, including Boehringer Ingelheim. Dr. Brindis said that he had no disclosures. Dr. Wallentin has received research grants from Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, Roche, and Merck-Schering Plough, and has been an advisor or consultant to Portola, CSL Behring, Evola, Athera, and Regado. Dr. Ezekowitz said that he has been a consultant to and has received grants from numerous companies including Boehringer Ingelheim. He was also a co–principal investigator for the RE-LY study, on the executive committee of Engage AF, and lead investigator for betrixaban.

PARIS – Apixaban treatment produced better outcomes in atrial fibrillation patients compared with warfarin in the ARISTOTLE trial, regardless of the quality of warfarin treatment the comparator patients received, raising the possibility that all atrial fibrillation patients might benefit by switching from warfarin to apixaban.

"The benefits of apixaban over warfarin in preventing stroke, reducing bleeding, and improving survival appear consistent regardless of a center’s quality of INR [international normalized ratio] control. Therefore, in patients with atrial fibrillation, apixaban is a safer and more effective treatment than warfarin across a wide range of warfarin management," Dr. Lars Wallentin said at the annual congress of the European Society of Cardiology. Assessment of apixaban’s efficacy and safety relative to warfarin across the range of warfarin care that was delivered was one of the trial’s prespecified analyses.

"It’s a very important question, [whether] a patient with very good INR control [could] benefit from switching to apixaban," commented Dr. Jean-Philippe Collet, a cardiologist at the Institute of Cardiology at Pitié Salpêtrière Hospital, Paris. "The local standards of care do not affect the benefits of apixaban over warfarin."

The time that patients spend in the INR therapeutic range of 2-3 is a marker of a patient’s risk, the quality of care that patients with atrial fibrillation (AF) receive, and patient outcomes, and probably can be used to compare different AF treatment studies, but "it is not a marker of the superiority of apixaban over warfarin," Dr. Collet said.

To assess the impact that the average quality of warfarin treatment had in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) study, Dr. Wallentin and his associates calculated a median time in therapeutic range (TTR) for the more than 9,000 patients treated with warfarin in ARISTOTLE.

The researchers then calculated a median TTR for each of the 1,034 sites that participated in the trial. The median levels showed marked variability. When the medians were averaged for all sites in each of the 39 countries where they were located, the countrywide median TTRs ranged from a high of about 80% in Sweden to a low of about 45% in India.

The researchers then divided the centers into quartiles based on their median TTRs. The lowest quartile included centers with median TTRs of 58% or less, whereas the highest quartile had centers with median TTRs of 72% or greater, reported Dr. Wallentin, professor and head of cardiology research at Uppsala (Sweden) University. The analysis then examined the relative outcomes of the patients treated with apixaban and those treated with warfarin within each of the quartiles.

The hazard ratio between apixaban and warfarin treatment for the study’s primary outcome of the rate of strokes and systemic embolism showed consistency across all four quartiles. At the centers in the quartile with the best warfarin TTRs, apixaban treatment reduced the outcome by a relative 19% compared with patients treated with warfarin. At the centers with the poorest performance of keeping patients in their therapeutic range, apixaban improved the primary outcome by a relative 23%. The hazard ratio in the other two quartiles fell between these two, with relative risk reductions of 19% and 20%. The other study outcomes, such as the relative rates of major bleeds, and mortality showed a similarly consistent pattern across the four quartiles of median TTRs.

Dr. Wallentin said has received research grants from Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, Roche, and Merck-Schering Plough, and has been an advisor or consultant to Portola, CSL Behring, Evola, Athera, and Regado. Dr. Collet has received research grants, and lecture and consulting fees from Bristol-Myers Squibb, Sanofi-Aventis, and Eli Lilly. He has also reported receiving research grants from Guerbet Medical, Medtronic, Boston Scientific, Cordis, Stago, and Centocor.

PARIS – Apixaban treatment produced better outcomes in atrial fibrillation patients compared with warfarin in the ARISTOTLE trial, regardless of the quality of warfarin treatment the comparator patients received, raising the possibility that all atrial fibrillation patients might benefit by switching from warfarin to apixaban.

"The benefits of apixaban over warfarin in preventing stroke, reducing bleeding, and improving survival appear consistent regardless of a center’s quality of INR [international normalized ratio] control. Therefore, in patients with atrial fibrillation, apixaban is a safer and more effective treatment than warfarin across a wide range of warfarin management," Dr. Lars Wallentin said at the annual congress of the European Society of Cardiology. Assessment of apixaban’s efficacy and safety relative to warfarin across the range of warfarin care that was delivered was one of the trial’s prespecified analyses.

"It’s a very important question, [whether] a patient with very good INR control [could] benefit from switching to apixaban," commented Dr. Jean-Philippe Collet, a cardiologist at the Institute of Cardiology at Pitié Salpêtrière Hospital, Paris. "The local standards of care do not affect the benefits of apixaban over warfarin."

The time that patients spend in the INR therapeutic range of 2-3 is a marker of a patient’s risk, the quality of care that patients with atrial fibrillation (AF) receive, and patient outcomes, and probably can be used to compare different AF treatment studies, but "it is not a marker of the superiority of apixaban over warfarin," Dr. Collet said.

To assess the impact that the average quality of warfarin treatment had in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) study, Dr. Wallentin and his associates calculated a median time in therapeutic range (TTR) for the more than 9,000 patients treated with warfarin in ARISTOTLE.

The researchers then calculated a median TTR for each of the 1,034 sites that participated in the trial. The median levels showed marked variability. When the medians were averaged for all sites in each of the 39 countries where they were located, the countrywide median TTRs ranged from a high of about 80% in Sweden to a low of about 45% in India.

The researchers then divided the centers into quartiles based on their median TTRs. The lowest quartile included centers with median TTRs of 58% or less, whereas the highest quartile had centers with median TTRs of 72% or greater, reported Dr. Wallentin, professor and head of cardiology research at Uppsala (Sweden) University. The analysis then examined the relative outcomes of the patients treated with apixaban and those treated with warfarin within each of the quartiles.

The hazard ratio between apixaban and warfarin treatment for the study’s primary outcome of the rate of strokes and systemic embolism showed consistency across all four quartiles. At the centers in the quartile with the best warfarin TTRs, apixaban treatment reduced the outcome by a relative 19% compared with patients treated with warfarin. At the centers with the poorest performance of keeping patients in their therapeutic range, apixaban improved the primary outcome by a relative 23%. The hazard ratio in the other two quartiles fell between these two, with relative risk reductions of 19% and 20%. The other study outcomes, such as the relative rates of major bleeds, and mortality showed a similarly consistent pattern across the four quartiles of median TTRs.

Dr. Wallentin said has received research grants from Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, Roche, and Merck-Schering Plough, and has been an advisor or consultant to Portola, CSL Behring, Evola, Athera, and Regado. Dr. Collet has received research grants, and lecture and consulting fees from Bristol-Myers Squibb, Sanofi-Aventis, and Eli Lilly. He has also reported receiving research grants from Guerbet Medical, Medtronic, Boston Scientific, Cordis, Stago, and Centocor.

PARIS – Apixaban treatment produced better outcomes in atrial fibrillation patients compared with warfarin in the ARISTOTLE trial, regardless of the quality of warfarin treatment the comparator patients received, raising the possibility that all atrial fibrillation patients might benefit by switching from warfarin to apixaban.

"The benefits of apixaban over warfarin in preventing stroke, reducing bleeding, and improving survival appear consistent regardless of a center’s quality of INR [international normalized ratio] control. Therefore, in patients with atrial fibrillation, apixaban is a safer and more effective treatment than warfarin across a wide range of warfarin management," Dr. Lars Wallentin said at the annual congress of the European Society of Cardiology. Assessment of apixaban’s efficacy and safety relative to warfarin across the range of warfarin care that was delivered was one of the trial’s prespecified analyses.

"It’s a very important question, [whether] a patient with very good INR control [could] benefit from switching to apixaban," commented Dr. Jean-Philippe Collet, a cardiologist at the Institute of Cardiology at Pitié Salpêtrière Hospital, Paris. "The local standards of care do not affect the benefits of apixaban over warfarin."

The time that patients spend in the INR therapeutic range of 2-3 is a marker of a patient’s risk, the quality of care that patients with atrial fibrillation (AF) receive, and patient outcomes, and probably can be used to compare different AF treatment studies, but "it is not a marker of the superiority of apixaban over warfarin," Dr. Collet said.

To assess the impact that the average quality of warfarin treatment had in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) study, Dr. Wallentin and his associates calculated a median time in therapeutic range (TTR) for the more than 9,000 patients treated with warfarin in ARISTOTLE.

The researchers then calculated a median TTR for each of the 1,034 sites that participated in the trial. The median levels showed marked variability. When the medians were averaged for all sites in each of the 39 countries where they were located, the countrywide median TTRs ranged from a high of about 80% in Sweden to a low of about 45% in India.

The researchers then divided the centers into quartiles based on their median TTRs. The lowest quartile included centers with median TTRs of 58% or less, whereas the highest quartile had centers with median TTRs of 72% or greater, reported Dr. Wallentin, professor and head of cardiology research at Uppsala (Sweden) University. The analysis then examined the relative outcomes of the patients treated with apixaban and those treated with warfarin within each of the quartiles.

The hazard ratio between apixaban and warfarin treatment for the study’s primary outcome of the rate of strokes and systemic embolism showed consistency across all four quartiles. At the centers in the quartile with the best warfarin TTRs, apixaban treatment reduced the outcome by a relative 19% compared with patients treated with warfarin. At the centers with the poorest performance of keeping patients in their therapeutic range, apixaban improved the primary outcome by a relative 23%. The hazard ratio in the other two quartiles fell between these two, with relative risk reductions of 19% and 20%. The other study outcomes, such as the relative rates of major bleeds, and mortality showed a similarly consistent pattern across the four quartiles of median TTRs.

Dr. Wallentin said has received research grants from Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, Roche, and Merck-Schering Plough, and has been an advisor or consultant to Portola, CSL Behring, Evola, Athera, and Regado. Dr. Collet has received research grants, and lecture and consulting fees from Bristol-Myers Squibb, Sanofi-Aventis, and Eli Lilly. He has also reported receiving research grants from Guerbet Medical, Medtronic, Boston Scientific, Cordis, Stago, and Centocor.