AHA 2012: Prevention a key focus of meeting

Abstract

The American Heart Association (AHA) Scientific Sessions 2012 brought together leading experts from around the world to discuss successes and new initiatives aimed at reducing the burden of cardiovascular disease (CVD). A key focus of the meeting was on treatments aimed at preventing cardiovascular events. In addition, the meeting discussed the efficacy of novel therapies and safety of marketed treatments. A review of select late-breaking trials and other presentations will be covered in this article. The American Heart Association (AHA) Scientific Sessions 2012 brought together leading experts from around the world to discuss successes and new initiatives aimed at reducing the burden of cardiovascular disease (CVD). A key focus of the meeting was on treatments aimed at preventing cardiovascular events. In addition, the meeting discussed the efficacy of novel therapies and safety of marketed treatments. A review of select late-breaking trials and other presentations will be covered in this article. Fish oils for atrial fibrillationAccording to two studies presented at one of AHA's sessions on late-breaking clinical trials, use of omega-3 fatty acids (i.e., fish oil) is not effective in preventing atrial fibrillation in either the chronic or acute setting.■Results of FORWARD and OPERA make it clear that there is no current role for the use of omega-3 fatty acids for the prevention of atrial fibrillation.■New data support the longterm safety profile and efficacy of dabigatran for stroke prevention in atrial fibrillation.The FORWARD (Fish Oil Research With Omega-3 for Atrial Fibrillation Recurrence Delay) trial, presented by Alejandro Macchia, MD, assessed the chronic use of omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation. A total of 586 patients with confirmed symptomatic paroxysmal atrial fibrillation that required cardioversion and/or at least two episodes of atrial fibrillation in the previous 6 months were included in the trial. Patients were randomized to receive 1 g/d of omega-3 fatty acids or placebo for 12 months.At the end of the treatment period, no difference was observed between groups for the primary endpoint of first symptomatic recurrence of atrial fibrillation (18.9% placebo vs. 24.0% omega-3 fatty acids, P = 0.17). In addition, no differences were observed for other secondary endpoints such as the composite endpoint of all-cause mortality, nonfatal stroke, nonfatal acute myocardial infarction, systemic embolism, heart failure development, or severe bleeding (6.7% placebo vs. 5.5% omega-3 fatty acids, P = 0.65).The OPERA (Omega-3 Fatty Acids for Prevention of Postoperative Atrial Fibrillation) trial, presented by Roberto Marchioli, MD, and simultaneously published online in JAMA, assessed the short-term use of omega-3 fatty acids to prevent postoperative atrial fibrillation. A total of 1,516 patients scheduled to undergo cardiac surgery were randomized to receive placebo or a preoperative loading dose of 10 g omega-3 fatty acids over 3 days to 5 days or 8 g over 2 days, followed by a postoperative dose of 2 g/d until discharge or day 10, whichever occurred first.Results from OPERA showed that the occurrence of the primary endpoint, which was postoperative atrial fibrillation lasting longer than 30 seconds, was similar in both groups at approximately 30% (P = 0.74). In addition, no significant differences were observed for any of the secondary endpoints, such as postoperative atrial fibrillation that was sustained, symptomatic, or treated, or number of postoperative atrial fibrillation episodes per patient."In this setting—patients undergoing cardiac surgery—omega-3 polyunsaturated fatty acids may simply not be powerful enough to be effective in preventing arrhythmias," Marcholi commented in a media briefing, adding that "the same could be true in other settings where arrhythmias are already established." In fact, this was case in FORWARD, where omega-3 fatty acids had no benefit in those with established arrhythmias. The results of FORWARD and OPERA make it clear that there is no current role for the use of omega-3 fatty acids for the prevention of atrial fibrillation.Polypill enhances adherenceLong-term adherence to multiple medications after an acute coronary event is generally poor, with an estimated one-third to one-half of patients failing to take all recommended treatments a year or more after an event. In an effort to enhance adherence in those with or at high risk of CVD, the UMPIRE (Use of a Multidrug Pill in Reducing Cardiovascular Events) trial was conducted to assess the use of a fixed-dose combination tablet containing four medications compared with the standard of care. A total of 2,004 patients with established CVD or an estimated 5-year CVD risk of 15% or more were randomized to standard of care or one of the following fixed-dose combinations: aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg, and atenolol 50 mg or aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg, and hydrochlorothiazide 12.5 mg.Results from UMPIRE presented by Simon Thom showed that use of the fixed-dose combination tablets significantly improved adherence rates and led to significant reductions in both LDL cholesterol and blood pressure levels. Self-reported adherence rates were improved by 33% with the combination tablet, and this positive adherence effect was associated with a 2.6 mm Hg reduction in systolic blood pressure and a 0.11 mmol/L reduction in LDL cholesterol. The effects were sustained over the 15-month follow-up period.Experts discussing these results at the AHA Scientific Sessions opined that the approach of giving high-risk patients a single tablet to enhance adherence was a good idea. In fact, Andrew Tonkin noted that the UMPIRE results likely underestimated the true benefit of the "polypill" approach since the standard of care group had a high level of adherence to prescribed treatments. Additional long-term studies are needed to determine the effects of these types of combination tablets on long-term cardiovascular morbidity and mortality. Until that time, Tonkin said, "both physicians and government should pay attention to these results."Flaxseed's effects on BPFlaxseed has been shown to have cardioprotective effects in animal models. Based on this fact, Delfin Rodriguez and colleagues assessed the antihypertensive effects of flaxseed in 110 patients with peripheral artery disease in the FLAX-PAD trial. The majority of patients (80%) were already receiving antihypertensive medications at baseline. Patients were randomized to placebo or milled flaxseed 30 g in the form of bagels, muffins, and buns daily for 6 months.The investigators reported that systolic blood pressure increased by 3 mm Hg and diastolic blood pressure remained unchanged in the placebo group, while systolic blood pressure was approximately 10 mm Hg lower and diastolic blood pressure was approximately 8 mm Hg lower in the flaxseed group (P < 0.04 and P < 0.004, respectively). In addition, in patients with a systolic blood pressure of 140 mm Hg or greater at baseline, use of flaxseed resulted in sustained and significant 15 mm Hg and 7 mm Hg reductions in systolic and diastolic blood pressure, respectively, over the 6-month treatment period."This trial identified one of the most potent antihypertensive effects ever observed by a dietary intervention," the investigators wrote. "This change in blood pressure would be predicted to result in an approximately 50% and 30% decrease in the incidence of strokes and myocardial infarction, respectively." The researchers concluded that "dietary flaxseed represents an appealing strategy for treating hypertension in economically disadvantaged populations."Long-term dabigatran data supports safety, efficacyAn extension study to RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy), which evaluated more than 2 additional years of data for dabigatran (Pradaxa—Boehringer-Ingelheim), found no new safety signals and sustained efficacy for stroke prevention in patients with atrial fibrillation.The RELY-ABLE (Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation) trial was designed to provide additional long-term data on the use of dabigatran in patients who completed RE-LY. Patients enrolled in RELY-ABLE continued to receive the same dose of dabigatran as the original trial, with 2,937 patients using dabigatran 150 mg twice daily and 2,914 receiving 110 mg twice daily. There was no warfarin comparator group in the extension study. The median duration of followup was 4.3 years from the beginning of RE-LY to the end of RELY-ABLE, with the extension trial providing an additional 2.3 years of follow-up.The results from RELY-ABLE showed that the rates of ischemic stroke were 1.15% per year for the 150-mg dose and 1.24% per year for the 110-mg dose, while incidence of hemorrhagic stroke was 0.13% per year and 0.14% per year, respectively, for those doses. In addition, rates of major bleeding were 3.74% per year for the 150-mg dose and 2.99% per year for the 110-mg dose, while rates of intracranial bleeding were 0.33% per year and 0.25% per year, respectively, for the two doses. These results were consistent with those observed in RELY. Patients in RELY-ABLE differed in several respects from those in the original trial, however, with continuing patients less likely to have permanent atrial fibrillation, heart failure, or a major clinical event during the RE-LY trial."The results from the RELY-ABLE study are consistent with the excellent results we have seen in the RE-LY trial and strongly support the long-term safety profile and efficacy of Pradaxa for stroke prevention in atrial fibrillation," said Klaus Dugi, Boehringer-Ingelheim Senior Vice President of Medicine, in a news release. "Physicians can be confident in the sustained brain protection and treatment advantages offered by both doses of Pradaxa and can tailor their treatment according to patient needs, as these first long-term clinical data for a novel oral anticoagulant show."The safety associated with using dabigatran was further supported by an FDA safety communication released in early November, in which the agency concluded that bleeding rates associated with new use of dabigatran do not appear to be higher than bleeding rates associated with new use of warfarin. The agency assessed actual rates of gastrointestinal bleeding and intracranial hemorrhage for new users of dabigatran compared with new users of warfarin using insurance claims and administrative data from FDA's MiniSentinel pilot of the Sentinel Initiative.An assessment of these data showed that the combined incidence rate of gastrointestinal hemorrhage and intracranial hemorrhage events per 100,000 days at risk was 1.8 to 2.6 times higher for new users of warfarin than for new users of dabigatran. In addition, the incidence rate of gastrointestinal hemorrhage events only per 100,000 days at risk was 1.6 to 2.2 times higher for new users of warfarin than for new users of dabigatran, and the incidence rate of intracranial hemorrhage events only per 100,000 days at risk was 2.1 to 3.0 times higher with warfarin than with dabigatran. Based on these results, FDA concluded that the observed bleeding rates associated with new use of dabigatran do not appear to be higher than the bleeding rates associated with new use of warfarin.Impact on current practiceThis article provides only a snapshot of key trials presented at AHA. Based on the results of OPERA, FORWARD, UMPIRE, FLAX-PAD, and RELY-ABLE, there is no role for the use of omega-3 fatty acids to prevent atrial fibrillation, a fixed-dose combination tablet may enhance adherence, increased dietary intake of flaxseed may be a good option to reduce blood pressure, and dabigatran appears to be safe and efficacious when used long-term. Fish oils for atrial fibrillationAccording to two studies presented at one of AHA's sessions on late-breaking clinical trials, use of omega-3 fatty acids (i.e., fish oil) is not effective in preventing atrial fibrillation in either the chronic or acute setting.■Results of FORWARD and OPERA make it clear that there is no current role for the use of omega-3 fatty acids for the prevention of atrial fibrillation.■New data support the longterm safety profile and efficacy of dabigatran for stroke prevention in atrial fibrillation.The FORWARD (Fish Oil Research With Omega-3 for Atrial Fibrillation Recurrence Delay) trial, presented by Alejandro Macchia, MD, assessed the chronic use of omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation. A total of 586 patients with confirmed symptomatic paroxysmal atrial fibrillation that required cardioversion and/or at least two episodes of atrial fibrillation in the previous 6 months were included in the trial. Patients were randomized to receive 1 g/d of omega-3 fatty acids or placebo for 12 months.At the end of the treatment period, no difference was observed between groups for the primary endpoint of first symptomatic recurrence of atrial fibrillation (18.9% placebo vs. 24.0% omega-3 fatty acids, P = 0.17). In addition, no differences were observed for other secondary endpoints such as the composite endpoint of all-cause mortality, nonfatal stroke, nonfatal acute myocardial infarction, systemic embolism, heart failure development, or severe bleeding (6.7% placebo vs. 5.5% omega-3 fatty acids, P = 0.65).The OPERA (Omega-3 Fatty Acids for Prevention of Postoperative Atrial Fibrillation) trial, presented by Roberto Marchioli, MD, and simultaneously published online in JAMA, assessed the short-term use of omega-3 fatty acids to prevent postoperative atrial fibrillation. A total of 1,516 patients scheduled to undergo cardiac surgery were randomized to receive placebo or a preoperative loading dose of 10 g omega-3 fatty acids over 3 days to 5 days or 8 g over 2 days, followed by a postoperative dose of 2 g/d until discharge or day 10, whichever occurred first.Results from OPERA showed that the occurrence of the primary endpoint, which was postoperative atrial fibrillation lasting longer than 30 seconds, was similar in both groups at approximately 30% (P = 0.74). In addition, no significant differences were observed for any of the secondary endpoints, such as postoperative atrial fibrillation that was sustained, symptomatic, or treated, or number of postoperative atrial fibrillation episodes per patient."In this setting—patients undergoing cardiac surgery—omega-3 polyunsaturated fatty acids may simply not be powerful enough to be effective in preventing arrhythmias," Marcholi commented in a media briefing, adding that "the same could be true in other settings where arrhythmias are already established." In fact, this was case in FORWARD, where omega-3 fatty acids had no benefit in those with established arrhythmias. The results of FORWARD and OPERA make it clear that there is no current role for the use of omega-3 fatty acids for the prevention of atrial fibrillation. According to two studies presented at one of AHA's sessions on late-breaking clinical trials, use of omega-3 fatty acids (i.e., fish oil) is not effective in preventing atrial fibrillation in either the chronic or acute setting. ■Results of FORWARD and OPERA make it clear that there is no current role for the use of omega-3 fatty acids for the prevention of atrial fibrillation.■New data support the longterm safety profile and efficacy of dabigatran for stroke prevention in atrial fibrillation. ■Results of FORWARD and OPERA make it clear that there is no current role for the use of omega-3 fatty acids for the prevention of atrial fibrillation.■New data support the longterm safety profile and efficacy of dabigatran for stroke prevention in atrial fibrillation. ■Results of FORWARD and OPERA make it clear that there is no current role for the use of omega-3 fatty acids for the prevention of atrial fibrillation.■New data support the longterm safety profile and efficacy of dabigatran for stroke prevention in atrial fibrillation. The FORWARD (Fish Oil Research With Omega-3 for Atrial Fibrillation Recurrence Delay) trial, presented by Alejandro Macchia, MD, assessed the chronic use of omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation. A total of 586 patients with confirmed symptomatic paroxysmal atrial fibrillation that required cardioversion and/or at least two episodes of atrial fibrillation in the previous 6 months were included in the trial. Patients were randomized to receive 1 g/d of omega-3 fatty acids or placebo for 12 months. At the end of the treatment period, no difference was observed between groups for the primary endpoint of first symptomatic recurrence of atrial fibrillation (18.9% placebo vs. 24.0% omega-3 fatty acids, P = 0.17). In addition, no differences were observed for other secondary endpoints such as the composite endpoint of all-cause mortality, nonfatal stroke, nonfatal acute myocardial infarction, systemic embolism, heart failure development, or severe bleeding (6.7% placebo vs. 5.5% omega-3 fatty acids, P = 0.65). The OPERA (Omega-3 Fatty Acids for Prevention of Postoperative Atrial Fibrillation) trial, presented by Roberto Marchioli, MD, and simultaneously published online in JAMA, assessed the short-term use of omega-3 fatty acids to prevent postoperative atrial fibrillation. A total of 1,516 patients scheduled to undergo cardiac surgery were randomized to receive placebo or a preoperative loading dose of 10 g omega-3 fatty acids over 3 days to 5 days or 8 g over 2 days, followed by a postoperative dose of 2 g/d until discharge or day 10, whichever occurred first. Results from OPERA showed that the occurrence of the primary endpoint, which was postoperative atrial fibrillation lasting longer than 30 seconds, was similar in both groups at approximately 30% (P = 0.74). In addition, no significant differences were observed for any of the secondary endpoints, such as postoperative atrial fibrillation that was sustained, symptomatic, or treated, or number of postoperative atrial fibrillation episodes per patient. "In this setting—patients undergoing cardiac surgery—omega-3 polyunsaturated fatty acids may simply not be powerful enough to be effective in preventing arrhythmias," Marcholi commented in a media briefing, adding that "the same could be true in other settings where arrhythmias are already established." In fact, this was case in FORWARD, where omega-3 fatty acids had no benefit in those with established arrhythmias. The results of FORWARD and OPERA make it clear that there is no current role for the use of omega-3 fatty acids for the prevention of atrial fibrillation. Polypill enhances adherenceLong-term adherence to multiple medications after an acute coronary event is generally poor, with an estimated one-third to one-half of patients failing to take all recommended treatments a year or more after an event. In an effort to enhance adherence in those with or at high risk of CVD, the UMPIRE (Use of a Multidrug Pill in Reducing Cardiovascular Events) trial was conducted to assess the use of a fixed-dose combination tablet containing four medications compared with the standard of care. A total of 2,004 patients with established CVD or an estimated 5-year CVD risk of 15% or more were randomized to standard of care or one of the following fixed-dose combinations: aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg, and atenolol 50 mg or aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg, and hydrochlorothiazide 12.5 mg.Results from UMPIRE presented by Simon Thom showed that use of the fixed-dose combination tablets significantly improved adherence rates and led to significant reductions in both LDL cholesterol and blood pressure levels. Self-reported adherence rates were improved by 33% with the combination tablet, and this positive adherence effect was associated with a 2.6 mm Hg reduction in systolic blood pressure and a 0.11 mmol/L reduction in LDL cholesterol. The effects were sustained over the 15-month follow-up period.Experts discussing these results at the AHA Scientific Sessions opined that the approach of giving high-risk patients a single tablet to enhance adherence was a good idea. In fact, Andrew Tonkin noted that the UMPIRE results likely underestimated the true benefit of the "polypill" approach since the standard of care group had a high level of adherence to prescribed treatments. Additional long-term studies are needed to determine the effects of these types of combination tablets on long-term cardiovascular morbidity and mortality. Until that time, Tonkin said, "both physicians and government should pay attention to these results." Long-term adherence to multiple medications after an acute coronary event is generally poor, with an estimated one-third to one-half of patients failing to take all recommended treatments a year or more after an event. In an effort to enhance adherence in those with or at high risk of CVD, the UMPIRE (Use of a Multidrug Pill in Reducing Cardiovascular Events) trial was conducted to assess the use of a fixed-dose combination tablet containing four medications compared with the standard of care. A total of 2,004 patients with established CVD or an estimated 5-year CVD risk of 15% or more were randomized to standard of care or one of the following fixed-dose combinations: aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg, and atenolol 50 mg or aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg, and hydrochlorothiazide 12.5 mg. Results from UMPIRE presented by Simon Thom showed that use of the fixed-dose combination tablets significantly improved adherence rates and led to significant reductions in both LDL cholesterol and blood pressure levels. Self-reported adherence rates were improved by 33% with the combination tablet, and this positive adherence effect was associated with a 2.6 mm Hg reduction in systolic blood pressure and a 0.11 mmol/L reduction in LDL cholesterol. The effects were sustained over the 15-month follow-up period. Experts discussing these results at the AHA Scientific Sessions opined that the approach of giving high-risk patients a single tablet to enhance adherence was a good idea. In fact, Andrew Tonkin noted that the UMPIRE results likely underestimated the true benefit of the "polypill" approach since the standard of care group had a high level of adherence to prescribed treatments. Additional long-term studies are needed to determine the effects of these types of combination tablets on long-term cardiovascular morbidity and mortality. Until that time, Tonkin said, "both physicians and government should pay attention to these results." Flaxseed's effects on BPFlaxseed has been shown to have cardioprotective effects in animal models. Based on this fact, Delfin Rodriguez and colleagues assessed the antihypertensive effects of flaxseed in 110 patients with peripheral artery disease in the FLAX-PAD trial. The majority of patients (80%) were already receiving antihypertensive medications at baseline. Patients were randomized to placebo or milled flaxseed 30 g in the form of bagels, muffins, and buns daily for 6 months.The investigators reported that systolic blood pressure increased by 3 mm Hg and diastolic blood pressure remained unchanged in the placebo group, while systolic blood pressure was approximately 10 mm Hg lower and diastolic blood pressure was approximately 8 mm Hg lower in the flaxseed group (P < 0.04 and P < 0.004, respectively). In addition, in patients with a systolic blood pressure of 140 mm Hg or greater at baseline, use of flaxseed resulted in sustained and significant 15 mm Hg and 7 mm Hg reductions in systolic and diastolic blood pressure, respectively, over the 6-month treatment period."This trial identified one of the most potent antihypertensive effects ever observed by a dietary intervention," the investigators wrote. "This change in blood pressure would be predicted to result in an approximately 50% and 30% decrease in the incidence of strokes and myocardial infarction, respectively." The researchers concluded that "dietary flaxseed represents an appealing strategy for treating hypertension in economically disadvantaged populations." Flaxseed has been shown to have cardioprotective effects in animal models. Based on this fact, Delfin Rodriguez and colleagues assessed the antihypertensive effects of flaxseed in 110 patients with peripheral artery disease in the FLAX-PAD trial. The majority of patients (80%) were already receiving antihypertensive medications at baseline. Patients were randomized to placebo or milled flaxseed 30 g in the form of bagels, muffins, and buns daily for 6 months. The investigators reported that systolic blood pressure increased by 3 mm Hg and diastolic blood pressure remained unchanged in the placebo group, while systolic blood pressure was approximately 10 mm Hg lower and diastolic blood pressure was approximately 8 mm Hg lower in the flaxseed group (P < 0.04 and P < 0.004, respectively). In addition, in patients with a systolic blood pressure of 140 mm Hg or greater at baseline, use of flaxseed resulted in sustained and significant 15 mm Hg and 7 mm Hg reductions in systolic and diastolic blood pressure, respectively, over the 6-month treatment period. "This trial identified one of the most potent antihypertensive effects ever observed by a dietary intervention," the investigators wrote. "This change in blood pressure would be predicted to result in an approximately 50% and 30% decrease in the incidence of strokes and myocardial infarction, respectively." The researchers concluded that "dietary flaxseed represents an appealing strategy for treating hypertension in economically disadvantaged populations." Long-term dabigatran data supports safety, efficacyAn extension study to RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy), which evaluated more than 2 additional years of data for dabigatran (Pradaxa—Boehringer-Ingelheim), found no new safety signals and sustained efficacy for stroke prevention in patients with atrial fibrillation.The RELY-ABLE (Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation) trial was designed to provide additional long-term data on the use of dabigatran in patients who completed RE-LY. Patients enrolled in RELY-ABLE continued to receive the same dose of dabigatran as the original trial, with 2,937 patients using dabigatran 150 mg twice daily and 2,914 receiving 110 mg twice daily. There was no warfarin comparator group in the extension study. The median duration of followup was 4.3 years from the beginning of RE-LY to the end of RELY-ABLE, with the extension trial providing an additional 2.3 years of follow-up.The results from RELY-ABLE showed that the rates of ischemic stroke were 1.15% per year for the 150-mg dose and 1.24% per year for the 110-mg dose, while incidence of hemorrhagic stroke was 0.13% per year and 0.14% per year, respectively, for those doses. In addition, rates of major bleeding were 3.74% per year for the 150-mg dose and 2.99% per year for the 110-mg dose, while rates of intracranial bleeding were 0.33% per year and 0.25% per year, respectively, for the two doses. These results were consistent with those observed in RELY. Patients in RELY-ABLE differed in several respects from those in the original trial, however, with continuing patients less likely to have permanent atrial fibrillation, heart failure, or a major clinical event during the RE-LY trial."The results from the RELY-ABLE study are consistent with the excellent results we have seen in the RE-LY trial and strongly support the long-term safety profile and efficacy of Pradaxa for stroke prevention in atrial fibrillation," said Klaus Dugi, Boehringer-Ingelheim Senior Vice President of Medicine, in a news release. "Physicians can be confident in the sustained brain protection and treatment advantages offered by both doses of Pradaxa and can tailor their treatment according to patient needs, as these first long-term clinical data for a novel oral anticoagulant show."The safety associated with using dabigatran was further supported by an FDA safety communication released in early November, in which the agency concluded that bleeding rates associated with new use of dabigatran do not appear to be higher than bleeding rates associated with new use of warfarin. The agency assessed actual rates of gastrointestinal bleeding and intracranial hemorrhage for new users of dabigatran compared with new users of warfarin using insurance claims and administrative data from FDA's MiniSentinel pilot of the Sentinel Initiative.An assessment of these data showed that the combined incidence rate of gastrointestinal hemorrhage and intracranial hemorrhage events per 100,000 days at risk was 1.8 to 2.6 times higher for new users of warfarin than for new users of dabigatran. In addition, the incidence rate of gastrointestinal hemorrhage events only per 100,000 days at risk was 1.6 to 2.2 times higher for new users of warfarin than for new users of dabigatran, and the incidence rate of intracranial hemorrhage events only per 100,000 days at risk was 2.1 to 3.0 times higher with warfarin than with dabigatran. Based on these results, FDA concluded that the observed bleeding rates associated with new use of dabigatran do not appear to be higher than the bleeding rates associated with new use of warfarin. An extension study to RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy), which evaluated more than 2 additional years of data for dabigatran (Pradaxa—Boehringer-Ingelheim), found no new safety signals and sustained efficacy for stroke prevention in patients with atrial fibrillation. The RELY-ABLE (Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation) trial was designed to provide additional long-term data on the use of dabigatran in patients who completed RE-LY. Patients enrolled in RELY-ABLE continued to receive the same dose of dabigatran as the original trial, with 2,937 patients using dabigatran 150 mg twice daily and 2,914 receiving 110 mg twice daily. There was no warfarin comparator group in the extension study. The median duration of followup was 4.3 years from the beginning of RE-LY to the end of RELY-ABLE, with the extension trial providing an additional 2.3 years of follow-up. The results from RELY-ABLE showed that the rates of ischemic stroke were 1.15% per year for the 150-mg dose and 1.24% per year for the 110-mg dose, while incidence of hemorrhagic stroke was 0.13% per year and 0.14% per year, respectively, for those doses. In addition, rates of major bleeding were 3.74% per year for the 150-mg dose and 2.99% per year for the 110-mg dose, while rates of intracranial bleeding were 0.33% per year and 0.25% per year, respectively, for the two doses. These results were consistent with those observed in RELY. Patients in RELY-ABLE differed in several respects from those in the original trial, however, with continuing patients less likely to have permanent atrial fibrillation, heart failure, or a major clinical event during the RE-LY trial. "The results from the RELY-ABLE study are consistent with the excellent results we have seen in the RE-LY trial and strongly support the long-term safety profile and efficacy of Pradaxa for stroke prevention in atrial fibrillation," said Klaus Dugi, Boehringer-Ingelheim Senior Vice President of Medicine, in a news release. "Physicians can be confident in the sustained brain protection and treatment advantages offered by both doses of Pradaxa and can tailor their treatment according to patient needs, as these first long-term clinical data for a novel oral anticoagulant show." The safety associated with using dabigatran was further supported by an FDA safety communication released in early November, in which the agency concluded that bleeding rates associated with new use of dabigatran do not appear to be higher than bleeding rates associated with new use of warfarin. The agency assessed actual rates of gastrointestinal bleeding and intracranial hemorrhage for new users of dabigatran compared with new users of warfarin using insurance claims and administrative data from FDA's MiniSentinel pilot of the Sentinel Initiative. An assessment of these data showed that the combined incidence rate of gastrointestinal hemorrhage and intracranial hemorrhage events per 100,000 days at risk was 1.8 to 2.6 times higher for new users of warfarin than for new users of dabigatran. In addition, the incidence rate of gastrointestinal hemorrhage events only per 100,000 days at risk was 1.6 to 2.2 times higher for new users of warfarin than for new users of dabigatran, and the incidence rate of intracranial hemorrhage events only per 100,000 days at risk was 2.1 to 3.0 times higher with warfarin than with dabigatran. Based on these results, FDA concluded that the observed bleeding rates associated with new use of dabigatran do not appear to be higher than the bleeding rates associated with new use of warfarin. Impact on current practiceThis article provides only a snapshot of key trials presented at AHA. Based on the results of OPERA, FORWARD, UMPIRE, FLAX-PAD, and RELY-ABLE, there is no role for the use of omega-3 fatty acids to prevent atrial fibrillation, a fixed-dose combination tablet may enhance adherence, increased dietary intake of flaxseed may be a good option to reduce blood pressure, and dabigatran appears to be safe and efficacious when used long-term. This article provides only a snapshot of key trials presented at AHA. Based on the results of OPERA, FORWARD, UMPIRE, FLAX-PAD, and RELY-ABLE, there is no role for the use of omega-3 fatty acids to prevent atrial fibrillation, a fixed-dose combination tablet may enhance adherence, increased dietary intake of flaxseed may be a good option to reduce blood pressure, and dabigatran appears to be safe and efficacious when used long-term.