Jacob A Udell1, Marc P Bonaca2, Jean-Philippe Collet3, A Michael Lincoff4, Dean J Kereiakes5, Francesco Costa6, Cheol Whan Lee7, Laura Mauri8, Marco Valgimigli9, Seung-Jung Park7, Gilles Montalescot3, Marc S Sabatine2, Eugene Braunwald2, Deepak L Bhatt10. 1. Peter Munk Cardiac Centre and Cardiovascular Division, University Health Network, Heart and Stroke Richard Lewar Centre of Excellence, University of Toronto, 76 Grenville Street, Toronto, Canada ON M5S 1B1 Women's College Research Institute and Cardiovascular Division, Department of Medicine, Women's College Hospital, University of Toronto, Toronto, Canada jay.udell@utoronto.ca dlbhattmd@post.harvard.edu. 2. TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. 3. ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France. 4. Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH, USA. 5. The Christ Hospital Heart and Vascular Center and The Lindner Center for Research and Education at the Christ Hospital, Cincinnati, OH, USA. 6. Thoraxcenter, Erasmus Medical Center, Rotterdam 3015 CE, The Netherlands. 7. The Heart Institute, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. 8. Harvard Clinical Research Institute and Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 9. Thoraxcenter, Erasmus Medical Center, Rotterdam 3015 CE, The Netherlands University Hospital of Bern, Bern, Switzerland. 10. TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA jay.udell@utoronto.ca dlbhattmd@post.harvard.edu.
Abstract
AIMS: Recent trials have examined the effect of prolonged dual antiplatelet therapy (DAPT) in a variety of patient populations, with heterogeneous results regarding benefit and safety, specifically with regard to cardiovascular and non-cardiovascular mortality. We performed a meta-analysis of randomized trials comparing more than a year of DAPT with aspirin alone in high-risk patients with a history of prior myocardial infarction (MI). METHODS AND RESULTS: A total of 33 435 patients were followed over a mean 31 months among one trial of patients with prior MI (63.3% of total) and five trials with a subgroup of patients that presented with, or had a history of, a prior MI (36.7% of total). Extended DAPT decreased the risk of major adverse cardiovascular events compared with aspirin alone (6.4 vs. 7.5%; risk ratio, RR 0.78, 95% confidence intervals, CI, 0.67-0.90; P = 0.001) and reduced cardiovascular death (2.3 vs. 2.6%; RR 0.85, 95% CI 0.74-0.98; P = 0.03), with no increase in non-cardiovascular death (RR 1.03, 95% CI 0.86-1.23; P = 0.76). The resultant effect on all-cause mortality was an RR of 0.92 (95% CI 0.83-1.03; P = 0.13). Extended DAPT also reduced MI (RR 0.70, 95% CI 0.55-0.88; P = 0.003), stroke (RR 0.81, 95% CI 0.68-0.97; P = 0.02), and stent thrombosis (RR 0.50, 95% CI 0.28-0.89; P = 0.02). There was an increased risk of major bleeding (1.85 vs. 1.09%; RR 1.73, 95% CI 1.19-2.50; P = 0.004) but not fatal bleeding (0.14 vs. 0.17%; RR 0.91, 95% CI 0.53-1.58; P = 0.75). CONCLUSION: Compared with aspirin alone, DAPT beyond 1 year among stabilized high-risk patients with prior MI decreases ischaemic events, including significant reductions in the individual endpoints of cardiovascular death, recurrent MI, and stroke. Dual antiplatelet therapy beyond 1 year increases major bleeding, but not fatal bleeding or non-cardiovascular death. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Recent trials have examined the effect of prolonged dual antiplatelet therapy (DAPT) in a variety of patient populations, with heterogeneous results regarding benefit and safety, specifically with regard to cardiovascular and non-cardiovascular mortality. We performed a meta-analysis of randomized trials comparing more than a year of DAPT with aspirin alone in high-risk patients with a history of prior myocardial infarction (MI). METHODS AND RESULTS: A total of 33 435 patients were followed over a mean 31 months among one trial of patients with prior MI (63.3% of total) and five trials with a subgroup of patients that presented with, or had a history of, a prior MI (36.7% of total). Extended DAPT decreased the risk of major adverse cardiovascular events compared with aspirin alone (6.4 vs. 7.5%; risk ratio, RR 0.78, 95% confidence intervals, CI, 0.67-0.90; P = 0.001) and reduced cardiovascular death (2.3 vs. 2.6%; RR 0.85, 95% CI 0.74-0.98; P = 0.03), with no increase in non-cardiovascular death (RR 1.03, 95% CI 0.86-1.23; P = 0.76). The resultant effect on all-cause mortality was an RR of 0.92 (95% CI 0.83-1.03; P = 0.13). Extended DAPT also reduced MI (RR 0.70, 95% CI 0.55-0.88; P = 0.003), stroke (RR 0.81, 95% CI 0.68-0.97; P = 0.02), and stent thrombosis (RR 0.50, 95% CI 0.28-0.89; P = 0.02). There was an increased risk of major bleeding (1.85 vs. 1.09%; RR 1.73, 95% CI 1.19-2.50; P = 0.004) but not fatal bleeding (0.14 vs. 0.17%; RR 0.91, 95% CI 0.53-1.58; P = 0.75). CONCLUSION: Compared with aspirin alone, DAPT beyond 1 year among stabilized high-risk patients with prior MI decreases ischaemic events, including significant reductions in the individual endpoints of cardiovascular death, recurrent MI, and stroke. Dual antiplatelet therapy beyond 1 year increases major bleeding, but not fatal bleeding or non-cardiovascular death. Published on behalf of the European Society of Cardiology. All rights reserved.