Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials.
OBJECTIVE
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).


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).


CONCLUSIONS
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.
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.
Jacob A
JA
Udell
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Marc P
MP
Bonaca
ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France.
Jean-Philippe
JP
Collet
Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH, USA.
A Michael
AM
Lincoff
The Christ Hospital Heart and Vascular Center and The Lindner Center for Research and Education at the Christ Hospital, Cincinnati, OH, USA.
Dean J
DJ
Kereiakes
Thoraxcenter, Erasmus Medical Center, Rotterdam 3015 CE, The Netherlands.
Francesco
F
Costa
The Heart Institute, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Cheol Whan
CW
Lee
Harvard Clinical Research Institute and Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Laura
L
Mauri
Thoraxcenter, Erasmus Medical Center, Rotterdam 3015 CE, The Netherlands University Hospital of Bern, Bern, Switzerland.
Marco
M
Valgimigli
The Heart Institute, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Seung-Jung
SJ
Park
ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France.
Gilles
G
Montalescot
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Marc S
MS
Sabatine
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Eugene
E
Braunwald
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.
Deepak L
DL
Bhatt
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D006801:Humans; D008134:Long-Term Care; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D055502:Secondary Prevention / Q000379:methods; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome; D055815:Young Adult
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
Clopidogrel; Dual antiplatelet therapy; Myocardial infarction; Prasugrel; Stable coronary heart disease; Ticagrelor