Potent P2Y12Inhibitors in Men Versus Women: A Collaborative Meta-Analysis of Randomized Trials.
BACKGROUND
Sex-specific differences in response to antiplatelet therapies have been described. Whether women and men derive comparable benefit from intensification of antiplatelet therapy remains uncertain.


OBJECTIVE
The study investigated the efficacy and safety of the potent P2Y12inhibitors in patients with coronary artery disease.


METHODS
A collaborative sex-specific meta-analysis was conducted of phase III or IV randomized trials of potent P2Y12inhibitors, including prasugrel, ticagrelor, and intravenous cangrelor. Seven trials were included that enrolled a total of 24,494 women and 63,346 men. Major adverse cardiovascular events (MACE) were defined as the primary endpoint for each trial.


RESULTS
Potent P2Y12inhibitors significantly reduced the risk of MACE by 14% in women (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.78 to 0.94) and by 15% in men (HR: 0.85; 95% CI: 0.80 to 0.90; p interaction = 0.93). Treatment reduced the risk of myocardial infarction by 13% in women (HR: 0.87; 95% CI: 0.78 to 0.96) and 16% in men (HR: 0.84; 95% CI: 0.77 to 0.91; p interaction = 0.65), and the risk of stent thrombosis by 51% in women (HR: 0.49; 95% CI: 0.37 to 0.65) and 41% in men (HR: 0.59; 95% CI: 0.42 to 0.84; p interaction = 0.85). Directional consistency was seen for cardiovascular death in women (HR: 0.87; 95% CI: 0.76 to 1.01) and men (HR: 0.85; 95% CI: 0.77 to 0.95; p interaction = 0.86). The potent P2Y12inhibitors increased major bleeding in women (HR: 1.28; 95% CI: 0.87 to 1.88) and men (HR: 1.52; 95% CI: 1.12 to 2.07; p interaction = 0.62).


CONCLUSIONS
In randomized trials, the efficacy and safety of the potent P2Y12inhibitors were comparable between men and women. Given these data, sex should not influence patient selection for the administration of potent P2Y12inhibitors.
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Emily S
ES
Lau
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Eugene
E
Braunwald
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Sabina A
SA
Murphy
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Stephen D
SD
Wiviott
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Marc P
MP
Bonaca
Department of Cardiology, Århus University Hospital, Århus, Denmark.
Steen
S
Husted
Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Stefan K
SK
James
Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Lars
L
Wallentin
Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Hamburg, Germany; Department of Medicine, Nykoebing F Hospital, University of Southern Denmark, Odense, Denmark.
Peter
P
Clemmensen
Division of Cardiology, Duke Clinical Research Institute, Durham, North Carolina.
Matthew T
MT
Roe
Division of Cardiology, Duke Clinical Research Institute, Durham, North Carolina.
E Magnus
EM
Ohman
Department of Medicine, Stanford University, Stanford, California.
Robert A
RA
Harrington
Verily Life Sciences, Mountain View, California.
Jessica L
JL
Mega
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Deepak L
DL
Bhatt
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Marc S
MS
Sabatine
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: modonoghue@partners.org.
Michelle L
ML
O'Donoghue
D003324:Coronary Artery Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012727:Sex Characteristics; D016896:Treatment Outcome
D058921:Purinergic P2Y Receptor Antagonists
acute coronary syndrome; antiplatelet therapy; cangrelor; coronary artery disease; prasugrel; ticagrelor