Association of aspirin dose and vorapaxar safety and efficacy in patients with non-ST-segment elevation acute coronary syndrome (from the TRACER Trial).
Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial compared vorapaxar and placebo in 12,944 high-risk patients with non-ST-segment elevation acute coronary syndrome. We explored aspirin (ASA) use and its association with outcomes. Kaplan-Meier event rates were compared in groups defined by ASA dose (low, medium, and high). Landmark analyses with covariate adjustment were performed for 0 to 30, 31 to 180, and 181 to 365 days. Of 12,515 participants, 7,523, 1,049, and 3,943 participants were treated with low-, medium-, and high-dose ASA at baseline, respectively. Participants enrolled in North America versus elsewhere were more often treated with a high dose at baseline (66% vs 19%) and discharge (60% vs 3%). Unadjusted cardiovascular death, myocardial infarction, stroke, hospitalization for ischemia, or urgent revascularization event rates tended to be higher with higher baseline ASA (18.45% low, 19.13% medium, and 20.27% high; p for trend = 0.15573). Unadjusted and adjusted hazard ratios (95% confidence intervals) for effect of vorapaxar on cardiovascular (unadjusted p for interaction = 0.065; adjusted p for interaction = 0.140) and bleeding (unadjusted p for interaction = 0.915; adjusted p for interaction = 0.954) outcomes were similar across groups. Landmark analyses showed similar safety and efficacy outcomes with vorapaxar and placebo by ASA dose at each time point except for 0 to 30 days, when vorapaxar tended to be worse for efficacy (hazard ratio 1.13, 95% confidence interval 0.89 to 1.44, p for interaction = 0.0157). In conclusion, most TRACER participants were treated with low-dose ASA, although a high dose was common in North America. High-dose participants tended to have higher rates of ischemic and bleeding outcomes. Although formal statistical testing did not reveal heterogeneity in vorapaxar's effect across dose subgroups, consistent trends support use of low-dose ASA with other antiplatelet therapies.
Department of Medicine, Stanford University, Stanford, California. Electronic address: kenneth.mahaffey@stanford.edu.
Kenneth W
KW
Mahaffey
Duke Clinical Research Institute, Durham, North Carolina.
Zhen
Z
Huang
Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala, Sweden.
Lars
L
Wallentin
Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
Robert F
RF
Storey
University of Tennessee Health Science Center, Memphis, Tennessee; CirQuest Labs, LLC, Memphis, Tennessee.
Lisa K
LK
Jennings
Duke Clinical Research Institute, Durham, North Carolina.
Pierluigi
P
Tricoci
Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
Harvey D
HD
White
Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada.
Paul W
PW
Armstrong
South Australian Health and Medical Research Institute, Flinders University and Medical Centre, Adelaide, South Australia, Australia.
Philip E
PE
Aylward
Gill Heart Institute and Division of Cardiovascular Medicine, University of Kentucky, Lexington, Kentucky.
David J
DJ
Moliterno
Department of Cardiology, University of Leuven, Leuven, Belgium.
Frans
F
Van de Werf
Global Clinical Development, Bayer HealthCare Pharmaceuticals Inc., Whippany, New Jersey.
Edmond
E
Chen
Duke Clinical Research Institute, Durham, North Carolina; Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Sergio
S
Leonardi
Duke Clinical Research Institute, Durham, North Carolina.
Tyrus
T
Rorick
Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala, Sweden.
Claes
C
Held
Merck, Whitehouse Station, New Jersey.
John
J
Strony
Department of Medicine, Stanford University, Stanford, California.
Robert A
RA
Harrington
D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D000284:Administration, Oral; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007783:Lactones / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage*; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D018179:Receptors, Thrombin; D001241:Aspirin; C530299:vorapaxar