Association of aspirin dose and vorapaxar safety and efficacy in patients with
non-ST-segment elevation acute coronary syndrome (from the TRACER Trial).
Author(s): Mahaffey KW(1), Huang Z(2), Wallentin L(3), Storey RF(4), Jennings LK(5), Tricoci
P(2), White HD(6), Armstrong PW(7), Aylward PE(8), Moliterno DJ(9), Van de Werf
F(10), Chen E(11), Leonardi S(12), Rorick T(2), Held C(3), Strony J(13),
Harrington RA(14).
Affiliation(s): Author information:
(1)Department of Medicine, Stanford University, Stanford, California. Electronic
address: kenneth.mahaffey@stanford.edu.
(2)Duke Clinical Research Institute, Durham, North Carolina.
(3)Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala,
Sweden.
(4)Department of Cardiovascular Science, University of Sheffield, Sheffield, United
Kingdom.
(5)University of Tennessee Health Science Center, Memphis, Tennessee; CirQuest Labs,
LLC, Memphis, Tennessee.
(6)Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
(7)Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada.
(8)South Australian Health and Medical Research Institute, Flinders University and
Medical Centre, Adelaide, South Australia, Australia.
(9)Gill Heart Institute and Division of Cardiovascular Medicine, University of
Kentucky, Lexington, Kentucky.
(10)Department of Cardiology, University of Leuven, Leuven, Belgium.
(11)Global Clinical Development, Bayer HealthCare Pharmaceuticals Inc., Whippany, New
Jersey.
(12)Duke Clinical Research Institute, Durham, North Carolina; Fondazione IRCCS
Policlinico San Matteo, Pavia, Italy.
(13)Merck, Whitehouse Station, New Jersey.
(14)Department of Medicine, Stanford University, Stanford, California.
Publication date & source: 2014, Am J Cardiol. , 113(6):936-44
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.
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