ORLANDO, FLA. — An experimental clot-inhibiting drug didn’t improve outcomes for patients who experienced a sudden, dangerous reduction of blood flow to the heart, according to late-breaking research presented at the American Heart Association’s Scientific Sessions 2011.
The study is simultaneously published in the New England Journal of Medicine.
In the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA•CER) Study, researchers compared vorapaxar to a placebo in patients with non-ST-segment elevation acute coronary syndrome. These patients experience unstable angina or a non-STEMI heart attack, where a coronary artery is partially blocked, reducing blood flow to the heart.
Researchers enrolled 12,944 patients at 818 sites in 37 countries. All patients received the usual medical care for their condition, typically involving aspirin and clopidogrel (Plavix), as well as procedures such as catheterization, coronary stenting or surgery if indicated.
Half the participants also were given a 40-milligram initial dose followed by a 2.5-milligram daily dose of vorapaxar, the first in a new class of anti-platelet drugs, PAR-1 antagonists. The rest of the patients received a placebo.
Participants given vorapaxar were just as likely as those given placebo to experience at least one of five outcomes — cardiovascular-related death, heart attack, stroke, a new hospitalization for unstable angina or urgent revascularization. After two years of study, almost one in five patients in each group had such an outcome (18.5 percent vorapaxar vs. 19.9 percent placebo).
Researchers also found that the patients who received vorapaxar had more bleeding and had a three-fold increase in the risk of hemorrhagic stroke.
Patients on vorapaxar also had a 14.7 percent risk of cardiovascular death, heart attack or stroke, compared to 16 percent for patients given the placebo, a difference that was not statistically significant.
Researchers said there was discordance between these findings and their earlier Phase 2 study.
“The difference in the primary endpoint was more modest and the bleeding risk was higher than expected,” said Kenneth W. Mahaffey, M.D., lead author of the study and co-director of cardiovascular research at the Duke Clinical Research Institute in Durham, N.C. “Earlier studies of vorapaxar had not identified an excess bleeding risk, so these findings are surprising. More work is needed to understand the bleeding risk. Whether it’s related to the use of aspirin and clopidogrel in these patients or other factors need to be and will be examined carefully.”
“We were surprised and disappointed that TRA•CER failed to meet its primary endpoint,” said Robert Harrington, M.D., chair of the TRA•CER steering committee and director of the Duke Clinical Research Institute. “The lower incidence of cardiovascular death, heart attack or stroke with vorapaxar while not significant, is promising and we look forward to seeing the data from the next trial (TRA 2P TIMI 50) to better understand if or how to proceed with further development of vorapaxar.”
Co-authors are Pierluigi Tricoci, M.D., Ph.D.; Yuliya Lokhnygina, Ph.D.; Paul W. Armstrong, M.D.; Phillip E. Aylward, M.D.; Edmond Chen, M.D.; Claes Held, M.D., Ph.D.; Sergio Leonardi, M.D., M.H.S.; Ann Kilian; David J. Moliterno, M.D.; Tyrus L. Rorick, R.N.; John Strony, M.D.; Frans Van de Werf, M.D.; Lars Wallentin, M.D., Ph.D.; Harvey D. White, D.Sc.; and Robert A. Harrington, M.D., for the TRA•CER Steering Committee and TRA•CER investigators.
Disclosures are here: http://newsroom.heart.org/pr/aha/document/Disclosures_for_LBCT.xlsx.
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., funded the study.
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