A New Antiplatelet Drug

The September 15, 2014 issue of The Medical Letter includes an article on vorapaxar (Zontivity), an antiplatelet drug that inhibits aggregation of platelets by interfering with the platelet-activating effects of thrombin, a mechanism of action that sets it apart from aspirin and the thienopyridines clopidogrel and prasugrel. Two clinical trials looked at whether adding it to aspirin and/or clopidogrel could improve clinical outcomes without causing an unacceptable increase in bleeding.

The results, published in 2 articles in The New England Journal of Medicine, were mixed. The first trial (TRACER), in patients with acute coronary syndromes, showed no benefit for vorapaxar plus standard of care over placebo in reducing death from cardiovascular causes, myocardial infarction, or stroke, but the risk of serious bleeding, including intracranial hemorrhage, was significantly increased in vorapaxar-treated patients. This trial was halted early by the data and safety monitoring board because of this bleeding risk.

In the second trial of the drug (TRAP 2°P – TIMI 50), which apparently was the basis for its FDA approval, the addition of vorapaxar to standard therapy in patients with a history of atherosclerosis reduced the risk of cardiovascular death, myocardial infarction, or stroke, especially in patients with a history of myocardial infarction. The data and safety monitoring board was the same in both trials, which were going on simultaneously. When the board decided to halt the TRACER trial early, they also recommended discontinuation of vorapaxar in the TRAP 2°P – TIMI 50 trial in patients with a history of stroke because of an increased risk of intracranial hemorrhage in those patients. The publication of the trial included a separate analysis confined to patients who did not have a history of stroke, and as would be expected, they had a lower incidence of intracranial bleeding associated with vorapaxar than the group as a whole, but it still was significantly higher than the incidence with placebo.

For a more complete analysis of the results in these studies and others, watch for the next issue of The Medical Letter.

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