Mark J. Alberts, MD


June 18, 2012

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Hello. I am Dr. Mark Alberts, professor of neurology at Northwestern University in Chicago. Welcome to this Medscape stroke blog update. Today, I want to talk to you about a new medication called vorapaxar, a novel antiplatelet agent with a unique mechanism of action. Vorapaxar works by inhibiting the thrombin receptor on platelets.

Vorapaxar was studied in a very large prospective randomized trial called the TIMI 50 or TRA 2P study.[1] This study randomly assigned more than 26,000 patients with stable coronary disease, ischemic stroke, or peripheral artery disease to receive either vorapaxar plus standard antiplatelet therapy -- whatever that might be for the particular patient population -- or placebo plus standard antiplatelet therapy, again whatever that might be.

TIMI 50 demonstrated a statistically significant benefit for vorapaxar vs placebo for the endpoints of stroke, myocardial infarction (MI), and vascular death; the absolute risk reduction was a slightly more than 1% in favor of vorapaxar vs placebo. However, this benefit was counterweighted by almost a doubling of serious hemorrhagic events in patients treated with vorapaxar vs placebo.

We have seen in other studies that adding more antiplatelet therapy tends to increase the risk for bleeding complications. However, the rate of serious bleeding events, particularly intracranial hemorrhage, was driven by the subpopulation of study patients with previous stroke. If you take that group out of the equation, then the difference in the rate of serious bleeding events with vorapaxar vs placebo is much narrower. For the patients enrolled in the study with previous coronary artery disease, particularly those with a history of MI, vorapaxar provided obvious benefit.

Thus, these are mixed results. We will have to see what the regulators decide to do about it, but perhaps this will become another antiplatelet option with a unique mechanism that we can use for our patients with ischemic disease in the heart, brain, or leg.

In the interest of full disclosure, my site at Northwestern University was involved in the TIMI 50 study, and I am a member of the steering committee and have been compensated for that. These results are published in the New England Journal of Medicine, and you are welcome to read them at your leisure. Thank you very much for your attention, and I hope you have a good day.


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