Peggy Nguyen, MD
Despite the multitude of clinical trials evaluating anti-platelet therapies for recurrent stroke, there are still no clear answers on the optimal regimen for patients who have “failed aspirin.” Here, the authors use a nationwide stroke registry to analyze outcomes of patients who have suffered a non-cardioembolic stroke while on aspirin, looking at three different arms: (1) those who were maintained on aspirin after their stroke, (2) those who were switched to a different anti-platelet agent, the most common being clopidogrel and (3) those who had a second anti-platelet agent added on to aspirin, again, commonly clopidogrel.
Of note, baseline characteristics were different among the three groups. For example, index large artery atherosclerosis strokes were much more common in the dual anti-platelet therapy group compared to the mono-aspirin group, while other etiologies and undetermined causes were much more common in the mono-aspirin group. In general, however, results were suggestive of benefit with alternative antiplatelet therapies when someone has had an aspirin failure, more so for dual antiplatelet therapy. Patients had less composite events (combination of stroke, MI, and all-cause mortality) when they were switched to dual-antiplatelet therapy compared to the other regimens; similarly, those who were switched to a different anti-platelet therapy did better than those maintained on aspirin. In respect to ischemic stroke recurrence alone, however, switching to another antiplatelet agent did not reduce stroke recurrence, although the addition of another antiplatelet therapy did.
Does this mean patients should be switched to dual antiplatelet therapy if they have failed aspirin monotherapy? Perhaps. The CHANCE trial (NEJM, 2013) showed benefit of short-term dual antiplatelet therapy in certain patients and patients in the SAMMPRIS trial (NEJM, 2011) did quite well on dual antiplatelet therapy (although antiplatelet regimen was not the focus of that trial). Although clopidogrel was the most common alternative antiplatelet medication used, some patients were on cilostazol, a medication which is more widely used in Asian countries than in the United States, so there was not uniformity in the regimens chosen. A randomized controlled trial may be the way to go to provide more definitive answers.