intensifying platelet inhibition in patients with lacunar stroke does not help

so, just after i sent out the neurology association recommendations on anticoagulation for nonvalvular atrial fibrillation, i found this article -- which looked at patients who had lacunar strokes while already on aspirin to see if adding clopidogrel helped (see stroke clopid plus asa not help if on asa neuro 2014 in dropbox, or DOI 10.1212/WNL.0000000000000076).  this is a post-hoc analysis of patients with aspirin failure and recent lacunar stroke in the larger SPS3 study (secondary prevention of small subcortical strokes trial).

--SPS3 involved 3000 patients with recent (<180d) symptomatic lacunar stroke with ipsilateral carotid artery disease not amenable to surgery, then all received aspirin 325mg/d and were randomly assigned to get additional clopidogrel vs placebo. this present study looked at the group (secondary analysis) of 838 patients who had been on aspirin prior to the lacunar stroke (the aspirin failure group) to see if those put on aspirin plus clopidogrel did better than those continued on aspirin alone. followup 3.5 years
--results: no diff in recurrent stroke if on aspirin or both drugs, each with 3% annual stroke rates. all-cause mortality in combo group was higher than in aspirin alone group (HR 2.13), along with doubling of hemorrhagic risk of GI bleeding
--this lack of protective effect of adding on clopidogrel was evident even in this subgroup of "aspirin failure", which had a 30% higher risk profile for ischemic stroke.

so, i think this study does add to clinical management, though the results were a post-hoc analysis.  the not-so-uncommon clinical conundrum is the patient already on aspirin who has a stroke: what should we do? an appealing option was to intensify the anti-platelet attack, but this study suggests otherwise.  studies have found that the combo aspirin/dipyridamole or using clopidogrel alone seems to be somewhat more effective in secondary prevention of stroke than aspirin by itself, but to my knowledge, no one has looked at the cohort of "aspirin failures" with these meds (though probably best choice in patient who would not benefit from surgical intervention would be switching aspirin to one of these 2 therapies).

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