Understanding the PRoFESS study for secondary stroke prevention

Abstract

The Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial is the largest secondary stroke prevention study completed to date. It compared extended-release dipyridamole plus aspirin (eDYP-ASA) versus clopidogrel and telmisartan versus antihypertensive regimens excluding angiotensin receptor blockers (ARBs). No statistical differences were found in either arm for the primary outcome of fatal or nonfatal stroke or prespecified secondary end points. eDYP-ASA also was associated with increases in major hemorrhagic events but not with statistical increases in combined rates of stroke recurrence or hemorrhage. Despite PRoFESS, the role of ARBs post stroke remains unclear, as concomitant angiotensin-converting enzyme inhibitor use in PRoFESS obscured whether just blood pressure lowering or renin-angiotensin system blockade is important. The resulting interpretation that eDYP-ASA is "not noninferior" has raised questions about how to interpret noninferiority analyses. Also, although the PRoFESS editorialists suggested that aspirin, the historical bystander control, was the "winner," a review of prior antiplatelet studies suggests that the benefits of aspirin, either as combination or monotherapy, are outweighed by its bleeding hazards. The benefits of clopidogrel or eDYP-ASA, compared with aspirin, are small but real, and both remain preferred agents in secondary stroke prevention.