The goal of SPS3 was to learn if combination antiplatelet therapy (aspirin and clopidogrel) is more effective than aspirin alone for the prevention of recurrent stroke and cognitive decline, and if intensive blood pressure control is associated with fewer recurrent strokes and cognitive decline.  SPS3 planned to recruit 3000 participants with a qualifying initial stroke and randomize, in a factorial fashion, to one of two antiplatelet management regimens (aspirin+clopidogrel vs aspirin+placebo) and one of two hypertension management regimens (treatment to target of SBP 130-149 or <130 mmHg).  The DSMB recommended terminating the antiplatelet arm of the study early due to an imbalance of overall and major non-CNS hemorrhagic serious adverse events and total deaths in the investigational antiplatelet combination of aspirin + clopidogrel and an interim statistical analysis that demonstrated futility in the investigational antiplatelet arm. It was recommended that patients be continued on standard care of aspirin monotherapy until their study close-out visit.

• 82 international sites
• 3020 participants randomized
• 2x2 factorial RCT
• NINDS funded, NCT: NCT00059306
• Clinicaltrials.gov website: https://clinicaltrials.gov/study/NCT00059306?term=NCT00059306&rank=1