Conflict of interest: None declared.
The Secondary Prevention of Small Subcortical Strokes (SPS3) study
Article first published online: 26 JAN 2011
© 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization
International Journal of Stroke
Volume 6, Issue 2, pages 164–175, April 2011
How to Cite
Benavente, O. R., White, C. L., Pearce, L., Pergola, P., Roldan, A., Benavente, M.-F., Coffey, C., McClure, L. A., Szychowski, J. M., Conwit, R., Heberling, P. A., Howard, G., Bazan, C., Vidal-Pergola, G., Talbert, R., Hart, R. G. and for the SPS3 Investigators (2011), The Secondary Prevention of Small Subcortical Strokes (SPS3) study. International Journal of Stroke, 6: 164–175. doi: 10.1111/j.1747-4949.2010.00573.x
Funding: SPS3 is an investigator initiated study funded by a cooperative agreement from the National Institute of Neurological Disorders and Stroke of United States (Grant #2 U01 NS38529-04A1). Together with members of the SPS3 Executive and Steering Committees, NINDS project officers directly participate in the execution of the study and oversee the progress. The clopidogrel and matching placebo have been donated by Sanofi-Aventis and Bristol-Myers Squibb. Neither company has any involvement with the design, execution, or analysis of the trial.
- Issue published online: 4 MAR 2011
- Article first published online: 26 JAN 2011
- antiplatelet therapy;
- lacunar stroke;
- randomised clinical trial;
Background Small subcortical strokes, also known as lacunar strokes, comprise more than 25% of brain infarcts, and the underlying vasculopathy is the most common cause of vascular cognitive impairment. How to optimally prevent stroke recurrence and cognitive decline in S3 patients is unclear. The aim of the Secondary Prevention of Small Subcortical Strokes study (Trial registration: NCT00059306) is to define strategies for reducing stroke recurrence, cognitive decline, and major vascular events.
Methods Secondary Prevention of Small Subcortical Strokes is a randomised, multicentre clinical trial (n=3000) being conducted in seven countries, and sponsored by the US NINDS/NIH. Patients with symptomatic small subcortical strokes in the six-months before and an eligible lesion on magnetic resonance imaging are simultaneously randomised, in a 2 × 2 factorial design, to antiplatelet therapy – 325 mg aspirin daily plus 75 mg clopidogrel daily, vs. 325 mg aspirin daily plus placebo, double-blind – and to one of two levels of systolic blood pressure targets –‘intensive’ (<130 mmHg) vs. ‘usual’ (130–149 mmHg). Participants are followed for an average of four-years. Time to recurrent stroke (ischaemic or haemorrhagic) is the primary outcome and will be analysed separately for each intervention. The secondary outcomes are the rate of cognitive decline and major vascular events. The primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment.
Conclusions Secondary Prevention of Small Subcortical Strokes will address several important clinical and scientific questions by testing two interventions in patients with recent magnetic resonance imaging-defined lacunar infarcts, which are likely due to small vessel disease. The results will inform the management of millions of patients with this common vascular disorder.