Stroke Minimization through Additive Anti-atherosclerotic agents in Routine Treatment (SMAART) II: Rationale for a multi-country polypill Phase 3 trial in sub-Saharan Africa

• The contribution of Africa to the global burden of stroke is substantial • Hypertension and dyslipidemia are targets for risk mitigation after stroke • The effectiveness of cardiovascular polypill for secondary prevention after stroke remains to be tested in large RCTs • The polypill contains fixed doses of three antihypertensives, a statin and an antiplatelet and will be taken daily for 24 months • This paper provides a rationale for a hybrid RCT to be conducted in 3 African countries testing the efficacy and implementation outcomes of a polypill for secondary prevention after a non-cardioembolic ischemic stroke Global estimates suggest that sub-Saharan Africa (SSA) now has the highest incidence, prevalence, and worst survival outcomes of stroke. Fixed-dose combination pills, also known as “polypills”, containing generic drugs: Aspirin, a statin, and blood pressure (BP) lowering medications may be a viable low-cost avenue to broadly improve medication adherence and consequently reduce further disability or death on a large scale among stroke survivors in SSA. The Stroke Minimization through Additive Anti-atherosclerotic agents in Routine Treatment II ( SMAART-II ) study seeks to deploy a hybrid study design to 1) demonstrate the efficacy of a polypill (Polycap ®) containing fixed doses of antihypertensives, a statin, and antiplatelet therapy taken as two capsules , once daily orally in reducing composite vascular risk over 24 months vs. usual care among 1,000 recent ischemic stroke patients encountered at primary and tertiary hospitals in Benin, Nigeria and Tanzania; 2) develop an implementation strategy for routine integration and policy adoption of polypill for post-stroke cardiovascular risk reduction in an under-resourced system burdened by suboptimal care and outcomes . SMAART II will establish the definitive efficacy and safety of the polypill to improve meaningful post-stroke global risk factor control across several sites, across diverse healthcare settings, beyond tertiary level care, and over a longer period. In addition to assessing clinical outcomes, SMAART II will assess implementation outcomes such as adoption, acceptability, cost, pertinent to uptake of the polypill strategy in the three proposed African countries to inform policy.