Stroke Minimization through Additive Anti-atherosclerotic Agents in Routine Treatment II Study - Global estimates suggest that sub-Saharan Africa (SSA) now has the highest incidence and prevalence of stroke and the worst survival outcomes from stroke in the world. Current projections are that the already overwhelming burden of strokes and other cardiovascular diseases (CVDs) in Africa will continue to escalate over the coming decades as traditional vascular risk factors burgeon in these populations. Indeed, hypertension and dyslipidemia are the top 2 modifiable risk factors for stroke in Africa with population attributable fractions of 90.2% and 35.8%, respectively, positioning them as prime targets for secondary risk reduction after stroke. Identifying strategies to reduce vascular risk in Low-and Middle-Income Countries (LMICs) will meet a global goal of reducing chronic disease death rates by an additional 2% per year, with only a moderate rise in health expenditures. Ghana is a LMIC in SSA with a profound lack of human resources for health care coordination for stroke survivors, especially in the implementation of evidence-based secondary prevention therapies. Fixed-dose combination pills, also known as “polypills”, containing generic drugs: aspirin, a statin, and blood pressure (BP) lowering medication(s), 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. Therefore, the overall objective of Stroke Minimization through Additive Anti-atherosclerotic agents in Routine Treatment II (SMAART-II) study is 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 500 recent stroke patients encountered at 12 hospitals in Ghana; 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 is premised on the feasibility and relative safety of the Polycap ® for ischemic stroke among Ghanaians in a single center trial (SMAART-I) conducted with the support of an R21 grant (NS103752) from the NIH Global Brain Disorders program. We now seek to test the definitive efficacy and safety of the polypill to improve meaningful post-stroke global risk factor control in a larger sample, across several sites, across diverse health care 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 Ghana to inform policy. Regardless of its outcome, findings from SMAART-II will contribute meaningful information from the African perspective to inform the formulation of guidelines for global adoption of polypills into routine care for secondary CVD risk prevention by international bodies such as the World Health Organization.