A systematic review of advances and challenges in stroke prevention in sickle cell disease since the STOP trials

Background. Stroke is among the most disabling complications of sickle cell disease (SCD) in both children and adults. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) and its successor (STOP II) established transcranial Doppler (TCD) screening with chronic transfusion as the foundation of primary stroke prevention. More than two decades later, the central problem has shifted from establishing efficacy to achieving equitable implementation, and the evidence base for adults and for newer disease-modifying agents remains comparatively limited. Objectives. To systematically identify, appraise and synthesise evidence on stroke prevention in SCD generated during and after the STOP era; to characterise advances in diagnosis and therapy; to examine barriers to implementation, with particular attention to sub-Saharan Africa; and to identify priorities for future research.