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Stroke is a major global health concern, particularly among the elderly, who frequently present with multiple comorbidities, most notably cardiovascular diseases. Importantly, atrial fibrillation confers a nearly fivefold increase in stroke risk and accounts for up to one-quarter of ischemic strokes in older adults. Stroke is a neurological disease characterised by a strong cardiovascular interplay, and its multifactorial nature requires an integrated preventive approach. This review focuses on primary and secondary prevention in this population, with a frailty-informed perspective. We synthesise evidence on blood pressure control, lipid-lowering (including LDL-C targets), glycemic management, and antithrombotic strategies-particularly oral anticoagulation for atrial fibrillation-as well as the role of frailty indices in guiding individualised risk-benefit decisions. We also discuss practical care pathways, including structured post-discharge programs, continuity of care, and the need for multidisciplinary collaboration involving cardiologists, neurologists, and primary care. We highlight how frailty indices refine risk-benefit assessments without justifying therapeutic nihilism, and how sex- and age-related factors shape treatment effectiveness and safety. By narrowing scope and emphasising practical, multidisciplinary prevention strategies, this review aims to support clinicians in reducing recurrent events, disability, and mortality in very old patients. Future work should prioritise pragmatic trials, including those involving the oldest old and the use of standardised frailty metrics, to inform prevention decisions.