Almost all efficacious stroke treatments confer moderate-to-large benefits, but not staggeringly huge benefits. However, moderate treatment effects can be clinically very worthwhile for the patient. To detect moderate-large treatment benefits, trials must avoid bias and random error. Studies with weak designs (personal experience, observational studies with historical controls, and observational studies with concurrent, non-randomized controls) will not sufficiently control bias and random error to enable reliable discrimination of a true moderate-to-large benefit from false positives and false negatives. Randomized clinical trials are required. 'Ingredients' for a good trial – Proper randomization and concealment of allocation (i.e. clinician cannot have foreknowledge of next treatment allocation)/Outcome evaluation blind to the allocated treatment/Analysis by allocated treatment (including all randomized patients: intention-to-treat)/Large numbers of major outcomes and correspondingly narrow CIs/Conclusion based on pre-specified primary hypothesis and outcome/Chief emphasis on findings in overall study population. Advantages of systematic reviews (over traditional unsystematic, narrative reviews) – Use explicit, well-developed methods to reduce bias/Summarize large amounts of data explicitly/Provide all available data/Increase statistical power and precision/Look for consistencies/inconsistencies/Improve generalizability. Cochrane Reviews – Generally higher quality than other systematic reviews/Periodically updated/Available over internet/Abstracts available free of charge/Full reviews available free of charge in over 100 low- and middle-income countries

Long-term (>1 year) single antiplatelet therapy with aspirin is effective in reducing the risk of any early recurrent stroke by about one-sixth compared with no antiplatelet therapy. Clopidogrel monotherapy is marginally but significantly more effective than aspirin in reducing major vascular events. Cilostazol is also more effective than aspirin in Asian patients, and its therapeutic efficacy may be augmented by the addition of probucol in patients with ischaemic stroke and high risk of cerebral haemorrhage. The safety and effectiveness of cilostazol in non-Asian patients is not known. Prasugrel monotherapy (3.75 mg daily) is not non-inferior to clopidogrel monotherapy among Japanese patients with non-cardioembolic ischaemic stroke. Dual antiplatelet therapy with aspirin and extended-release dipyridamole is more effective than aspirin monotherapy and equally effective as clopidogrel monotherapy in preventing recurrent stroke. Dual antiplatelet therapy with aspirin and clopidogrel is more effective than aspirin monotherapy in preventing recurrent ischaemic stroke and myocardial infarction in high vascular risk patients, but it also increases the risk of major bleeding which may offset its benefits. Dual antiplatelet therapy with cilostazol added to aspirin or clopidogrel is more effective, and as safe as, aspirin or clopidogrel monotherapy in Japanese patients with non-cardioembolic ischaemic stroke.

Cardiogenic embolism is a common cause of recurrent ischaemic stroke. The cardiac source of embolism is usually the left atrial appendage and atrium due to atrial fibrillation (AF). Other sources include the left ventricle, heart valves and venous system or right atrium, via a patent foramen ovale.The most effective thromboprophylactic is oral anticoagulation, which reduces the risk of recurrent stroke by about two thirds, compared to no anticoagulation. Four target-specific, direct-acting non-vitamin K antagonist oral anticoagulants (NOACs) – the direct thrombin inhibitor dabigatran etexilate, and the factor Xa inhibitors rivaroxaban, apixaban and edoxaban – are at least as efficacious and safe as warfarin, and apixaban is superior to, and as safe as, aspirin, for preventing stroke among patients with AF. Other potential stroke prevention strategies include left atrial appendage occlusion for patients with AF in whom anticoagulation is contraindicated, anticoagulation for left ventricular thrombus and prosthetic heart valves, antibiotics +/– valve surgery for infective endocarditis, and transcatheter device closure of a symptomatic patent foramen ovale.

In the year 2010, an estimated 16.9 million strokes occurred worldwide at an incidence rate of 258 per 100,000 persons per year. Approximately 70% of these strokes occurred in low- and middle-income countries. The 16.9 million incident strokes were added to a pool of 33 million prevalent stroke survivors. There were 5.9 million deaths and 102 million disability-adjusted life-years (DALYs) lost due to stroke in 2010, making stroke the second leading cause of death and the third leading cause of DALYs worldwide. In the preceding two decades, between 1990 and 2010, the incidence rate of stroke remained stable but the absolute number of incident strokes increased by 68%, the prevalence rate increased modestly yet the absolute number of stroke survivors nearly doubled, the rate of DALYs lost due to stroke decreased but the absolute number of DALYs lost increased by 12%, and the mortality rate fell but the absolute number of stroke-related deaths increased by 26%. Most of the burden of stroke is in low-income and middle-income countries, which bear 63% of incident ischaemic strokes and 80% of haemorrhagic strokes. The average age of incident ischaemic and haemorrhagic strokes was 6 years younger in low- and middle– than high–income countries.