Aspirin for secondary prevention after stroke of unknown etiology in resource-limited settings: a decision analysis

Background: Seventy-one percent of worldwide stroke mortality and 77.5% of worldwide stroke disability-adjusted life years (DALYs) lost occur in lowand middle-income countries (LMIC). This disproportionate burden of stroke in LMIC is due to resource limitations in both prevention and treatment. In addition to risk factor modification, aspirin is an inexpensive and effective medication for secondary stroke prevention. However, only 3.8% of patients with prior stroke in low-income countries take antiplatelet agents, compared to 53.1% in high-income countries. One reason for this is that without access to CT to distinguish ischemic stroke (IS) from intracerebral hemorrhage (ICH), clinicians must balance presumed risks of aspirin administration in patients with potential ICH against potential benefits of secondary prevention in patients with possible IS. In order to assist clinicians practicing in resource-limited settings, we conducted a decision analysis to determine the impact of administering aspirin as long-term secondary preventive therapy to all patients after stroke when CT is not available to distinguish IS from ICH. Methods: We used a Markov state transition model to evaluate the potential outcomes of two strategies for long-term secondary prevention after stroke of undetermined etiology: administering aspirin to all patients versus not administering aspirin to any patients. Data on the risks and benefits of aspirin use after IS and ICH were obtained from meta-analyses and large series. Sensitivity analyses were performed across the worldwide reported range of the proportion of strokes due to ICH and the 95% confidence intervals of aspirin-associated relative risks in patients with ICH. Findings: For patients with stroke of unknown etiology, long-term aspirinwas the preferred treatment strategy across theworldwide reported range of the proportion of strokes due to ICH. At 34% of strokes due to ICH (the highest proportion reported in a large epidemiologic study), the benefit of aspirin remained beyond the upper bounds of the 95% confidence intervals of aspirin-associated post-ICH relative risks most concerning to clinicians (ICH recurrence risk andmortality risk if ICHrecurs on aspirin). Based on the estimated11,590,204 strokes inLMIC in2010, ourmodel predicts that aspirin therapy for secondary stroke prevention in all patients in these countries could lead to an estimated yearly decrease of 84,492 recurrent strokes and 4,056 stroke-related mortalities. Interpretation: The concern that the risks of aspirin in patients with stroke of unknown etiology could outweigh the benefits is not supported by our model, which predicts that aspirin for secondary prevention after stroke of undetermined etiology could lead to decreased stroke-related mortality and stroke recurrence. In the absence of a clinical trial to test this approach empirically, clinical decisions still require patient-specific assessment of risk and benefit. Funding: None. Abstract #: 01NCD001