Participation by patients from low- and middle-income countries (LMICs) in trial evidence supporting secondary stroke prevention guideline recommendations

Background: One out of every four strokes is a highly preventable recurrent stroke. However, while low-andmiddle-income countries (LMICs) experience a disproportionate global burden of stroke, individuals in these regions seldomly participate in pivotal clinical trials, which form the basis for international expert consensus guideline recommendations. Objective: To evaluate a contemporary and globally prominent expert consensus secondary stroke prevention guideline statement for the participation of clinical trial subjects recruited from LMICs in formulating key therapeutic recommendations. Methods: We examined the 2021 American Heart Association/American Stroke Association Guideline for the Prevention of Stroke in Patients with Stroke and TIA. All randomized controlled trials (RCTs) cited in the Guideline were independently reviewed by two authors for study populations and participating countries with a focus on trials for vascular risk factor control and management by underlying stroke mechanism. We also reviewed all cited systematic reviews and meta-analyses for the original RCTs. Results: Among 320 secondary stroke prevention clinical trials, 262 (82%) focused on vascular risk control addressing diabetes (n = 26), hypertension (n = 23), obstructive sleep apnea (n = 13), dyslipidaemia (n = 10), lifestyle (n = 188) and obesity (n = 2); and 58 focused on stroke mechanism management including atrial fibrillation (n = 10), large vessel atherosclerosis (n = 45) and small vessel disease (n = 3). Overall, 53 of 320 studies (16.6%) had contributions from LMICs ranging from 55.6% for dyslipidemia, 40.7% for diabetes, 26.1% for hypertension, 15.4% for OSA, 6.4% for lifestyle, 0% for obesity, and by mechanism: 60.0% for atrial fibrillation, 22.2% large vessel atherosclerosis and 33.3% for small vessel disease trials. Only 19 (5.9%) of the trials had participatory contributions from a country in sub-Saharan Africa (South Africa only). Conclusions: Compared to their global burden of stroke, LMICs are underrepresented in key clinical trials used in formulating a prominent global stroke prevention guideline. While current therapeutic recommendations are likely applicable to practice settings throughout the world, greater involvement of patients from LMIC settings will enhance the contextual relevance and generalizability of recommendations to these disparate populations.