Abstract 132: Disability and Enrollment in Secondary Stroke Prevention Trials: Evidence for a New Paradigm of Inclusion

Abstract

Background: Ischemic stroke secondary prevention trials have disproportionately enrolled participants with mild or no disability. The impact of this skew on trial event rates is unclear. Methods: We included participants with ischemic stroke in two secondary stroke prevention trials, PRoFESS and IRIS. The exposure was functional status at entry, defined as modified Rankin Scale (mRS) 0 vs. 1-2 vs. >2. The primary outcome was recurrent stroke (ischemic or hemorrhagic). The secondary outcome was a composite of major adverse cardiovascular events (MACE=stroke, myocardial infarction, heart failure, and vascular death). Results: The cohorts had 20,384 participants from PRoFESS and 3,374 from IRIS. The mean duration of follow-up was 2.4 years in PRoFESS and 3.8 years in IRIS. The rate of recurrent stroke in the mRS categories (0 vs. 1-2 vs. >2) was 7.2%, 8.7%, and 10.6% in PRoFESS and 6.2%, 9.1%, and 11.9% in IRIS (both p≤0.001). The rate of MACE in the mRS categories was 10.1%, 12.2%, and 17.3% in PRoFESS (p<0.001) and 10.6%, 13.3%, and 15.3% in IRIS (p=0.030). In both trials we saw consistent increases in the hazard ratio for recurrent stroke (Table 1) and MACE (Table 2) across mRS categories, after adjusting for potential confounders. There was no evidence that treatment effects differed across mRS categories (mRS by treatment interaction p>0.4). Conclusion: Secondary stroke prevention trial participants with higher levels of baseline disability have increased rates of recurrent stroke and MACE. By enrolling participants across the full range of disability, stroke trials would observe more recurrent stroke events, enhance statistical power, and improve generalizability of results.