ABSTRACT NUMBER: ESOC2026A276 IMPACT OF FRAILTY ON EFFECTS OF ANTIHYPERTENSIVE TREATMENT ON STROKE

Abstract Background and aims Hypertension is a major risk factor for stroke. Observational studies suggest frailty modifies the impact of hypertension; thus, frail individuals may require different treatment approaches for stroke risk reduction than non-frail individuals. Methods A single-stage individual participant data (IPD) meta-analysis using data from four landmark randomized, double-blind, placebo-controlled antihypertensive trials. Baseline frailty in each trial was assessed using the Frailty Index (FI) as a continuous and binary (FI ≤ 0.21 vs > 0.21) variable. Effects of antihypertensive treatment on outcomes by FI were examined using Fine-Gray models (adjusted for age, sex, education) yielding subdistribution hazard ratios (sHRs) for non-fatal stroke, accounting for the competing risk of mortality, and Cox regression yielding hazard ratios for major cerebrovascular events. Results A total of 24122 participants (mean age 68.5 years; 44% female) were included, with a median follow-up of 4.3 years. The median (interquartile interval) FI was 0.16(0.11–0.23) and 29% had FI > 0.21. The protective effect of antihypertensive treatment on non-fatal stroke was stronger in participants with FI ≤ 0.21 (sHR 0.72, 95% CI:0.63-0.82), than FI > 0.21 (sHR 1.00, 95% CI:0.82–1.23) (interaction P = 0.008, Figure 1). Significant interactions were also observed for major cerebrovascular event (P = 0.015). Conclusions This original IPD meta-analysis examined frailty as a modifier of antihypertensive treatment efficacy and found treatment was less protective against stroke in participants with higher frailty levels. This finding underscoring the importance of incorporating frailty assessments into treatment decisions when initiating antihypertensive treatment to prevent stroke in hypertensive patients. Conflict of interest Linan Chen: nothing to disclose; Katie Harris: nothing to disclose; Xiaoying Chen: nothing to disclose; Craig Anderson: nothing to disclose; John Chalmers: nothing to disclose; Kenneth Rockwood: nothing to disclose; David Ward: nothing to disclose; Ruth Hubbard: nothing to disclose; Ruirui Wang: nothing to disclose; Christine Jenkins: nothing to disclose; Jeff Williamson: nothing to disclose; Mark Woodward: nothing to disclose; Ruth Peters: nothing to disclose. Figure 1 - belongs to Results