Frailty Burden and Efficacy of Initial Invasive Strategy in Chronic Coronary Disease: The ISCHEMIA Trials

Background: Frailty is common among patients with chronic coronary disease and is associated with worse outcomes. Methods: A pooled, post hoc analysis of the ISCHEMIA and ISCHEMIA-CKD trials was conducted. Baseline frailty was assessed using a Frailty Index (FI), and participants were categorized into data-derived tertiles. Multivariable Cox models with multiplicative interaction terms (frailty × treatment arm) were constructed to evaluate whether baseline frailty status modified the treatment effect of the initial invasive (vs conservative) strategy on a composite outcome of cardiovascular death, myocardial infarction, hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest and the secondary outcome of HRQoL (Seattle Angina Questionnaire [SAQ]). Results: Among 5322 participants (mean 64 years, 24% female), a high frailty burden (tertile 3 vs. tertile 1) was associated with lower baseline SAQ scores and increased risk of adverse clinical outcomes on follow-up. Baseline frailty burden did not significantly modify the effect of the initial invasive strategy on the primary composite outcome (P_interactionfrailty × intervention arm = 0.30). However, frailty significantly modified the effect of the initial invasive strategy on HRQoL, with higher baseline frailty burden associated with greater improvement in SAQ scores at 1 year with initial invasive (vs. conservative) treatment (P_interactionfrailty × intervention arm < 0.001). The treatment effect of an initial invasive vs. conservative strategy on 12-month SAQ score change was most pronounced in individuals with lower baseline SAQ scores in both higher and lower frailty burden groups. Conclusion: Patients with chronic coronary disease with a higher frailty burden are more likely to experience greater improvements in HRQoL with initial invasive management without a higher risk of adverse clinical events. Lower baseline SAQ scores predicted greater improvement in HRQoL with initial invasive management, independent of frailty burden.