Invasive vs Conservative Strategy for Frail Older Patients With Myocardial Infarction

Importance: Frail older patients with non-ST-elevation myocardial infarction (NSTEMI) experience an increased risk of major adverse cardiovascular events. The beneficial role of an invasive strategy over a conservative strategy among frail patients with NSTEMI is unclear. Objective: To compare the clinical outcomes of an invasive strategy with those of a conservative strategy among older patients with NSTEMI stratified by frailty status. Design, Setting, and Participants: In this prespecified exploratory subgroup analysis from the SENIOR-RITA randomized clinical trial, patients were screened across 48 National Health Service trusts in England and Scotland from November 1, 2016, through March 31, 2023. The SENIOR-RITA trial included patients with NSTEMI aged 75 years or older, randomized to an invasive strategy with coronary angiography, revascularization if needed, and optimal medical therapy vs a conservative strategy with optimal medical therapy only. In this analysis, frailty status was defined using the Fried frailty criteria (frail, ≥3 criteria present). Statistical analysis was performed from March through November 2025. Interventions: Invasive vs conservative strategy. Main Outcomes and Measures: The primary composite outcome was the time to cardiovascular death or nonfatal myocardial infarction. All participants were analyzed according to the intention-to-treat principle. Results: Fried frailty criteria were available for 1446 of the 1518 randomized patients (95.3%), of whom 469 (32.4%; median age, 83 years [IQR, 80-86 years]; 240 women [51.2%]) met criteria for frailty. The primary outcome among frail patients occurred among 87 of 231 patients (37.7%) in the invasive group and 70 of 238 patients (29.4%) in the conservative group (hazard ratio [HR], 1.21; 95% CI, 0.88-1.67) over a median follow-up of 4.1 years (IQR, 2.8-4.6 years). When frailty was analyzed as a continuous variable, there was a significant interaction with treatment such that patients at the highest levels of frailty had a potential signal for harm with routine invasive strategy. There were no significant treatment differences across frailty categories for cardiovascular death (HR, 1.44; 95% CI, 0.97-2.10) or nonfatal myocardial infarction (HR, 1.00; 95% CI, 0.61-1.63). Conclusions and Relevance: In this subgroup analysis of a randomized clinical trial, an invasive strategy did not reduce the risk of a composite outcome of cardiovascular death or nonfatal myocardial infarction compared with a conservative strategy, with a potential signal for increased risk of harm among those at the highest levels of frailty. These findings underscore the need for individualized, frailty-informed treatment strategies. Trial Registration: isrctn.org Identifier: ISRCTN11343602.