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Lookup NU author(s): Dr Francesca Rubino, Helen MossopORCiD, Dr Darragh Twomey, Dr David AustinORCiD, Dr Murugu Veerasamy, Professor Vijay KunadianORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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.
Author(s): Rubino F, Mossop H, Ripley DP, Carter J, Twomey D, Cooke J, Austin D, Veerasamy M, Kelly D, Felmeden D, Anand A, Newby DE, Storey RF, Fox KAA, Pocock SJ, Kunadian V
Publication type: Article
Publication status: Published
Journal: JAMA Network Open
Year: 2026
Volume: 9
Issue: 4
Online publication date: 21/04/2026
Acceptance date: 26/01/2026
Date deposited: 06/05/2026
ISSN (electronic): 2574-3805
Publisher: American Medical Association
URL: https://doi.org/10.1001/jamanetworkopen.2026.7316
DOI: 10.1001/jamanetworkopen.2026.7316
Data Access Statement: Additional Information: ISRCTN 11343602 Data available: No Additional Information Explanation for why data not available: Long term follow-up still ongoing.
PubMed id: 42012832
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