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. 2024 Mar 4;7(3):e240809.
doi: 10.1001/jamanetworkopen.2024.0809.

Invasive Treatment Strategy in Adults With Frailty and Non-ST-Segment Elevation Myocardial Infarction: A Secondary Analysis of a Randomized Clinical Trial

Juan Sanchis  1 , Héctor Bueno  2   3   4 , Sergio García-Blas  1 , Oriol Alegre  5 , David Martí  6 , Manuel Martínez-Sellés  7 , Laura Domínguez-Pérez  2   3   4 , Pablo Díez-Villanueva  8 , Jose A Barrabés  9 , Francisco Marín  10 , Adolfo Villa  11 , Marcelo Sanmartín  12 , Cinta Llibre  13 , Alessandro Sionís  14 , Antoni Carol  15 , Agustín Fernández-Cisnal  1 , Elena Calvo  5 , María José Morales  6 , Jaime Elízaga  7 , Iván Gómez  2   3   4 , Fernando Alfonso  8 , Bruno García Del Blanco  9 , Francesc Formiga  5 , Eduardo Núñez  1 , Julio Núñez  1 , Albert Ariza-Solé  5
Affiliations

Invasive Treatment Strategy in Adults With Frailty and Non-ST-Segment Elevation Myocardial Infarction: A Secondary Analysis of a Randomized Clinical Trial

Juan Sanchis et al. JAMA Netw Open. .

Abstract

Importance: The MOSCA-FRAIL randomized clinical trial compared invasive and conservative treatment strategies in patients with frailty with non-ST-segment elevation myocardial infarction (NSTEMI). It showed no differences in the number of days alive and out of the hospital at 1 year.

Objective: To assess the outcomes of the MOSCA-FRAIL trial during extended follow-up.

Design, setting, and participants: The MOSCA-FRAIL randomized clinical trial was conducted at 13 hospitals in Spain between July 7, 2017, and January 9, 2021, and included 167 adults (aged ≥70 years) with frailty (Clinical Frailty Scale score ≥4) and NSTEMI. In this preplanned secondary analysis, follow-up was extended to January 31, 2023. Data analysis was performed from April 5 to 29, 2023, using the intention-to-treat principle.

Interventions: Patients were randomized to a routine invasive (coronary angiography and revascularization if feasible [n = 84]) or a conservative (medical treatment with coronary angiography only if recurrent ischemia [n = 83]) strategy.

Main outcomes and measures: The primary end point was the difference in restricted mean survival time (RMST). Secondary end points included readmissions for any cause, considering recurrent readmissions.

Results: Among the 167 patients included in the analysis, the mean (SD) age was 86 (5) years; 79 (47.3%) were men and 88 (52.7%) were women. A total of 93 deaths and 367 readmissions accrued. The RMST for all-cause death over the entire follow-up was 3.13 (95% CI, 2.72-3.60) years in the invasive and 3.06 (95% CI, 2.84-3.32) years in the conservative treatment groups. The RMST analysis showed inconclusive differences in survival time (invasive minus conservative difference, 28 [95% CI, -188 to 230] days). Patients under invasive treatment tended to have shorter survival in the first year (-28 [95% CI, -63 to 7] days), which improved after the first year (192 [95% CI, 90-230] days). Kaplan-Meier mortality curves intersected, displaying higher mortality to 1 year in the invasive group that shifted to a late benefit (landmark analysis hazard ratio, 0.58 [95% CI, 0.33-0.99]; P = .045). Early harm was more evident in the subgroup with a Clinical Frailty Scale score greater than 4. No differences were found for the secondary end points.

Conclusions and relevance: In this extended follow-up of a randomized clinical trial of patients with frailty and NSTEMI, an invasive treatment strategy did not improve outcomes at a median follow-up of 1113 (IQR, 443-1441) days. However, a differential distribution of deaths was observed, with early harm followed by later benefit. The phenomenon of depletion of susceptible patients may be responsible for this behavior.

Trial registration: ClinicalTrials.gov Identifier: NCT03208153.

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Conflict of interest statement

Conflict of Interest Disclosures: Prof Sanchis reported receiving payments for presentations from Boston Scientific Corporation and Abbott Vascular outside the submitted work. Dr Bueno reported receiving grant funding from the European Union, Instituto de Salud Carlos III, Sociedad Española de Cardiologí, Boehringer Ingelheim, and Janssen Global Services LLC, and personal fees from AstraZeneca, Novartis AG, Novo Nordisk A/S, and Organon & Co outside the submitted work. Dr Marín reported receiving grant funding from Bayer AG, Grupo Ferrer Internacional SA, and Boehringer-Ingelheim; support for meetings from Esteve; and serving on the advisory board for the Atrial Fibrillation Network. Dr Sanmartin reported receiving conference fees from Amgen Inc, Boehringer Ingelheim, and AstraZeneca outside the submitted work. Dr J. Núñez reported receiving personal fees from Alleviant Medical Inc, AstraZeneca, Boehringer Ingelheim, Novartis AG, NovoNordisk A/S, Pfizer Inc, and Laboratorios Farmaceuticos Rovi SA outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Restricted Mean Survival Curves for All-Cause Mortality Between Conservative and Invasive Treatment Strategies
A and B, The follow-up period was initiated at randomization. C and D, The follow-up period was initiated 1 year after randomization. Shaded areas indicate the 95% CI.
Figure 2.
Figure 2.. Kaplan-Meier Curves Comparing All-Cause Mortality Between Conservative and Invasive Treatment Strategies
A, The follow-up period for the analysis was initiated at randomization. B, Thirty-eight patients were excluded due to early events. The follow-up period for the analysis was initiated 1 year after randomization.
Figure 3.
Figure 3.. Restricted Mean Survival Curves for All-Cause Mortality Between Conservative and Invasive Treatment Strategies by Clinical Frailty Subgroups
The subgroup with frailty was defined by a Clinical Frailty Scales (CFS) score of greater than 4; the vulnerable subgroup, a CFS score of 4. Shaded areas indicate the 95% CI.
Figure 4.
Figure 4.. Restricted Mean Survival Curves Between Conservative and Invasive Treatment Strategies for the Secondary End Points
The follow-up period was initiated at randomization. Cardiac events include reinfarction, revascularization, unstable angina, heart failure, or other cardiac reasons. RMST indicates restricted mean survival time. Differences in RMSTs are calculated as invasive minus conservative treatment. Shaded areas indicate the 95% CI.
See this image and copyright information in PMC

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