Spain: Secondary Analysis of a Randomized Clinical Trial

A secondary analysis of a randomized clinical trial (RCT) of 167 patients with frailty and non-ST-segment elevation myocardial infarction (NSTEMI) showed an early harm followed by later benefit with an initial invasive strategy, resulting in a neutral effect on survival at 4 years.

"A routine invasive strategy did not reduce the number of days alive at a median follow-up of 1113 days versus a conservative strategy," the researchers reported in JAMA Network Open. Invasive treatment was linked with shorter survival within the first year but more prolonged survival after the first year.

The MOSCA-FRAIL RCT

The MOSCA-FRAIL RCT compared invasive and conservative treatment strategies in patients with frailty with NSTEMI. It revealed no differences in the number of days alive and out of the hospital at one year. Juan Sanchis, CIBERCV, Valencia, Spain, and colleagues sought to assess the outcomes of the MOSCA-FRAIL trial during extended follow-up.

The MOSCA-FRAIL trial was conducted at 13 hospitals in Spain between 2017 and 2021, and included 167 adults (aged ≥70 years) with frailty (Clinical Frailty Scale score ≥4) and NSTEMI. Follow-up in the preplanned secondary analysis extended to January 31, 2023.

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. Among the 167 included patients in the analysis, the mean age was 86 years; 52.7% were women.

Study Endpoints and Findings

The study's primary endpoint was the difference in restricted mean survival time (RMST). Secondary endpoints were readmissions for any cause, considering recurrent readmissions.

The researchers reported the following findings:

• A total of 93 deaths and 367 readmissions accrued.
• The RMST for all-cause death over the entire follow-up was 3.13 years in the invasive and 3.06 years in the conservative treatment groups.
• The RMST analysis showed inconclusive differences in survival time (invasive minus conservative difference, 28 days).
• Patients under invasive treatment tended to have shorter survival in the first year (−28 days), which improved after the first year (192 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).
• Early harm was more evident in the subgroup with a Clinical Frailty Scale score greater than 4.
• There were no differences for the secondary endpoints.

Conclusion

In conclusion, an invasive treatment strategy failed to improve outcomes at a median follow-up of 1113 days. However, the researchers observed a differential distribution of deaths, with early harm followed by later benefit. The phenomenon of depletion of susceptible patients may be responsible for this behavior.

"Therefore, an initial conservative strategy may be more suitable for patients with NSTEMI and high levels of frailty," the researchers wrote. "These findings provide valuable insights for clinical decision-making in this vulnerable patient population."

Reference

Sanchis J, Bueno H, García-Blas S, et al. Invasive Treatment Strategy in Adults With Frailty and Non–ST-Segment Elevation Myocardial Infarction: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024;7(3):e240809. doi:10.1001/jamanetworkopen.2024.0809