JAMA Intern Med 2023;183:407-415
Background: As we have previously discussed, trials comparing invasive versus conservative management in patients with non-ST elevation myocardial infarction (NSTEMI) have yielded mixed results. The average age of participants in these studies was in the 60s, and multiple comorbidities were relatively uncommon. However, many NSTEMI patients seen in clinical practice are older and have multiple comorbidities. These patients have worse prognosis and have competing risks for mortality. Whether an invasive strategy provides a benefit for this population remains uncertain.
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The MOSCA-FRAIL trial sought to compare invasive vs conservative strategy in older adults with frailty and NSTEMI.
Patients: Eligible patients had to have NSTEMI, be 70 years or older, and have frailty defined by 4 points or greater on the Clinical Frailty Scale.
Patients were excluded if they were known to have nonrevascularizable coronary artery disease, significant concomitant non-ischemic heart disease, or life expectancy less than 12 months.
Baseline characteristics: The trial randomized 167 patients from 13 hospitals in Spain – 84 randomized to invasive strategy and 83 to conservative strategy.
The average age of patients was 86 years and 47% were men. Approximately 92% had hypertension, 56% had diabetes, 77% had hyperlipidemia, 31% had prior myocardial infarction, 27% had history of atrial fibrillation, 18% had prior stroke, 44% had chronic kidney disease, and 3% were current smokers.
Procedures: Patients were randomly assigned in a 1:1 ratio to undergo invasive or conservative strategy.
In the invasive strategy, patients underwent coronary angiogram within 72 hours of admission, and revascularization was performed as appropriate. In the conservative arm, patients were treated with medical therapy alone. A coronary angiogram was permitted for recurrent ischemia during the index admission.
Medical treatment was given according to the guidelines at the time. In both arms, dual antiplatelet was recommended for one year. In patients with high bleeding risk or taking an oral anticoagulant, one antiplatelet could be stopped after the first month.
Endpoints: The primary end point was the number of days alive and out of the hospital between discharge from the index hospitalization to 1 year. The coprimary end point was the composite of cardiac death, reinfarction, or post-discharge revascularization.
Analysis was performed based on the intention-to-treat principle. The estimated sample size to provide 80% power at 5% alpha was 176 patients. This assumed that the number of days for the primary outcome in the conservative arm was 273 days and that an invasive strategy would increase that by 20%, that is 55 days.
Results: Due to the COVID pandemic, the trial was terminated early after randomizing 95% of the planned sample size. During the index admission, 98% of the patients in the invasive arm underwent coronary angiogram and 60% underwent revascularization. Among patients in the conservative arm, 9.6% underwent revascularization due to recurrent ischemia during the index admission.
The primary outcome (number of days alive and out of the hospital between discharge from the index hospitalization to 1 year) was numerically lower with the invasive arm but this was not statistically significant (mean difference 28 days, 95% CI: -7 – 62; p= 0.12).
There was no difference in the coprimary end point - cardiac death, reinfarction, or post-discharge revascularization – absolute values were not provided. The invasive strategy was associated with significantly more bleeding events requiring hospitalization (8 patients vs 1 patient, incidence rate ratio: 14.9, 95% CI: 1.7 – 129.0; p= 0.02) including 4 deaths related to bleeding.
Conclusion: In older, frail patients with NSTEMI, an invasive strategy did not significantly reduce the number of days of being alive and out of the hospital at 1-year. It also did not reduce the coprimary end point which was the composite of cardiac death, reinfarction, or post-discharge revascularization. An invasive strategy was associated with more bleeding requiring hospitalization.
The trial is small, and its results should be interpreted with caution. Nonetheless, it is an important study that paves the way for future, larger trials in this population. The primary endpoint is both meaningful and relevant to this population. The average age of participants in this trial is approximately 20 years older than those in TACTICS-TIMI 18, RITA 3, and ICTUS. It is important to recognize that older, frail patients with multiple comorbidities are significantly underrepresented in clinical trials and likely derive less benefit or even harm from interventions.
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