Effect of Routine Invasive vs Conservative Strategy in Older Adults With Frailty and Non–ST-Segment Elevation Acute Myocardial Infarction

Abstract

ImportanceTo our knowledge, no randomized clinical trial has compared the invasive and conservative strategies in frail, older patients with non–ST-segment elevation acute myocardial infarction (NSTEMI).ObjectiveTo compare outcomes of invasive and conservative strategies in frail, older patients with NSTEMI at 1 year.Design, Setting, and ParticipantsThis multicenter randomized clinical trial was conducted at 13 Spanish hospitals between July 7, 2017, and January 9, 2021, and included 167 older adult (≥70 years) patients with frailty (Clinical Frailty Scale score ≥4) and NSTEMI. Data analysis was performed from April 2022 to June 2022.InterventionsPatients were randomized to routine invasive (coronary angiography and revascularization if feasible; n = 84) or conservative (medical treatment with coronary angiography for recurrent ischemia; n = 83) strategy.Main Outcomes and MeasuresThe primary end point was the number of days alive and out of the hospital (DAOH) from discharge to 1 year. The coprimary end point was the composite of cardiac death, reinfarction, or postdischarge revascularization.ResultsThe study was prematurely stopped due to the COVID-19 pandemic when 95% of the calculated sample size had been enrolled. Among the 167 patients included, the mean (SD) age was 86 (5) years, and mean (SD) Clinical Frailty Scale score was 5 (1). While not statistically different, DAOH were about 1 month (28 days; 95% CI, −7 to 62) greater for patients managed conservatively (312 days; 95% CI, 289 to 335) vs patients managed invasively (284 days; 95% CI, 255 to 311; P = .12). A sensitivity analysis stratified by sex did not show differences. In addition, we found no differences in all-cause mortality (hazard ratio, 1.45; 95% CI, 0.74-2.85; P = .28). There was a 28-day shorter survival in the invasive vs conservatively managed group (95% CI, −63 to 7 days; restricted mean survival time analysis). Noncardiac reasons accounted for 56% of the readmissions. There were no differences in the number of readmissions or days spent in the hospital after discharge between groups. Neither were there differences in the coprimary end point of ischemic cardiac events (subdistribution hazard ratio, 0.92; 95% CI, 0.54-1.57; P = .78).Conclusions and RelevanceIn this randomized clinical trial of NSTEMI in frail older patients, there was no benefit to a routine invasive strategy in DAOH during the first year. Based on these findings, a policy of medical management and watchful observation is recommended for older patients with frailty and NSTEMI.Trial RegistrationClinicalTrials.gov Identifier: NCT03208153

Importance of Designing Trials for Older Adults With Complex Medical Conditions

“…Thus, the randomized clinical trial in this issue of JAMA Internal Medicine by Sanchis et al 1 is an important and innovative addition to address this important clinical question. They randomized older adult patients (≥70 years) with frailty, defined by a Clinical Frailty Scale (CFS) score of 4 or higher, and NSTEMI to a routine invasive strategy (n = 84) or conservative strategy (n = 83).…”

“…Patients who are older and frailer are at higher risk of experiencing competing events and treatment-related harm, such as noncardiovascular death and complications of invasive procedures, which may negate or reverse benefits reported in trials enrolling patients with less complex medical conditions. For these reasons, designing trials specifically for older adults with frailty and multimorbidity, such as the one by Sanchis et al, 1 are essential for informing best practices.…”

“…As proof, the average trial participant had 2 or more major comorbidities. 1 The second novel design feature is the primary end point of DAOH. Conventional composite end points used in cardiovascular trials, which tend to include cause-specific mortality along with nonfatal events like MI, have recognized limitations and are less likely to be meaningful for geriatric patients with frailty who are at high risk for hospitalization and death from cardiac and noncardiac causes.…”

“…This trial included patients 70 years or older with a CFS score of 4 or above, which is defined as “apparently vulnerable—although not frankly dependent, these people commonly complain of being ‘slowed up’ or have disease symptoms.” These inclusion criteria ensured a unique population of patients (mean age, 86 years; and mean CFS score, 5.1) that clinicians can relate to in their daily practice (ie, a patient in their 70s or 80s with mild frailty defined by limited dependence on others for instrumental activities of living). The use of the CFS allowed the authors to avoid concerns related to underrepresentation of patients with comorbidity, cognitive impairment, and disability, as all these items are captured in the scale.…”

“…Using this assumption, they tested the hypothesis that an invasive strategy would increase DAOH by 20%, representing a 55-day increase for the invasive strategy (invasive strategy assumption = 328 DAOH vs conservative strategy assumption = 273 DAOH). A sample size of 176 patients (88 per arm) yielded an estimated power of 80%, 2-sided α level of .05, allowing for a 10% loss to follow-up …”