A routine invasive strategy did not reduce the risk of cardiovascular death or nonfatal myocardial infarction compared with conservative management among patients with frailty aged 75 years or older with non–ST-elevation myocardial infarction, with a signal for worse outcomes among those with the highest frailty levels, according to a prespecified exploratory subgroup analysis of the SENIOR-RITA randomized clinical trial.
Researchers evaluated 1,446 patients with available frailty data, including 469 patients (32%) who met Fried frailty criteria. Patients were randomized to an invasive strategy—coronary angiography with revascularization when appropriate plus optimal medical therapy—or a conservative strategy of optimal medical therapy alone. The primary end point was time to cardiovascular death or nonfatal myocardial infarction over a median follow-up of 4.1 years.
Among patients with frailty, the primary outcome occurred in 38% of those assigned to invasive care and 29% assigned to conservative care, corresponding to a hazard ratio of 1.21. Cardiovascular death occurred in 26% vs 18%, respectively (hazard ratio, 1.44), while nonfatal myocardial infarction occurred in 15% vs 14% (hazard ratio, 1.00).
"Our findings suggest that, among frail patients, an invasive approach was not associated with a statistically significant reduction in the primary composite outcome or its individual components," wrote lead researcher Francesca Rubino, MD, of the Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, and colleagues.
Notably, the invasive strategy did not reduce myocardial infarction in this subgroup, in contrast to the overall SENIOR-RITA trial population, in which invasive management was associated with a modest reduction in nonfatal myocardial infarction. This suggests that expected benefits of invasive care may not extend to patients with frailty.
When frailty was analyzed categorically, there was no statistically significant interaction between frailty group and treatment for the primary outcome (P = .07). However, when assessed as a continuous variable, frailty severity significantly modified treatment effect, with the relative disadvantage of invasive management increasing at higher frailty scores. These findings suggest a potential signal for harm among patients at the highest levels of frailty.
No statistically significant differences were observed across secondary outcomes, including all-cause mortality, hospitalization for heart failure, stroke, transient ischemic attack, or bleeding. As expected, patients initially assigned to invasive management required fewer subsequent unplanned coronary angiography and revascularization procedures during follow-up.
Among 231 patients with frailty assigned to invasive management, 192 (83%) underwent coronary angiography. The remaining patients did not undergo the procedure, most often because of clinical decisions reflecting changes in condition, highlighting the complexity of applying invasive strategies in this population and the potential for dilution of treatment effects in intention-to-treat analyses.
Procedural complications were numerically more common among patients with frailty undergoing invasive treatment, occurring in 8% of cases, although individual complications were uncommon.
The findings are consistent with prior evidence from the MOSCA-FRAIL randomized trial, which also showed no clear benefit of routine invasive management in older patients with frailty and suggested potential harm at higher levels of frailty severity. Together, these data support the concept that frailty not only identifies higher-risk patients but may also modify the balance of benefit and risk with invasive strategies.
A competing-risk analysis accounting for noncardiovascular death produced similar results, supporting the robustness of the findings in this high-risk population.
In an invited commentary, José A. Barrabés, MD, PhD, Maria Vidal-Burdeus, MD, and Ignacio Ferreira-González, MD, PhD, of Vall d'Hebron University Hospital and affiliated research networks in Barcelona, wrote that the findings underscore the importance of assessing not only the presence but also the severity of frailty when making treatment decisions for older patients with non–ST-elevation myocardial infarction.
The researchers noted several limitations, including the exploratory subgroup design, limited statistical power within the frail cohort, lack of adjustment for multiple comparisons, and potential residual imbalance because randomization was not stratified by the frailty measure used in this analysis. Patients with more advanced frailty were also less likely to be enrolled, which may limit generalizability.
The SENIOR-RITA trial was funded by the British Heart Foundation. Several study researchers reported financial relationships with industry. Commentary disclosures included nonfinancial support from Bayer for Dr Ferreira-González and research funding for Dr Barrabés from Instituto de Salud Carlos III, Spain, and CIBERCV.
Source: JAMA Network Open