The SENIOR-RITA data suggest medical therapy is a better option for older, severely frail NSTEMI patients, says Vinay Kunadian.

Older, frail patients presenting with NSTEMI do not appear to benefit more from invasive angiography and revascularization compared with conservative medical therapy, according to a new analysis of SENIOR-RITA.

Over a median follow-up of 4.1 years, the primary endpoint of cardiovascular mortality or nonfatal MI occurred in 37.7% of frail patients treated with the invasive strategy compared with 29.4% of those who were managed conservatively (HR 1.21; 95% CI 0.88-1.67), report Francesca Rubino, MD (Newcastle University, Newcastle upon Tyne, England), and colleagues this week in JAMA Network Open.

Procedural complications were numerically higher in frail patients than in robust patients, although the difference did not reach statistical significance.

SENIOR-RITA showed that it is possible to routinely assess frailty in an acute setting, such as NSTEMI, and the new analysis “emphasizes the fact that we do need to individualize care taking on board the frailty status of patients,” senior investigator Vijay Kunadian, MD (Newcastle University), told TCTMD. “Patients who are severely frail can be treated with medical therapy alone.”

Kunadian noted that roughly one-third of NSTEMI patients were frail in SENIOR-RITA, with an equal split between men and women. While the study overall found no difference in the composite endpoint over more than 4 years of follow-up, “what is interesting is that among patients who had the highest levels of frailty, there was a signal for harm with a routine invasive strategy,” she said.

Abdulla A. Damluji, MD, PhD (Cleveland Clinic, OH), applauded the investigators for the original study, noting that it was a very difficult clinical trial to complete. However, he said, the new analysis is challenging to interpret given some of the limitations of the overall trial, including the high rate of crossover in the conservative-strategy arm, which disadvantaged the invasive approach, and the prolonged time from admission to invasive management (median time 5 days).

“I still think we have a lot of questions,” Damluji told TCTMD. “We are limited by this analysis. SENIOR-RITA is the largest clinical trial in older adults with non-ST-elevation myocardial infarction where they systematically collected frailty and multimorbidity [data]. . . . We really do need more trials in frail patients otherwise we’ll not have generalized evidence in the field.”

Nonetheless, he stressed, an invasive approach isn’t right for all frail patients. “I certainly agree with that,” said Damluji, lead author of a recent statement on managing ACS in older patients. “If someone is 95 years old and wheelchair bound, has three-vessel disease and mild forms of cognitive impairment, medical therapy is not a bad idea.”

The difficulty, he added, is that many fall into a gray zone where they’re neither robust nor frail.  

Patients Typically Excluded From RCTs

The SENIOR-RITA trial, which was conducted at 48 sites in the United Kingdom and published in the New England Journal of Medicine in 2024, was unique in that researchers included patients who typically don’t get enrolled into clinical trials given their age, frailty status, and comorbidities. In all, 1,518 patients (mean age 82 years; 45% women) were randomized to the invasive strategy of coronary angiography followed by revascularization, if necessary, or to medical therapy with aspirin plus a P2Y12 receptor antagonist, statin, beta-blocker, and ACE inhibitor or ARB.

The trial found no significant difference in the risk of cardiovascular mortality or nonfatal MI, but there was evidence of benefit with regard to nonfatal MI and repeat revascularization.

The new analysis focuses on 1,446 patients with a complete frailty assessment at baseline. Using the Fried criteria, 469 patients were classified as frail, 674 as prefrail, and 303 as robust. Frail patients were older and had a higher GRACE risk score, a greater burden of comorbidities, and a lower cognitive assessment score than the prefrail and robust patients. Among the 231 frail older patients randomized to the invasive strategy, 83.1% underwent coronary angiography.

Patients who are severely frail can be treated with medical therapy alone. Vijay Kunadian

Frail patients saw no benefit with the invasive strategy regarding the study’s primary endpoint. Numerically, deaths from cardiovascular causes were higher with the invasive strategy (25.5% vs 18.5% with the conservative approach; P = 0.07), and there was no difference in the risk of recurrent MI (14.7% vs 13.9%; P > 0.99). The risks of recurrent coronary angiography and revascularization among frail patients managed invasively were also reduced.

The primary outcome did not differ between the invasive and conservative strategy in prefrail and robust patients, but the risk of recurrent coronary angiography and revascularization was significantly reduced in both groups.

When frailty was assessed as a continuous variable, there was a significant interaction for the study’s primary endpoint (P = 0.04), which the investigators say suggests that clinical outcomes may differ by frailty status. Procedural complications occurred in 8.3% of frail patients, 3.9% of prefrail patients, and 3.4% of the robust group. Rates of the various complications were low among all three groups, except for type 2 bleeding in frail patients (2.6%).

Kunadian noted that these data highlight that not all older adults are the same. “They are very heterogeneous due to conditions such as frailty, comorbidity, cognitive impairment affecting their outcomes after NSTEMI,” she said.

In Line With Other Data

Observational studies have consistently shown that frail patients have higher risks of complications with an invasive approach, including more bleeding and vascular injury. These studies have also suggested such patients benefit from revascularization, although those data are limited by selection bias despite adjusting for confounding variables.

Damluji’s center has developed a geriatric cardiology service for managing older patients, a group that is growing in number as the population ages.

“For patients that are the highest risk, we have the geriatrician see them ahead of time and we have a standardized way of measuring age-associated risks, which we call geriatric syndromes,” he said. “These are conditions that don’t fall into one disease category, like frailty, multimorbidity, physical decline, and delirium. We have a standard way to approach these patients who are undergoing a high-risk procedure.”

With that information available, the clinician is able to best make a judgement about whether they’d benefit from a procedure, such as coronary revascularization, said Damluji. While SENIOR-RITA assessed frailty using the Fried criteria, he added, others using different metrics, which makes comparing frail patients from one trial to another difficult.

If someone is 95 years old and wheelchair bound . . . medical therapy is not a bad idea. Abdulla Damluji

In an editorial, José A. Barrabés, MD, PhD, Maria Vidal-Burdeus, MD, and Ignacio Ferreira-González, MD, PhD (all from Vall d’Hebron University Hospital, Barcelona, Spain), state that frailty should be identified and quantified in older NSTEMI patients because the extent of frailty likely modifies the effects of the management approach.

“Although the study may be underpowered to detect a modest benefit of the invasive strategy, the numerically worse outcomes in patients with the highest degree of frailty who were assigned to the invasive group—which is consistent with the findings in MOSCA-FRAIL—suggests that a neutral or even harmful effect of the invasive strategy among frail patients may be more likely,” they write.

MOSCA-FRAIL, a study of 167 frail, older patients with NSTEMI, showed that an invasive strategy did not lead to an increase in the number of days alive out of hospital when compared with conservative management. The study was prematurely terminated due to the COVID-19 pandemic.  

The editorialists point out there was a reduction in recurrent MI in the overall SENIOR-RITA trial, but that one was not observed in the frail patients. This is likely because the subanalysis was underpowered, they say, but it is also possible that other factors related to frailty, such as competing risks, more prolonged times to coronary angiography and revascularization, or crossover played a role.

Damluji agreed that both SENIOR-RITA and MOSCA-FRAIL were underpowered to detect differences in hard clinical endpoints, which emphasizes the need for more trials in this space.