Long-Term Follow-Up Confirms Efficacy of Invasive Strategy in Very Old Patients with Non-ST-Elevation ACS

By Jeffrey Zimmet, MD, PhD. Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center.

SYNOPSIS: In this long-term analysis of patients in the After Eighty Study, with a mean age of 85 years and non-ST-elevation acute coronary syndrome, an invasive strategy showed a reduction in a composite endpoint of major adverse cardiovascular events and was associated with a significant improvement in event-free survival compared with a conservative approach.

SOURCE: Berg ES, Tegn NK, Abdelnoor M, et al; After Eighty Study Investigators. Long-term outcomes of invasive vs conservative strategies for older patients with non-ST-segment elevation acute coronary syndromes. J Am Coll Cardiol 2023;82:2021-2030.

Current guidelines recommend an invasive management strategy for eligible patients presenting with non-ST-elevation acute coronary syndromes (NSTE-ACS). Most of the data on which these recommendations rest are based on studies of patients whose mean ages are in their early 60s. Trials enrolling more elderly patients have been difficult to perform, and several have been underpowered to be able to make solid conclusions.

The After Eighty trial was a multicenter, randomized controlled trial that enrolled 457 patients at least 80 years of age, presenting to 16 non-percutaneous coronary intervention-capable hospitals in Norway with NSTE-ACS. Patients randomized to an invasive strategy were transferred for coronary angiography the following day at Oslo University Hospital, while those assigned to a conservative strategy remained at the community hospital and were treated medically. Patients had to be clinically stable to be enrolled, which meant excluding those with cardiogenic shock and bleeding, but also those with ongoing or recurrent chest pain. Subjects had to have an estimated life expectancy of at least 12 months, and patients with significant dementia or other comorbidities that would be expected to affect medication adherence also were excluded.

During the four-year inclusion period, more than 4,000 patients ≥ age 80 years were admitted to the participating hospitals with NSTE-ACS. Of these, 47% met the criteria for inclusion, and ultimately just 23% were enrolled. The mean age was 85 years, and just less than half were women. Among the 228 patients in the conservative group, 10 developed new myocardial infarction (MI) or refractory angina during the index hospitalization.

At a median follow-up of 5.3 years, the primary outcome — a composite of death, MI, urgent revascularization, and stroke — was significantly less frequent among patients in the invasive group, with an incident rate ratio of 0.76 (95% confidence interval [CI], 0.63-0.93; P = 0.0057). Among the components of the primary endpoint, only MI (incidence rate ratio, 0.64; 95% CI, 0.47-0.88) and need for urgent revascularization (incidence rate ratio, 0.39; 95% CI, 0.25-0.62) were significantly different between groups. All-cause mortality and cardiovascular mortality were not significantly affected by an invasive approach. In total, the invasive strategy conferred a gain in event-free survival of 276 days at five years (95% CI, 151-400 days), with even greater gains seen in higher-risk subgroups. Although nearly half of the study patients were women, female patients in the invasive group had a higher incidence of non-obstructive coronary disease compared with men (32% vs. 14%, P = 0.001). The authors concluded that, in elderly patients with NSTE-ACS, an invasive strategy was superior to a conservative one and was associated with an improvement in event-free survival out to five years.

COMMENTARY

This trial represents an important achievement addressing treatment strategies in patients of advanced age, which is a large and growing population that is seen daily in clinical practice. Overall, the message from this study seems to be that, in appropriately selected subjects, managing elderly patients presenting with non-ST-elevation myocardial infarction with upfront cardiac catheterization is appropriate and can have clear benefits.

However, we should use caution in interpreting this trial, in particular regarding applying these results to many or even most patients in this age group. Review of the basic data shows that less than 25% of potentially eligible patients actually were enrolled. The relatively short length of stay among study patients implies that sicker or more frail subjects likely were not included.

We would all do well to recognize that mortality was not significantly affected by adoption of an invasive approach, and this should figure into informed consent discussions with all patients. As always, decisions regarding treatment approaches in NSTE-ACS in elderly patients must be tailored to the individual and assess the patient-specific risks and benefits in relation to the patient’s preferences before proceeding. For stable patients with significant estimated life expectancy, this trial reinforces an invasive approach as a valid option.