Comment

www.thelancet.com Vol 387 March 12, 2016 1029

Management of acute coronary syndrome in the very elderlyThe very elderly, those aged 80 years or older, constitute a rapidly increasing subgroup of patients presenting with ischaemic heart disease.1 Non-ST-elevation (NSTE)-acute coronary syndrome is the most common manifestation of acute ischaemic heart disease in the very elderly, with advanced age conferring higher risks of mortality, recurrent ischaemia, and readmission to hospital.1–3 Present guidelines recommend a routine invasive strategy for the management of NSTE-acute coronary syndrome in patients at high risk of recurrent events.4 These recommendations do not distinguish older from younger patients, despite the scarcity of evidence from randomised controlled trials for patients aged 80 years or older.4

Management of NSTE-acute coronary syndrome has many challenges in very elderly patients, who often present later, have atypical symptoms, and are a more heterogeneous cohort than younger patients. These patients are also more likely to have comorbidities, cognitive decline, physical frailty, polypharmacy, and more complex coronary artery disease with greater ischaemic burden.1 These factors could be perceived to diminish the benefi ts and increase the risk of complications from invasive treatment. Consequently the management of very elderly patients has traditionally been more conservative than guidelines recommend, with suboptimum access to early angiography and optimum revascularisation and medical treatment.5

This underservicing poses a risk–treatment paradox. Evidence from registries of octogenarians6,7 and further analysis of trials with under-representation of patients older than 65 years3,8,9 suggest that the very elderly might derive greater benefi t from a routine invasive strategy than younger patients. The only randomised controlled trial previously dedicated to comparing routine versus selective invasive management of NSTE-acute coronary syndrome in very elderly patients was underpowered and did not lend support to an overall benefi t, although fewer clinical events were recorded in participants with baseline troponin elevation.10

In The Lancet, Nicolai Tegn and colleagues11 report the results of the open-label After Eighty study, which compared early invasive and conservative approaches to management of NSTE-myocardial infarction (NSTEMI) and unstable angina pectoris in patients aged 80 years

or older. The fi ndings impressively support the invasive strategy, with the mean time to coronary angiography being 3 days after presentation. The primary composite outcome of myocardial infarction, need for urgent revascularisation, stroke, and death, was substantially lower in the invasive group at median follow-up of 1·53 years (occurring in 93 [40·6%] of 229 patients vs 140 [61·4%] of 228 patients; hazard ratio [HR] 0·53, 95% CI 0·41–0·69; number needed to treat 4·8, 3·4–8·5). This outcome was driven by reductions in myocardial infarction (HR 0·52, 0·35–0·76) and urgent revascularisation (0·19, 0·07–0·52). The absence of mortality benefi t in the invasive group, consistent with previous studies, might be representative of study size or observations from other reports that most deaths after contemporary percutaneous coronary intervention have non-cardiovascular causes.12

Patients in After Eighty11 had high-risk characteristics at enrolment, including high prevalence of raised troponin and comorbid disorders, mean glomerular fi ltration rates of 52–54 mL/min, and near equal sex distribution. However, by design the participants were required to be clinically stable with no persisting ischaemia before randomisation. Although 4187 octogenarians presented with NSTEMI or unstable angina, only 457 were actually enrolled because patients were excluded because of logistical diffi culties, refusal to participate, or meeting exclusion criteria such as poor study protocol compliance, life expectancy of less

AFP

Published OnlineJanuary 12, 2016http://dx.doi.org/10.1016/S0140-6736(16)00036-2

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Comment

1030 www.thelancet.com Vol 387 March 12, 2016

than 1 year, clinical instability, and continuing or recent bleeding. These issues, resulting in a small proportion of eligible participants, emphasise the diffi culties of trials with a very elderly population, but also suggest that the results might not be applicable to most octogenarians with NSTEMI or unstable angina.

Revascularisation rates approached 50% in the invasive group and only 4% in the conservative group. The low rate of percutaneous coronary intervention in the conservative group is consistent with the need for clinical stability at time of enrolment and is much lower than in other studies.3,8,10 Use of evidence-based drugs was high in both groups and dropout rates low. These factors and predominant enrolment of troponin-positive NSTEMI would have promoted the substantial treatment benefi t in the invasive group. The clinical event rates continued to diverge until at least 1 year of follow-up, with no subgroup diff erences apart from an attenuated treatment eff ect with increasing age and no signifi cant benefi t in the small numbers of patients older than 90 years.

After Eighty11 reassures us that invasive management of NSTEMI or unstable angina can be done in clinically stable octogenarians without compromising patient safety. Contrast-induced nephropathy and major bleeding events were much less frequent in the invasive group than in previous studies. The lower frequency of these adverse events happened despite high usage of dual antiplatelet treatment, use of oral anticoagulation for concomitant atrial fi brillation, and a relatively high prevalence of renal dysfunction. The predominant use of radial artery access, the absence of glycoprotein IIb or IIIa inhibitor use, and the careful nature of the exclusion criteria would all have contributed to the acceptable bleeding rates.

The After Eighty study11 provides the most compelling evidence so far validating existing guidelines for routine invasive management of NSTEMI or unstable angina in the very elderly. Its results underline some of the strengths of contemporary best-practice management, but still remind us that decision making in elderly patients has to be individually tailored, considering life expectancy, comorbid illnesses, bleeding risk, cognitive and functional status, and patient preference. Further analysis should address the eff ect of invasive management on quality-of-life measures, readmission to hospital, and health-care

costs. However, other studies will need to address whether invasive management of NSTE-acute coronary syndrome in the very elderly should involve complete or culprit lesion-only revascularisation, and use of new antiplatelet and high-dose statins. Finally, as we redefi ne age limits for invasive management, whether this should extend to nonagenarians as well remains to be seen.

*Peter J Psaltis, Stephen J NichollsSchool of Medicine, University of Adelaide, Adelaide, SA, Australia; and Vascular Research Centre, Heart Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australiapeter.psaltis@sahmri.com

SJN has received research funding from AstraZeneca, Amgen, Cerenis, Eli Lilly, The Medicines Company, Resverlogix, Novartis, InfraReDx; personal fees from Boehringer Ingelheim, CSL Behrin, and Merck; and research funding and personal fees from Sanofi -Regeneron. PJP declares no competing interests.

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11 Tegn N, Abdelnoor M, Aaberge L, et al, for the After Eighty study investigators. Invasive versus conservative strategy in patients aged 80 years or older with non-ST-elevation myocardial infarction or unstable angina pectoris (After Eighty study): an open-label randomised controlled trial. Lancet 2016; published online Jan 12. http://dx.doi.org/10.1016/S0140-6736(15)01166-6.

12 Spoon DB, Psaltis PJ, Singh M, et al. Trends in cause of death after percutaneous coronary intervention. Circulation 2014; 129: 1286–94.