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With improving life expectancy in developed countries, the proportion of people aged >65 years will significantly increase over the next 20 years, and the prevalence of those >85 years of age will almost double. Importantly, increasing age is among the major predictors of adverse events in patients with coronary artery disease (CAD), with elderly patients showing higher in-hospital mortality and periprocedural complication rates as compared with younger individuals. However, elderly patients are less likely to receive evidence-based therapies for CAD, particularly referral to cardiac catheterization and coronary revascularisation. In the setting of acute coronary syndromes (ACS) the expected benefit from an early invasive approach has been demonstrated to be similar across different age categories; however, elderly patients are still frequently managed conservatively because of a systematic overestimation of periprocedural complications and underestimation of the risk of spontaneous adverse events. These conditions are particularly evident in the setting of non-ST-segment elevation ACS (NSTEACS), which represent the most frequent type of ACS among elderly patients, frequently characterised by atypical symptoms, challenging comorbidities (ie, atrial fibrillation, pulmonary disease, peripheral vascular disease), and extensive CAD burden.
Despite registries confirming the high prevalence of NSTEACS among elderly patients, this patient subset is typically under-represented in randomised controlled trials (RCTs) that generally favour the inclusion of younger and relatively less comorbid patients. Accordingly, despite current NSTEACS guidelines recommending a routine invasive approach for the majority of patients irrespective of age, the opportunity of early coronary angiography and revascularisation in the elderly is still disputed, due to scarce and inconclusive evidence. In this context, only a handful of relatively small RCTs specifically compared an early invasive strategy versus an initially conservative approach in elderly patients with NSTEACS. In particular, the Italian Elderly ACS study was the first trial to suggest that an early aggressive strategy based on systematic coronary angiography and revascularisation when indicated could be superior to an initially conservative strategy in elderly individuals with NSTEACS and elevated cardiac troponin, while no difference was revealed in patients with normal cardiac biomarkers.1 Thereafter, the After Eighty Study confirmed that an invasive strategy with early coronary revascularisation (performed in 50% of the patients) is also beneficial in very old patients (mean age ~84 years) with NSTEACS and raised troponin, yielding a lower incidence of myocardial infarction (MI) at short-term follow-up, despite a similar in-hospital complication rate.2 However, this limited evidence in favour of an early invasive strategy needs to be corroborated by an adequately powered RCT, which has not been performed so far, nor is currently underway, leaving the controversy on the management of this key patient population still open.
In their Heart manuscript, Gnanenthiran et al report the results of a meta-analysis of the available evidence comparing an early invasive approach versus an initially conservative strategy in elderly patients with NSTEACS.3 In particular, the authors collected information from six RCTs and three registries, for a total of about 20 000 patients >75 years old (1887 enrolled in RCTs), treated between 1996 and 2014 (table 1).1 2 4–8 Overall patient characteristics well represent a contemporary population of elderly patients admitted for NSTEACS, with a mean age of 84 years and a high prevalence of comorbidities (ie, 31% diabetic, 24% previous MI, 12% chronic kidney disease). The main findings of the study are that a routine invasive therapy was associated with a significantly lower in-hospital mortality (OR 0.65, 95% CI 0.53 to 0.79; p<0.0001) and MI rate (OR 0.43, 95% CI 0.30 to 0.61; p<0.00001), as well as lower mortality at follow-up (range 6 months to 5 years) (OR 0.67, 95% CI 0.61 to 0.74; p<0.00001) and MI rate at follow-up (OR 0.56, 95% CI 0.45 to 0.70; p<0.00001). Additionally, a routine invasive strategy also lowered the revascularisation rate at 12–18 months (OR 0.27, 95% CI 0.13 to 0.56; p=0.0005) and stroke rate (OR 0.53, 95% CI 0.30 to 0.95; p=0.03). Importantly, the inter-study heterogeneity was very low, particularly for events at follow-up, giving consistency to the results. Furthermore, very similar results were obtained in the sensitivity analyses restricted to RCTs or to the most recent studies, performed in the drug-eluting stent era.1 2 4 The authors also performed an interesting meta-regression analysis describing a trend towards a reduced benefit of an early invasive approach with increasing age, possibly suggesting the existence of an upper age limit for the expected benefit of revascularisation in elderly patients with NSTEACS.
As expected, the prognostic benefit of an early invasive approach was gained at the expense of a significantly higher incidence of major bleeding, both in-hospital (OR 2.37, CI 1.53 to 3.68; p=0.0001) and at follow-up (OR 2.38, CI 1.64 to 3.45, p<0.00001). However, the difference between routine invasive and initially medically managed groups was almost nil in studies published in the last 5 years, probably reflecting a higher rate of radial artery access for coronary interventions and a lower use of glycoprotein IIb/IIIa inhibitors (table 1).
The authors offer additional evidence on the management of an important and growing population suffering from NSTEACS, that have been rather neglected in clinical trials. Pooling together relatively homogeneous studies, they were able to demonstrate that elderly patients obtain a net prognostic improvement with a routine invasive approach, similarly to younger individuals, indicating that the management of octogenarians with NSTEACS should not be routinely conservative. However, a number of limitations should also be acknowledged. First of all, meta-analyses are not the primary source of scientific evidence, particularly when not derived from individual patient data. Second, the evidence in favour of an early invasive strategy comes mostly from a large Polish registry rather than from RCTs. On the other hand, the increased risk of major bleeding associated with an early invasive approach is mainly derived from the Polish registry, in contrast to the three smaller RCTs. A further limitation of the study is the lack of insights into what factors underlie the steep decline in bleeding complications in the early invasive arm reported in the most recent studies. The wide range of enrolment years among the studies selected for the meta-analysis also represents a limitation in terms of homogeneity of drug treatment (particularly regarding antiplatelet therapy) and of revascularisation modalities (use of bare metal stents vs drug-eluting stents). Finally, as the vast majority of patients included in the meta-analysis showed elevated troponin on admission (table 1), the results of the meta-analysis cannot be applied to elderly patients with NSTEACS without elevated troponin, who constitute a lower-risk population that might not benefit from a routine invasive approach.
While adequately-powered RCTs are still needed to define the most appropriate approach in elderly patients with NSTEACS, the meta-analysis by Gnanenthiran et al provides new, good-quality evidence supporting an early invasive strategy, which was associated with a significant reduction in most clinical hard endpoints. In this context, strategies able to limit the occurrence of bleeding complications (ie, trans-radial approach) and to better guide revascularisation (ie, invasive assessment of coronary flow reserve in the case of multivessel disease) should be implemented to maximise the clinical benefit and contain the risks of a routine invasive approach. Finally, the issue of how to treat nonagenarians remains open; although some evidence suggests a progressive decrease of benefit from a routine invasive approach beyond 85 years of age, we should still decide case-by-case whether an early coronary angiography is warranted.
Contributors Both authors contributed to the drafting of the manuscript.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.
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