A meta-analysis of randomised trials comparing a strategy of revascularisation plus medical therapy versus medical therapy alone in patients with chronic coronary syndromes, found that an invasive strategy reduced the risk of cardiac death by up to one-fifth among these patients.
Findings of the analysis were presented by Eliano Navarese (Nicolaus Copernicus University, Toruń, Poland) at EuroPCR 2021 (18–20 May, virtual) and simultaneously published in the European Heart Journal and showed a consistent reduction of cardiac mortality in favour of elective coronary revascularisation.
Through their analysis, Navarese and colleagues pooled the entire body of randomised trial evidence, as recommended by Cochrane guidelines, including a total of 19,806 patients with chronic coronary syndromes undergoing elective revascularisation from 25 randomised trials sourced through MEDLINE, EMBASE, Google Scholar and other databases. Of these patients 10,023 were randomised to revascularisation plus medical therapy and 9,783 to medical therapy alone
Outcomes were extracted at the longest available follow-up. The primary endpoint was cardiac death and secondary endpoints were all-cause death, spontaneous myocardial infarction, any myocardial infarction and stroke.
The authors reported a statistically-significant 21% relative risk reduction in cardiac death with revascularisation plus medical therapy (risk ratio 0.79, 95% confidence interval 0.67‒0.93, p<0.01), with no significant heterogeneity across trials. This result was consistent in sensitivity analyses restricted to trials that did not include patients with prior acute coronary syndromes, chronic total occlusions or prevalent use of coronary artery bypass grafting (CABG) in the invasive arm.
A trial sequential analysis showed that the addition of new trials to current evidence would be unlikely to modify the benefit of revascularisation plus medical therapy on cardiac death. For each four-year increase in the length of follow-up in the available studies, the risk of cardiac death was reduced by 19%. No significant association was found between cardiac death and medical therapy or study year.
There was a parallel significant reduction in spontaneous myocardial infarction with revascularisation plus medical therapy (risk ratio 0.74, 95% confidence interval 0.64‒0.86, p<0.01), with mild heterogeneity across trials. A meta-regression showed a significant association between the reduction in cardiac death and the reduction in spontaneous myocardial infarction. No difference was noted in all the other secondary outcomes, including all-cause death.
Speaking to Cardiovascular News, Navarese pointed out that it has been argued that older trials might have indirectly favoured revascularisation because of suboptimal medical therapy. However, he claimed that this belief is confuted by this analysis. “In each trial both treatment arms received medical therapy which was generally comparable, preserving the capacity to assess the role of revascularisation on top of standard medical treatment. Trial chronological order did not impact cardiac mortality findings. As clearly shown in the present study, the percentage use of any of the more frequently employed drug types, such as statins, antithrombotic agents, beta-blockers or ACE inhibitors/ARBs, and study year did not influence the cardiac mortality findings,” he said.
Overall, the meta-analysis indicates that the benefits of revascularisation and optimised medical therapy are additive and their combination is required to achieve maximal and durable prevention of adverse events.
The significance of the findings were highlighted in a statement by the Society for Cardiovascular Angiography & Interventions (SCAI), issued shortly after the presentation of the analysis at EuroPCR. In the statement SCAI said that the meta-analysis indicates that coronary revascularisation with PCI or CABG provides a long-term cardiovascular survival advantage over an initial conservative approach in patients with stable ischaemic heart disease by lowering rates of spontaneous MI, describing this as “a new and exciting finding related to coronary revascularisation, including PCI”.
“This comprehensive analysis clearly defines a risk-reduction in cardiovascular mortality following coronary revascularsation in patients with stable coronary artery disease that is directly related to both duration of follow-up and magnitude of risk reduction in spontaneous myocardial infarction. This mechanistically plausible benefit of revascularisation is evident through multiple sensitivity analyses,” said Dean Kereiakes, medical director of the Christ Hospital Research Institute in Cincinnati, USA, and a co-author of the study.
A further important observation highlighted by SCAI was the association of longer follow-up with increased observed benefit with an invasive strategy, and that differences in conclusions between randomised trials could be explained largely by differences in follow-up duration.
Alexandra Lansky director of the Heart and Vascular Clinical Research Program and the Cardiovascular Research Center at Yale University School of Medicine, New Haven, USA and a co-author of the study, said: “For our patients with stable coronary artery disease on medical therapy, this means that one in five will realise a survival benefit about 5.5 years after revascularisation and one in four will avoid a spontaneous heart attack. The two are related, and the survival benefit of revascularisation increases with time. For our studies, this means we need long-term follow-up focused on cardiac death to see the benefit of revascularisation.”