The ISCHEMIA trial found no significant difference between an invasive vs. a conservative strategy in patients with chronic coronary syndromes and moderate to severe ischemia at a mean of 3.2 years. However, the cumulative difference in the estimates of cardiac death between the invasive and conservative strategies tended to increase numerically over time (e.g., 0.3% in favor of the invasive strategy at 2 years and 1.3% at 5 years). Because the ISCHEMIA trial was not powered for cardiac mortality and did not focus on long-term follow-up, the rationale for a meta-analysis emerged.
At EuroPCR 2021, Eliano Navarese of Nicolaus Copernicus University - Bydgoszcz, Poland, and colleagues present the results of a new meta-analysis of revascularization plus medical therapy versus medical therapy alone. A total of 19,806 patients with chronic coronary syndromes undergoing elective revascularization from 25 randomized trials were pooled, and outcomes were extracted at the longest available follow-up. The primary endpoint was cardiac death. Secondary endpoints were all-cause death, spontaneous myocardial infarction, any myocardial infarction, and stroke.
The authors found a statistically significant 21% relative risk reduction in cardiac death with revascularization plus medical therapy (risk ratio 0.79, 95% confidence interval 0.67 to 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 in the invasive arm. A trial sequential analysis showed that addition of new trials to current evidence would be unlikely to modify the benefit of revascularization 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 revascularization plus medical therapy (risk ratio 0.74, 95% confidence interval 0.64 to 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.
Overall, this meta-analysis suggests that the benefits of revascularization and optimized medical therapy are additive and their combination is required to achieve maximal and durable prevention of adverse events.