Invasive Treatment for Stable CAD: Is There a Cardiac Mortality Benefit?

Patients with stable coronary artery disease (CAD) who underwent coronary revascularization had the benefit of decreased cardiac mortality in subsequent years, according to a meta-analysis pooling ISCHEMIA, COURAGE, and other randomized trials.

Cardiac mortality risk was reduced in revascularized patients compared with peers assigned to medical therapy alone (RR 0.79, 95% CI 0.67-0.93), reported Eliano Navarese, MD, PhD, of Nicolaus Copernicus University in Toruń, Poland, at the virtual European Association of Percutaneous Cardiovascular Interventions (EuroPCR) meeting.

"The benefits of revascularization and of optimized medical therapy are additive and the combination is required to achieve maximal and durable prevention of adverse events," Navarese said.

The meta-analysis included 25 trials with 19,806 patients, with longest follow-up averaging 5.7 years. A full manuscript was simultaneously published online in the European Heart Journal.

These findings may offer some redemption for coronary revascularization in stable CAD after the lack of benefit suggested by the recent ISCHEMIA trial, as well as COURAGE from 2007.

Yet the question of the value of coronary artery bypass grafting and percutaneous coronary intervention (PCI) in this setting remains unsettled, said Eric Bates, MD, of University of Michigan in Ann Arbor, who was not involved with Navarese's study.

"Since medical and revascularization therapies continue to improve, the unanswered question remains whether revascularization with greater use of arterial grafts and PCI with newest-generation stents reduces death or MI in patients on medical therapy including SGLT2 inhibitors and PCSK9 inhibitors when appropriately prescribed," he told MedPage Today.

"After COURAGE was published, some in the interventional community pushed back with different analyses and opinion pieces to try to discredit the findings that revascularization did not reduce the risk of death or MI in patients with stable CAD, a finding that was found before and after COURAGE and one that is not in dispute," Bates said.

Now, he added, the same thing is happening after ISCHEMIA.

During the EuroPCR session, Navarese noted that the magnitude of risk reduction in cardiac mortality was associated with duration of follow-up: the benefit of coronary revascularization increased progressively over time, such that there was an incremental reduction in cardiac death for every 4 years of additional follow-up (RR 0.81, 95% CI 0.69-0.96).

"Remarkably, the totality of inter-trial variance in cardiac mortality was attributable to variability in length of follow-up (R²=100%). Thus, the magnitude of cardiac mortality reduction appeared to be a function of both revascularization and follow-up duration," Navarese and co-authors wrote.

The difference in cardiac mortality between groups was also related to the lower risk of spontaneous MI (RR 0.74, 95% CI 0.64-0.86) after revascularization, "offering a mechanistic understanding of the underpinnings for the cardiac death reduction observed with revascularization plus medical therapy compared with medical therapy alone," they noted.

The secondary endpoint of all-cause death was no different between revascularization and medical therapy groups (RR 0.94, 95% CI 0.87-1.01).

However, the investigators removed a study with a very high rate of crossover from medical therapy to revascularization -- 66% -- and found this tilted the mortality analysis in favor of revascularization (RR 0.90, 95% CI 0.83-0.99), Navarese said.

Rates of stroke and any MI stayed similar between groups.

The investigators acknowledged that they did not have patient-level data for the analysis. Moreover, the analysis was limited by the heterogeneity in stents used in each included study.

Findings regarding cardiovascular death and spontaneous MI in the meta-analysis "can only be hypothesis-generating, since these endpoints were not designated endpoints in the trials," Bates warned.

The degree to which complete revascularization can be linked to outcomes -- a point raised by ISCHEMIA investigators in recent weeks -- is another important hypothesis that needs to be tested in a randomized study, he added.

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