Door Shut on Excess Noncardiac Deaths After Intervention for Stable CAD

PARIS — Cardiologists were reassured that coronary revascularization does not increase noncardiac mortality in people with chronic coronary syndrome, based on a meta-analysis reported here at EuroPCR.

Across 18 trials, revascularization by percutaneous coronary intervention or bypass surgery did not change noncardiac mortality rates over an average follow-up of 5.7 years in studies in stable ischemic heart disease or chronic coronary syndrome (RR 1.09, 95% CI 0.94-1.26).

The lack of effect did not vary according to length of follow-up, and trial sequential analysis suggested that final evidence has been reached such that “adding further studies is not going to add information content,” according to William Wijns, MD, MPH, of National University of Ireland in Galway.

A full manuscript of the meta-analysis was published simultaneously in JACC: Cardiovascular Interventions.

Wijns told the audience that the analysis was prompted by the ISCHEMIA EXTEND trial which had shown lower 7-year cardiovascular mortality with early intervention (6.4% vs 8.6%, adjusted HR 0.78, 95% CI 0.63-0.96) being offset by higher noncardiovascular mortality (5.6% vs 4.4%, adjusted HR 1.44, 95% CI 1.08-1.91).

At publication, that group had acknowledged that excess noncardiovascular deaths had come from an underpowered analysis and they could not offer a mechanistic explanation. Causes of noncardiovascular death were predominantly malignancy, despite groups sharing a similar baseline prevalence of malignancy.

Session chair Davide Capodanno, MD, PhD, of University of Catania in Italy, recalled the “creative” ways — related to more rehospitalizations and more infections, for example — that some have tried to explain the signal of noncardiac deaths in the intervention arm.

“This is a good use of a meta-analysis,” and it closes the door on a controversy, Capodanno said.

All is not settled, however, as there is still debate on whether revascularization trials should continue to separate cardiac and noncardiac deaths, a discussion that has been ongoing for years, commented fellow panelist Michael Joner, MD, of German Heart Centre Munich.

Wijns said he favored reporting cardiac mortality as a primary endpoint going forward in these studies. “As the outcomes of intervention … are getting better, if you go for all-cause mortality, you’re likely to give more weight to these events that have nothing to do with the procedure you’re looking at,” he explained.

Gregory Ducrocq, MD, PhD, of Hôpital Bichat-Claude Bernard in Paris, pointed out that adjudicating deaths outside of the hospital is tricky and the default is to give them the label of noncardiac death when there is insufficient information.

“I agree with notion we should be looking at cardiac mortality,” said Haitham Amin, MD, of Mohammed Bin Khalifa Cardiac Center in Awali, Bahrain, who added that his digital monitoring of the EuroPCR audience response showed participants tended to agree with the opinions of Wijns and other panelists.

An earlier meta-analysis had confirmed that elective coronary revascularization at least reduces cardiac mortality over conservative therapy alone.

Focusing on noncardiovascular mortality instead, Wijns and colleagues conducted a new pooling of randomized trials directly comparing coronary revascularization vs medical therapy alone in over 16,000 people. Investigators detected no heterogeneity among the 18 trials included (e.g., COURAGE, ISCHEMIA, ORBITA).

Notably, the robustness of the finding of no difference in noncardiac mortality rates persisted across various sensitivity analysis — random effects, without ISCHEMIA, Bayesian, mixed-effects Poisson, without bypass surgery, and without chronic total occlusions, Wijns reported.