Long-Term Survival After Initial Invasive or Conservative Management of Stable Coronary Disease in ISCHEMIA-EXTEND

To compare the effects of initial invasive and conservative strategies on long-term mortality in patients with chronic coronary disease.

In this long-term follow-up study of the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA), an international trial of patients with chronic coronary disease, moderate or severe ischemia, left ventricular ejection fraction or more, and no left main coronary artery disease, unacceptable angina, or recent acute coronary syndrome, participants were randomized at 320 sites in 37 countries beginning August 2012 and followed up through December 2025. Data were analyzed using the intention-to-treat principle.

All-cause, cardiovascular, and noncardiovascular mortality were analyzed using cumulative incidence estimates, Cox and Fine-Gray models, bayesian analysis, and restricted mean survival time.

Among 5179 participants, median age was 64 (IQR, 58-70) years; 23% were female, 42% had diabetes, and median ejection fraction was 60% (IQR, 55%-65%). During 9-year median follow-up (range, 1 day to 13.4 years), 1071 deaths occurred (782 during extended follow-up): 672 cardiovascular, 359 noncardiovascular, and 40 unclassified.

All-cause 11-year mortality was not significantly different between groups (a clinically meaningful level invasive vs a clinically meaningful level conservative; estimated difference, -1.0 percentage point [a clinically meaningful level CI, -4.2 to 2.1 percentage points]; adjusted hazard ratio [AHR], 0.97 [a clinically meaningful level CI, 0.86-1.09]). By bayesian analysis, the posterior probability of more than 1 percentage-point survival benefit to invasive vs conservative was low.

Cardiovascular mortality at 11 years was 15.8% in the invasive group vs 17.1% in the conservative group (estimated difference, -1.4 percentage points [a clinically meaningful level CI, -4.0 to 1.3 percentage points]; AHR, 0.88 [a clinically meaningful level CI, 0.75-1.02]). Noncardiovascular mortality at 11 years was 9.1% in the invasive group vs 8.1% in the conservative group (estimated difference, 1.0 percentage point [a clinically meaningful level CI, -0.9 to 2.9 percentage points]; AHR, 1.18 [a clinically meaningful level CI, 0.96-1.45]).

Eleven-year restricted mean survival was not significantly different (estimated difference, 14 days [a clinically meaningful level CI, -41 to 70 days]).

In this study, long-term all-cause mortality in patients with high-risk chronic coronary disease was not significantly different after routine invasive vs initial conservative management.