Extended follow-up data out to 15 years show no survival benefit with an initial strategy of PCI plus optimal medical therapy compared with optimal medical therapy alone among patients in the COURAGE trial.
In the main COURAGE trial, results of which were published in 2007, there was no significant difference in the rate of survival during a median follow-up of 4.6 years among 2,287 patients with stable ischemic heart disease at 50 centers randomly assigned PCI plus medical therapy or medical therapy alone.
The new analysis included 53% (n = 1,211) of the original COURAGE population followed for up to 15 years. The investigators used Social Security numbers of patients treated at US VA and some non-VA sites to track survival after the original COURAGE trial period ended and searched the VA national Corporate Data Warehouse and the National Death Index for survival information and dates of death.
Median follow-up duration for the extended follow-up cohort was 11.9 years (range, 0-15).
Twenty-five percent (n = 561) of the overall COURAGE population died over the course of the study: 180 during the original trial period and 381 during extended follow-up. Of those deaths, 25% occurred in the PCI group and 24% in the medical therapy group (unadjusted HR for PCI = 0.98; 95% CI, 0.83-1.15; P = .77). Among the patients with extended follow-up, 41% of those in the PCI group and 42% in the medical therapy group died (unadjusted HR = 0.95; 95% CI, 0.79-1.13; P = .53). Cox regression analysis yielded an HR for death from any cause in the PCI group vs. medical therapy group of 1.03 (95% CI, 0.83-1.21; P = .76).
Further, “no survival benefit with initial PCI could be discerned during the extended follow-up; in addition, no treatment-by-subgroup interactions were detected,” Steven P. Sedlis, MD, from the New York VA Healthcare Network, and colleagues wrote in The New England Journal of Medicine.
The researchers noted that data from the original COURAGE trial suggested that a late survival benefit with PCI may have emerged during extended follow-up, as survival curves indicated a separation at 5 years in favor of PCI (HR for death = 0.87; 95% CI, 0.65-1.13). However, the current data indicate no late trend to suggest a survival advantage.
Several limitations of the new analysis were discussed in the NEJM paper, such as: survival data were only available for 53% of the COURAGE population, which included only a small number of non-VA trial participants and no Canadian participants; the endpoint of death from any cause allowed for no distinction as to whether deaths were cardiac- or noncardiac-related; and older device technologies and pharmacologic treatments were used, as the main trial randomized patients from 1999 to 2004.
“All of these limitations, as well as the relatively high late mortality associated with stable ischemic heart disease despite intensive medical therapy, underscore the importance of the ongoing ISHCEMIA trial,” Sedlis and colleagues wrote.
ISCHEMIA will evaluate the rate of death from CV causes or MI in patients with stable ischemic heart disease assigned to optimal medical therapy plus cardiac catheterization and contemporary revascularization techniques including second-generation drug-eluting stents or optimal medical therapy alone. – by Katie Kalvaitis
Disclosure: Sedlis reports no relevant financial disclosures. See the full study for a list of the other authors’ relevant financial disclosures.