NEW ORLEANS--In heart failure (HF) patients with coronary artery disease (CAD) on medical therapy, CABG should now be considered to reduce cardiovascular mortality and morbidity, as patients have similar outcomes to contemporary medical therapy, concluded the researchers of the STICH trial presented April 4 as a late-breaking clinical trial at the 60th annual American College of Cardiology (ACC) conference.
CAD is the major substrate for HF and left ventricular dysfunction (LVD). However, prior to this trial, the role of CABG surgery in patients with CAD and HF has not been “clearly established,” said Eric J. Velazquez, MD, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.
In the 1970s, randomized controlled trials of CABG versus medical therapy for chronic stable angina excluded patients with LVD (left ventricular ejection fraction of less than 35 percent), and only 4 percent of the patients were symptomatic with HF, Velazquez explained. “Since the 1970s, major advances in surgical care and medical therapy for CAD, HF and LVD render previous limited data obsolete for clinical decision making,” he said. Recent observational analyses suggest a role for CABG for HF which is increasingly utilized, yet substantial clinical uncertainty remains.”
In STICH (Surgical Treatment for Ischemic HF Trial), the researchers posed the surgical revascularization hypothesis that in patients with HF, LVD and CAD amenable to surgical revascularization, CABG added to intensive medical therapy will decrease all-cause mortality compared to medical therapy alone.
The primary endpoint of the randomized controlled, non-blinded trial, which had 99 clinical sites in 22 countries, was all-cause mortality. The major secondary endpoints included cardiovascular mortality and death (all-cause) plus cardiovascular hospitalization.
The investigators randomized 602 patients to medical therapy alone and 610 to CABG.
After an average of nearly five years of follow-up, they found that bypass surgery reduced the risk of death from any cause by 14 percent when compared to medical therapy; however, it was not statistically significant.
“We were unable to show a significant benefit for CABG in our primary analysis, but if you dive deeper, the data are much more supportive of bypass surgery,” said Velazquez. “This information fills an important gap in how we should evaluate the opportunity for CABG in these patients.”
Bypass surgery also reduced the risk of cardiovascular death by 19 percent and the combined risk of death from any cause plus hospitalization for heart disease by 26 percent—both of which were statistically significant.
Fifty-five patients who were assigned to the surgery group never actually had the procedure, whereas 100 who were assigned to medical therapy eventually had CABG. When researchers analyzed the data only on patients who had their assigned treatment, they found that bypass surgery reduced the risk of death from any cause by 25 percent. Similarly, when they analyzed the data according to the treatment patients actually had, including the “crossovers” into the opposite group, they found that bypass surgery reduced the risk of death from any cause by 30 to 50 percent.
Researchers noted that bypass surgery had a higher upfront risk than medical treatment alone. In fact, it was only after two years that survival was better with bypass surgery.
“Although we believe that these results are informative, since they mirror real-world clinical decision making, in which the choice of CABG is not influenced by randomization, these per-treatment analyses must be interpreted conservatively,” the researchers wrote in the New England Journal of Medicine.
“It will be interesting to see the mechanism that leads to benefits, which will be interesting to track in the follow-up analysis,“ said Bernard J. Gersh, MD, PhD, interventional cardiologist at Mayo Clinic in Rochester, Minn., who called it a “landmark study with incredible results.” Gersch was one of the trial’s discussants.
Specifically, Velazquez said that their future analysis would focus on early hazard, as well as early stroke hazard.
Also, Velazquez acknowledged that the surgery outcomes were “very good” and the adherence to medical therapy was also higher than in real-life clinical situations, so there may be some differences in real-world clinical practice.
The National Heart, Lung and Blood Institute