Updated– After a very long wait, the Surgical Treatment for Ischemic Heart Failure (STICH) trial has finally shed light on the common but poorly understood use of CABG in heart failure patients with ischemic heart disease. The results were presented by Eric Velazquez at the ACC and published simultaneously in the New England Journal of Medicine.
1212 patients with EF < 35 and coronary artery disease were randomized to CABG or medical therapy. At 56 months median followup the death rate (the primary endpoint of the study) was 41% in the medical therapy group versus 36% in the CABG group (HR with CABG 0.86, CI 0.72-1.04, p=0.12).
- Cardiovascular death occurred in 33% of the medical therapy group versus 28% of the CABG group (HR 0.81, CI 0.66-1.00, p=0.05).
- The rate of death plus hospitalization for cardiovascular causes was 68% in the medical therapy group versus 58% in the CABG group (HR 0.74, CI 0.64-0.85, p<0.001).
100 patients in the medical therapy group ended up having CABG during the 56 month followup period. 555 patients in the CABG group actually underwent surgery.
With the exception of 30 day mortality, other secondary clinical outcomes favored CABG. As expected, CABG resulted in an early risk, so that for the first two years after randomization the risk of death was higher in the surgical group.
The investigators had initially planned to enroll 2000 patients, but slower than desired enrollment led them to adjust the trial, so that fewer patients were followed for a longer period in order to accumulate enough endpoints.
The authors cautioned that “when the analysis in any trial fails to detect a significant difference between treatment groups with respect to the primary outcome, analyses of secondary outcomes showing a benefit must inevitably be considered to be somewhat provisional.”
STICH Myocardial Viability Substudy
A myocardial viability substudy was presented immediately following the main study and was also published simultaneously in the New England Journal of Medicine. First author Robert Bonow said that physicians often use myocardial viability tests to determine whether patients with coronary artery disease and LV dysfunction should undergo CABG, but that this strategy has never been tested.
In the substudy, 601 patients who had already undergone myocardial viability testing were randomized to either CABG or medical therapy. The death rate was 37% among the 487 patients with viable myocardium and 51% among the 114 patients without viable myocardium (HR for patients with viable myocardium 0.64, CI 0.48-0.86, p=0.003). However, this association lost all statistical significance after adjustment for other baseline characteristics.
The authors write that their results indicate “that assessment of myocardial viability alone should not be the deciding factor in selecting the best therapy for these patients.”
James Fang, in an accompanying editorial entitled “Underestimating Medical Therapy for Coronary Disease… Again,” writes that patients like those enrolled in the STICH trial should receive aggressive medical therapy and that revascularization “should be carefully weighed but can be safely deferred,” though it should be offered to those with “persistent or progressive symptoms.”
Update: I just want to offer a brief update to the news story above, which was based on the NEJM publications. Velazquez’s presentation at the late-breaker session was much more emphatically pro-CABG, and emphasized a number of secondary analyses and trends which favored CABG. One of the discussants, Bernard Gersh, said STICH was a strongly positive trial, but he was criticized by session co-chair Gregg Stone, who urged caution about this interpretation of the trial and reminded the audience that the trial was technically a negative trial.
Here is a press release from Duke University:
Bypass Surgery Should be Considered for Some Heart Failure Patients
DURHAM, NC – The first study to compare contemporary approaches to surgery and medical therapy for heart failure caused by clogged coronary arteries found coronary bypass surgery should be considered in addition to medical therapy, according to researchers at Duke Clinical Research Institute. The findings were presented today at the American College of Cardiology’s Annual Scientific Session and simultaneously published online in the New England Journal of Medicine.
“This is the first study in over three decades to provide important insight into the care of high risk heart failure patients with coronary disease who are candidates for bypass surgery in the setting of modern medicine,” said Eric J. Velazquez, M.D., the study’s lead author and an associate professor of medicine at Duke University Medical Center. “These patients are often overlooked as candidates for coronary bypass surgery, but our results suggest that when done in combination with optimal medical therapy, surgery can reduce the risk of death and hospitalization.”
Nearly 6 million people in the United States have heart failure and approximately two-thirds can be attributed to clogged coronary arteries that impair the heart’s ability to pump blood and oxygen.
The STICH (Surgical Treatment for Ischemic Heart Failure) trial is the largest study to compare outcomes among patients who had coronary artery bypass grafting (CABG) while taking guideline-recommended medications compared to those taking medication alone.
Previous smaller studies had been conducted prior to major developments in medical therapy and cardiac surgery that have led to current treatment guidelines.
After nearly five years of follow-up, researchers found that bypass surgery reduced the risk of death from any cause by 14 percent when compared to medical therapy alone, although the finding was not statistically significant (P=.123).
Bypass surgery significantly reduced the risk of cardiovascular death by 19 percent (p=0.05) and the combined risk of death from any cause plus hospitalization by 26 percent (p<0.001).
“These findings have the potential to change clinical practice,” Velazquez said. “The current approach for making treatment decisions for many heart failure patients today either ignores the potential treatable contribution of coronary artery disease or, if it is discovered, places them on an express train toward surgery. This study finally provides doctors and patients with the necessary details to have informed discussions about the potential risks and benefits, to optimize medical therapy and determine if or when bypass surgery should be considered.”
Velazquez added, “STICH should give physicians and patients comfort that decisions about surgery should not be avoided but do not need to be rushed. In other words, the message should be: take the local train.”
STICH is a multi-center, international clinical trial that enrolled 2,136 patients between July 2002 and May 2007. The study reported today included 99 medical centers in 22 countries that recruited patients with heart failure caused by coronary artery disease or a previous heart attack. Researchers randomly assigned 602 patients to optimal medical therapy alone and 610 patients to coronary bypass surgery plus optimal medical therapy.
When researchers analyzed the data on patients based on the treatment assigned by the study, not accounting for those who “crossed over” from the group for which they were originally randomized, 40 percent of people in the medical therapy group had died after five years compared to 35 percent among those who had surgery. When the crossovers were included in the analysis, patients who received bypass surgery had a 30 percent lower rate of death compared to those that remained on medical therapy alone. The researchers note that the total number of deaths was higher in the surgical group than in the medical therapy group for up to two years after randomization.
“Until now the role of CABG in patients with coronary artery disease and heart failure has not been clearly established,” said Robert H. Jones, M.D., study co-author and professor of surgery at Duke. “While there is an early hazard associated with surgery, optimal medical therapy in conjunction with surgery can be performed safely in this high risk patient population and should be considered, especially for patients with potentially longer time horizons.”
Previously reported data from STICH found that a surgical procedure to resize an enlarged, weakened heart muscle during coronary bypass surgery for heart failure adds cost and risk but doesn’t offer patients any additional benefit when compared with those who received a bypass procedure alone.
The STICH trial has been extended for an additional five years to continue to follow the patients enrolled.
The trial was sponsored by the National Heart, Lung, and Blood Institute (NHLBI). Additional support was provided by Abbott Laboratories, which had no role in the conduct or reporting of the trial.
Study co-authors include Kerry L. Lee, Marek A. Deja, Anil Jain, George Sopko, Andrey Marchenko, Imtiaz S. Ali, Gerald Pohost, Sinisa Gradinac, William T. Abraham, Michael Yii, Dorairaj Prabhakaran, Hanna Szwed, Paolo Ferrazzi, Mark C. Petrie, Christopher M. O’Connor, Pradit Panchavinnin, Lilin She, Robert O. Bonow, Gena Roush Rankin, and Jean-Lucien Rouleau.