ACC: Meds Equal to Surgery in Ischemic Heart Failure
NEW ORLEANS -- Surgery for ischemic heart failure doesn't save more lives than medical therapy alone, according to the first randomized comparison of these treatments in the modern era.
The trial, conducted among more than 1,200 patients, found that optimal medical therapy alone equalled coronary artery bypass grafting (CABG) for all-cause mortality among patients with coronary artery disease and low ejection fraction (41% versus 36%, P=0.12), reported Eric J. Velazquez, MD, of the Duke Clinical Research Institute in Durham, N.C., and colleagues.
Surgery did reduce cardiovascular deaths and the composite of all-cause deaths or cardiovascular-related hospitalizations, but with questionable relevance in the overall negative trial, the group reported here at the American College of Cardiology meeting.
A substudy from the same trial couldn't pick out which patients benefited more from CABG with cardiac viability imaging.
The reports, from the NIH-sponsored Surgical Treatment for Ischemic Heart Failure (STICH) trial, were published simultaneously online in the New England Journal of Medicine.
Clinical Impact Predicted
"For over 20 years the standard wisdom has been that patients with a weak heart and blocked arteries do better with bypass surgery," ACC meeting co-chair Edward J. McNulty, MD, of the University of California San Francisco and Kaiser Permanente in San Francisco, noted at a press briefing in advance of the meeting.
"However, in the interim medical therapy has improved dramatically," he noted, calling STICH a blockbuster trial with the potential to change practice.
In that regard, the trial is like the COURAGE trial that made waves in cardiology with the finding that optimal medical therapy was every bit as good as stenting for chronic stable angina, agreed Stephanie A. Moore, MD, a heart failure specialist at Massachusetts General Hospital in Boston.
"Medical therapy versus surgical treatment is always a question in our mind," she told MedPage Today. "There are literally hundreds of thousands of patients that undergo surgery for advanced heart failure, and any guidance through randomized controlled trials would provide us with valuable information."
But STICH doesn't provide definitive answers in heart failure, cautioned James C. Fang, MD, of Case Medical Center in Cleveland, in an editorial that accompanied the NEJM studies.
"The trial was a study of ischemic heart disease rather than heart failure per se," he wrote.
Heart failure wasn't required for entry, and the patients differed from typical systolic heart failure populations in being younger (mean age 60), with more angina (more than 60% in both groups) and less severe heart failure (more than 60% with New York Heart Association functional class I or II), Fang noted.
He suggested getting "comfortable with the notion that, in general, surgery is not superior" and provided the following recommendations for practice:
Medical therapy was to follow current clinical guidelines; all cardiac surgeons involved in the study were experienced in CABG with a documented procedural mortality rate of 5% or less in patients with an ejection fraction of 40% or less.
After an average 56 months of follow-up, the secondary endpoints tended to favor surgery.
Death from cardiovascular causes was less common with CABG compared with medical therapy alone, a finding with borderline statistical significance (28% versus 33%, hazard ratio 0.81, P=0.05).
The composite of death from any cause or hospitalization for cardiovascular cases was also less likely with CABG (58% versus 68%, hazard ratio 0.74, P<0.001).
Other secondary endpoints, with the exception of 30 day mortality, showed similar advantages to CABG.
However, as Fang and the researchers agreed, the relevance of secondary endpoints was questionable in the overall negative trial, given that the primary endpoint was not met.
Furthermore, the cardiovascular death endpoint -- the one most likely to be influenced by CABG -- would not have been significant if adjusted for multiple testing, the researchers noted.
During the trial, 17% of medical group patients crossed over to CABG, typically due to progressive symptoms, acute decompensation, or patient or family decision.
An as-treated analysis considering patients who crossed over within one year to have been in the CABG group showed a significant 30% benefit for the primary endpoint of all-cause mortality with CABG compared with medical therapy alone (hazard ratio 0.70, P<0.001).
A per-protocol analysis excluding crossovers showed a significant benefit to CABG as well (hazard ratio 0.76, P=0.005).
"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," Velazquez's group cautioned in the paper.
Fewer patients crossed over from CABG to medical therapy alone, which may have biased the results against showing a benefit from CABG in the main analysis, the researchers suggested.
Viability of Testing
Myocardial viability testing with single-photon-emission CT (SPECT) computed tomography or dobutamine echocardiography or both couldn't identify a patient group that derived greater benefit from CABG in the substudy, reported by Robert O. Bonow, MD, of Northwestern University in Chicago, at the ACC conference.
In the subset of 601 patients in the trial who had myocardial viability imaging, those with viable myocardium were not less likely to die than those without viable myocardium after adjustment for baseline variables (37% versus 51%, P=0.21).
Viability status did not interact with treatment assignment for mortality impact (P=0.53).
Among subset studied, 303 were randomly assigned to medical therapy alone and 298 had CABG plus medical therapy.
The researchers suggested that it's not that viability doesn't matter -- but perhaps that other variables, such as left ventricular volumes and ejection fraction, may be causally determined by extent of viable heart tissue.
Another concern was that viability testing wasn't randomized and may have been biased by investigator selection of patients.
"The analysis is a strong reminder that in this era of cost-effectiveness, the role of expensive technologies should be accountable to a rigorous study of incremental benefit," Fang noted in his editorial.
Primary source: New England Journal of Medicine
Velaquez EJ, et al "Coronary-artery bypass surgery in patients with left ventricular dysfunction" N Engl J Med 2011; DOI: 10.1056/NEJMoa1100356.
Additional source: New England Journal of Medicine
Bonow RO, et al "Myocardial viability and survival in ischemic left ventricular dysfunction" N Engl J Med 2011; DOI: 10.1056/NEJMoa1100358.
Additional source: New England Journal of Medicine
Fang JC "Underestimating medical therapy for coronary disease ... again" N Engl J Med 2011; DOI: 10.1056/NEJMe1103414.