STICH: CABG Does Not Extend Survival Over Medical Therapy in Heart Failure Patients

NEW ORLEANS, LA—Adding coronary artery bypass graft (CABG) surgery on top of medical therapy does not reduce all-cause mortality in patients with left ventricular dysfunction over long-term follow-up, according to results from the STICH trial presented April 4, 2011, at the American College of Cardiology Scientific Session/i2 Summit. But the fact that the study failed to meet its primary endpoint did not deter enthusiasm over CABG.

A subanalysis of the STICH (Surgical Treatment for Ischemic Heart Failure) trial presented in the same session, meanwhile, showed that the presence of viable myocardium did nothing to increase survival or help differentiate which patients might benefit from surgical intervention.

Both studies were simultaneously published online ahead of print in the New England Journal of Medicine.

Hints That CABG Could Be Superior

To better establish the role of CABG in treating patients with coronary disease and heart failure Eric J. Velazquez, MD, of Duke University Medical Center (Durham, NC), and colleagues enrolled 1,212 CAD patients with an ejection fraction of 35% or less who were amenable to CABG at 127 clinical sites in 26 countries. Subjects were randomized to receive medical therapy with (n = 610) or without CABG (n = 602). Baseline characteristics were well balanced between the 2 groups.

At a median follow-up of 56 months, the primary endpoint of all-cause death was numerically higher with medical therapy alone, but the difference did not reach statistical significance. Secondary endpoints including cardiovascular death and the composite of all-cause death and hospitalization for cardiovascular causes, however, favored CABG over medical therapy (table 1).

Table 1. Long-Term Outcomes

^a Primary endpoint.

“As anticipated, CABG had an early risk that took 2 years to abate,” Dr. Velazquez added.

Over the course of the study, 17% of patients in the medical therapy group and 91% of the surgery group had undergone CABG. The researchers performed an analysis comparing patients who were treated with medical therapy throughout the first year and those who underwent CABG, whether as the assigned treatment or because of crossover. In this comparison, CABG significantly reduced the likelihood of all-cause death (HR 0.70; 95% CI 0.58-0.84; P < 0.001). A per-protocol analysis of patients who underwent their assigned treatments showed similar results.

“The adjusted, as treated, and per protocol analyses of the primary endpoint, although informative, should be considered provisional, as they were not the intention-to-treat analysis,” Dr. Velazquez cautioned.

STICH's results hold important implications for clinical practice, he said. “For patients with heart failure, coronary disease should be assessed and medical therapy optimized for all patients. Decision making for CABG is complex and should be individualized. Now with results from the STICH trial, patients should be informed of the short-term risk [that might be exchanged] for a potential long-term benefit.” Additional information will be provided by 10-year follow-up, he reported.

Panelist Bernard Gersh, MB, ChB, of the Mayo Clinic (Rochester, MN), characterized STICH as “an incredible trial, a stunning achievement.”

“We have known for decades that in patients with LV dysfunction, ischemia is the major cause of mortality. And in patients with ischemia, LV dysfunction is the major cause of mortality. You have now proven the concept,” he said.

Contrary to the trial's main finding, Dr. Gersh retained a positive view of CABG. “What's going to be very interesting,” he commented, “will be the analyses that look at mechanisms of benefit. Does surgery work because of an improvement in systolic function? Could it be an improvement in diastolic function? Because ischemia does increase myocardial stiffness. I suspect that much of the improvement will be a benefit in sudden cardiac death. . . . Could it be that the benefit is on recurrent infarction, which these patients obviously cannot tolerate?”

Another possibility is that there may be a patient subset that might benefit from surgery even within the first 2 years, he added. “There will be others where the excess hazard cancelled out the benefit.”

Viability Not a Valid Indicator

Robert O. Bonow, MD, of the Northwestern University Feinberg School of Medicine (Chicago, IL), then shared findings from a prospective substudy of STICH that addressed whether myocardial viability was linked to outcome.

In all, 601 patients in STICH (49.6% of the overall cohort) underwent assessment of myocardial viability via single-photon-emission computed tomography, dobutamine echocardiography, or both. While all study centers were strongly encouraged to perform such testing in every patient, the decision was left up to recruiting investigators. Even so, the treatment arms were well-balanced within the substudy, with 298 of patients randomized to medical therapy plus CABG and 303 to medical therapy alone.

Imaging showed that 487 patients had viable myocardium at baseline and 114 did not. Although death rates were lower in patients with signs of viability (37% vs. 51%; P = 0.003), this association did not persist after adjustment for baseline prognostic variables.

In fact, other variables such as risk score, LVEF, LV end-diastolic volume, and LV end-systolic volume had stronger associations with mortality than did myocardial viability. Moreover, there was no significant interaction between viability status and treatment assignment with regard to mortality (P = 0.53). A per protocol analysis showed similar trends.

“We recognize that patients with ischemic left ventricular dysfunction represent complex management issues and that decisions regarding diagnostic testing and therapeutic interventions need to be individualized,” Dr. Bonow concluded. “However, the lack of interaction between myocardial viability and benefit from CABG in this study indicates that assessment of myocardial viability independent of other relevant variables should not be considered the deciding factor in selecting the best therapy for patients with ischemic left ventricular dysfunction.”

Dr. Gersh responded by saying “if you're not confused by this, you're not thinking clearly, because I'm confused right now. The first presentation provided us with the answers, and now [Dr. Bonow has] raised a lot of new questions.” Among them are the best way to measure myocardial viability and whether there is a cutoff for how much viability is enough, he said.

The overall STICH trial is “very positive,” Dr. Gersh commented, but he questioned how clinicians should know which patients to refer for CABG, since viability was not informative.

Who Gets CABG?

Dr. Bonow replied that there are other clinical and anatomic variables to consider. “There could be subsets here that we have not yet analyzed, where [myocardial viability] could be important,” he added, even if across the board it is not.

Panelist Steven F. Bolling, MD, of the University of Michigan Health System (Ann Arbor, MI), agreed that there are other criteria that may be used, such as the presence of distal targets and a patient's surgical risk. “Now myocardial viability in these patients with heart failure and left ventricular dysfunction may not be the number 1 criteria by which we send patients to the operating room. And in fact it appears patients, whether they have viability or not, benefit from coronary bypass,” he said, also referring to the STICH trial as “positive.”

After both of the presentations, however, session co-chair Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), reemphasized that, technically speaking, STICH was a negative trial.

“I am fascinated that my esteemed colleagues, Dr. Gersh and Dr. Bolling, are seeing the first presentation as being so positive given that the primary endpoint had a P value of 0.12. The investigators themselves say it did not meet its endpoint of showing a difference in mortality, although I will say that overall when you look at the tapestry of the trial, it seemed to be a little bit more positive than negative,” Dr. Stone concluded. “But I think it's hard to declare STICH as a strongly positive trial.”

Coming from that background, he added, the substudy should “not throw a complete blanket over the viability hypothesis.”

 

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Sources:
1. Velazquez EJ. Medical therapy with or without coronary artery bypass graft surgery in patients with ischemic cardiomyopathy: Results of the Surgical Treatment of Ischemic Heart Failure trial. Presented at: American College of Cardiology Annual Scientific Session/i2 Summit; April 4, 2011; New Orleans, LA.

2. Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;Epub ahead of print.

3. Bonow RO. Influence of myocardial viability on outcome of patients with coronary artery disease and left ventricular dysfunction undergoing medical therapy with and without surgical revascularization: Results of the Surgical Treatment of Heart Failure trial. Presented at: American College of Cardiology Annual Scientific Session/i2 Summit; April 4, 2011; New Orleans, LA.

4. Bonow RO, Maurer GM, Lee KL, et al. Myocardial viability and survival in ischemic left ventricular dysfunction. N Engl J Med. 2011;Epub ahead of print.

5. Fang JC. Underestimating medical therapy for coronary disease . . . again. N Engl J Med. 2011;Epub ahead of print.

 

 

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