CABG Beats Medical Therapy in CAD Patients With Severe LV Dysfunction: STICH 10-Year Results

CHICAGO, IL—It took 10 years, but long-term follow-up from the STICH trial now demonstrates a survival benefit for surgical revascularization on top of best medical therapy as compared with medical therapy alone in patients with heart failure, severe left ventricular dysfunction, and coronary disease amenable to treatment.

Landmark trials establishing a role for CABG date back 40 years and excluded patients with severe LV dysfunction. STICH (Surgical Treatment for Ischemic Heart Failure) was the first trial to formally look at CABG in this group but found no benefit of bypass over medical therapy at approximately 5 years.

Eric Velazquez, MD (Duke Clinical Research Institute, Durham, NC), presented the results earlier this week at the American College of Cardiology 2016 Scientific Sessions. They were published simultaneously in the New England Journal of Medicine.

Speaking with TCTMD, Velazquez pointed out that the data supporting CABG in patients with heart failure and significant left ventricular dysfunction are dismal, since patients with severe, disabling heart failure had typically been excluded from clinical trials. STICH, which struggled for many years to enroll enough patients, was widely expected to deliver conclusive evidence that CABG was beneficial, but it came up short.

Nonprespecified analyses over the years, from STICH and other trials, have hinted at a benefit in patients with coronary artery disease and severe heart failure, leading to an increase in referrals for CABG for patients with severe LV dysfunction and disabling angina. But many others with severe heart failure who do not complain of coronary artery disease symptoms may simply not be considered for CABG. 

As such, says Velazquez, “There may be a large population of patients who may not be offered or even evaluated for coronary disease or offered CABG because of the current perspectives in the literature.”

A STICH in Time

STICH enrolled a total of 1,212 patients between 2002 and 2007 who had ejection fractions of 35% or less and coronary artery disease that could be treated with bypass surgery. Of note, the trial specifically sought to enroll patients with no or minimal angina symptoms. Patients were randomized to CABG or optimal medical therapy (610 vs 602) and followed for the primary endpoint of death from any cause. As noted, in the main analysis (at a median of 56 months), there was no difference between groups, although subset analyses appeared to favor CABG. In the current analysis, Velazquez and colleagues looked at the STICH outcomes over an additional 5 years: the STICH Extension Study (STICHES).

At 10 years, 58.9% of patients in the CABG group and 66.1% of patients in the medical therapy group had died (P = 0.02). Just over 40% of patients in the CABG group and 49% in the medical therapy group had died of cardiovascular disease (P = 0.006). Looking at the secondary endpoint of all-cause death or hospitalization for cardiovascular causes, results again favored the CABG-treated patients (76.6% vs 87.0%, P < 0.001).

“CABG was associated with more favorable results than medical therapy alone across all clinically relevant long-term outcomes we evaluated,” the authors write. They point out that CABG was associated with a significantly increased risk within the first 30 days and that this increased hazard continued out to 2 years. “Thus,” they say, “it appears that the operative risk associated with CABG is offset by a durable effect that translates into increasing clinical benefit to at least 10 years.”

The Light Shines Brighter

Commenting on the study for TCTMD, Clyde Yancy, MD (Northwestern Memorial Hospital, Chicago, IL), stressed that “for many years, we had no evidence base to support an empiric practice that many physicians follow, which was that for patients with multivessel disease and reduced LV dysfunction to whatever extent, bypass surgery was the preferred strategy. Thankfully the STICH investigators came together to really say, we need to challenge this question.”

Now, with the 10-year data, “I think the light is beginning to shine brighter, and it could be that STICH actually was a positive trial,” Yancy continued. “But we've had to learn the hard way” just what the natural history is for these patients, regardless of what treatment they’ve received, he added.

Some people were transplanted, some people got LVADs, and notably, more than half of all patients in both treatment arms had died, Yancy noted. “So we are really talking about a survival benefit seen in very few patients, and you’ve reinforced the [understanding of the] malignancy of reduced LV function in CAD, regardless of how it’s been treated,” he added. “At some point in our discovery process, we need to find a fundamentally different way of dealing with concomitant severe LV dysfunction in coronary artery disease, because what we have available now—revascularization and medical therapy—at best attenuates the risk of death but doesn’t forestall it as much as we would like to see for our patients.”

Also commenting on the study, Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Medical Center, New York, NY), called the data “critically important because they unequivocally support the revascularization hypothesis in a high-risk group of patients.”

Kirtane, like Yancy, congratulated the authors for committing to follow the patients out to 10 years, and for achieving 98% follow-up for the original cohort. “This now provides definitive evidence of a survival benefit for revascularization over medical therapy in population of patients with stable ischemic heart disease who were treated with excellent medical therapy,” Kirtane said in an email.

Velazquez believes the findings have immediate relevance for patients, saying that there may be “millions of patients with heart failure and left ventricular dysfunction who never even get evaluated for CAD. And for the first time, we have a treatment that actually improves mortality.” Going forward, he said, the implications from STICH are that “we need to look for CAD in patients with LV dysfunction, and if it exists, we need to talk to them about the early mortality risk of CABG”—which remains approximately 5%—“and the long-term benefits.”

In an accompanying editorial, Robert Guyton, MD, and Andrew Smith, MD (Emory University School of Medicine, Atlanta, GA), note that the 2012 ACC/AHA guidelines for CABG state that “it might be considered with the . . . intent of prolonging survival,” a class IIb recommendation, in patients with coronary disease and LVEF < 35%.

The new information, however, supports revising that recommendation to IIa, as “probably beneficial,” they write.

What About a Percutaneous Approach?

A separate question is what the implications may be for PCI, which in the years since STICH started enrollment has gradually become a preferred option across multiple subgroups of CAD patients.

“I think the issue that the FREEDOM trial brought up is, is there not a fundamental difference in the kind of revascularization with surgery than with PCI?” Yancy speculated. “I am fascinated by the notion that regardless of morbidity, regardless of cost, that there may be fundamentally different kinds of revascularization when we talk about surgery versus PCI. That, I think, is still worth additional pursuit, because we know that the market dynamic is trending decidedly in favor of percutaneous revascularization, almost for every coronary disease substrate there is, with the exception of that of almost prohibitive risk, and even some of them are still getting PCI. So we need to continue doing more study.”

Velazquez pointed out that the guidelines are “totally silent” on PCI in low ejection fraction patients. “When you look at the observational cohorts that have compared PCI and CABG in this group . . . you do see a signal of benefit with CABG vs PCI, but those also are dated. So it’s speculation whether PCI would be of benefit,” he said. Whereas surgery has “the early upfront risk and long-term gain, PCI has lower short-term risk, but it’s not known whether it would have similar long-term gain.” Low LVEF patients have such low cardiac reserve, it’s possible that restenosis would be more lethal in this group than in others without severe dysfunction, “so that would be need to be evaluated,” he agreed.

Asked whether this is something STICH investigators and others are considering, Velazquez acknowledged that “forces are gathering” to consider such a trial.

Kirtane told TCTMD that he is involved in OPTIMUM, a multicenter registry of PCI for high-risk patients “turned down” for surgery that will launch later this year that may also help address the question of PCI in ischemic cardiomyopathy and low ejection fraction.

“Although the trial does not specifically address PCI, and we should therefore be circumspect in over-extrapolating these data, there are many patients who are either too high risk for CABG or who do not want to undergo a more invasive surgery,” Kirtane said. “These data provide indirect evidence that complete revascularization, irrespective of modality, in this patient population has great potential to improve these patients’ outcomes.

In the meantime, the results of STICH “should change our clinical approach to patients with heart failure,” the NEJM editorialists write. “These findings should prompt strong consideration of coronary bypass as an addition to medical therapy in shared decision making with these patients.”

 

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Sources:

 

 

• Velazquez EJ, Lee KL Jones RH, et al. Coronary –artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med. 2016;Epub ahead of print.  
• Guyton RA, Smith AL. Coronary bypass—survival benefit in heart failure. N Engl J Med. 2016;Epub ahead of print.