ACC 2009: Stiched Up: Final Results for "Hypothesis Two" Show No Benefits of LV Reconstruction Over CABG Alone

Shelley Wood

March 29, 2009

March 29, 2009 (Orlando, Florida) — The firm belief, by some, that surgically reshaping the left ventricle is the best way to improve outcomes in patients with heart failure caused by coronary artery disease has now decisively unraveled with new results of the Surgical Treatment for Ischemic Heart Failure (STICH) trial. As researchers reported here at the American College of Cardiology 2009 Scientific Sessions, results from "hypothesis two" in STICH, comparing surgical ventricular reconstruction (SVR) on top of CABG with CABG alone, show that the additional surgery successfully reduced the LV volumes but had no impact on symptoms, exercise tolerance, deaths, or cardiac hospitalizations.

The study was simultaneously published online in the New England Journal of Medicine [1].

"The findings of this study do not support the use of SVR in the population studied," Dr Robert H Jones (Duke University, Durham, NC) and colleagues conclude in their paper.

As previously reported by heartwire , STICH, launched in 2002, has been plagued from the start with shifting leadership, debate over the trial design, protocol amendments, and sluggish enrollment. Rather than testing novel approaches, the trial was an attempt to work backward to determine which of three mature strategies already widely in use represented the best form of management for ischemic HF patients: CABG alone, CABG plus SVR, or best medical therapy. Results for the comparison of CABG vs medical therapy (hypothesis one) are still at least two years away: this arm has faced even tougher challenges with enrollment.

Hypothesis two, on the other hand, has faced different challenges, not the least of them being a passionate group of surgeons who have long believed that anatomically reducing LV volumes would translate into better heart function. Interviewed in 2004, trial investigator Dr Lorenzo Menicanti, whose San Donato Hospital, in Milan, Italy, is a world-renowned teaching site for the SVR procedure, told heartwire that he expected SVR to prove superior, because he had seen, in his own patients, major improvements. Likewise, Dr Vincent Dor (Centre Cardio-Thoracique de Monaco), who pioneered the surgery (it is sometimes referred to as the Dor procedure), contributed to the development of the STICH trial but said he struggled to enroll patients because he was already convinced of SVR's benefits and didn't want to risk having patients randomized to CABG or medical therapy alone.

It's Come Undone

STICH hypothesis two ended up enrolling 1000 patients with coronary disease suitable to CABG surgery, an ejection fraction of 35% or less, and dominant anterior LV dysfunction suitable for SVR. The SVR procedure, performed either on- or off-pump, involved an anterior left ventriculotomy centered in the zone of anterior asynergy, a suture encircling the scar, then a cinching of the suture to bring the healthy portions of the ventricular walls in contact with one another. Following randomization and subsequent surgeries, patients were followed for a median of 48 months.

As Jones showed during a late-breaking clinical-trials session, SVR in 501 patients successfully reduced end-systolic volume index to a greater degree than did CABG surgery in the remaining 499 patients (19% vs 6%). But the surgical reshaping had no effect on improvement in angina and heart-failure symptoms or on six-minute walk test, all of which improved to a similar degree in both groups. Rates for the primary outcome of death from any cause combined with cardiac hospitalizations were also almost identical between the CABG and CABG/SVR groups, at 59% and 58%, respectively. Fatal events and cardiac hospitalizations were again mirrored between the two groups.

Dr Dan Mark (Duke University), who presented the quality-of-life end points for STICH, pointed out that SVR was considerably more expensive than CABG alone--roughly $14 000 per patient--yet yielded no additional benefits.

"Bottom line, we looked at a variety of end points associated with quality of life . . . including heart-failure-specific quality of life, and found no evidence that patients who receive SVR on top of CABG were in any way better or were in any way different, out to three years," Mark said.

Picking Apart STICH

Speculating on the possible reasons for the failure of SVR, despite numerous studies pointing to benefits with this approach, the authors hypothesize that experienced surgeons may have randomized only patients in whom SVR seemed less necessary, choosing to ensure that patients who they truly believed might benefit could get SVR directly, rather than risk randomization to the non-SVR groups.

Commenting on the STICH results, Menicanti told heartwire that only 20% of patients eligible for this procedure were actually randomized. "This means that surgeons in 80% of eligible patients were convinced that SVR was the best treatment, and they put patients in the trial when the therapeutic option was not so clear," he said.

But Jones, speaking with the press, stressed that while investigators will now be combing through the data, looking for subsets that may have derived more benefit from SVR, "there is nothing right now to suggest that we can pick out any particular patient who would benefit from this procedure."

Another "more plausible" theory for the trial's neutral findings, raised by investigators in their paper, is that the benefits of reducing LV volume are "counterbalanced by a reduction in diastolic distensibility."

Regardless of the reasons, STICH watchers who have long hoped to get some kind of decisive answers for how to manage HF patients with coronary artery disease will now need to wait for the CABG-vs-medical-therapy arm of the trial. Despite the fact that recent trials such as OAT and COURAGE have supported a role for medical therapy alone--albeit in different patient populations--many physicians are already convinced that revascularization is superior to drugs alone in patients with heart failure related to CAD. A total of 1212 patients were randomized in this arm of the trial; results are expected in 2011.

Menicanti, for his part, said that he thinks the STICH was "the most important surgical trial in the history of the medicine."

In all, 127 surgical teams in 26 countries demonstrated that "even in centers with relatively small experience, SVR can be performed safely with a standardized technique, even if there are differences according with geographic location of the centers.

"This report is only the first step toward a more complete knowledge of the best treatment of ischemic patients with a dysfunctioning left ventricle," Menicanti concluded.

STICH was funded by the National Heart, Lung, and Blood Institute . Jones lists no disclosures; disclosures for other authors are detailed in the paper.

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