CardioExchange Archive

CardioExchange welcomes Eric J. Velazquez, an investigator for the STICH (Surgical Treatment for Ischemic Heart Failure) trial, results of which were recently published in two articles in the New England Journal of Medicine. Dr. Velazquez is the lead author of the STICH article that focuses on the clinical value of coronary artery bypass grafting (CABG) in patients with left-ventricular dysfunction. Dr. Velazquez answers questions about the trial from CardioExchange’s Dr. Anju Nohria. We welcome you to offer your own questions and opinions.

Background: In the STICH trial, 1212 patients with an LV ejection fraction ≤35% and coronary artery disease amenable to CABG were randomized to undergo either medical therapy alone or medical therapy plus CABG. According to an intention-to-treat analysis, the primary outcome of all-cause mortality (median follow-up, 56 months) was nonsignificantly lower in the group that underwent CABG than in the group that did not (36% vs. 41%; P=0.12). However, the advantage of CABG did reach statistical significance with respect to the rate of death from an adjudicated cardiovascular cause (28% vs. 33%; P=0.05) and death from any cause or hospitalization for a cardiovascular cause (58% vs. 68%; P<0.001).

In a substudy of 601 STICH participants, viability of myocardium was assessed with single-photo-emission computed tomography (SPECT), dobutamine echocardiography, or both. The mortality rate was significantly lower among patients with viable myocardium than among those without viable myocardium (37% vs. 51%; P=0.003), although that difference became nonsignificant after adjustment for other baseline variables (P=0.21). For mortality, no interaction was found between myocardium-viability status and either CABG or medical therapy.

Dr. Nohria: As you note in your discussion, the intention-to-treat analysis did not show an all-cause mortality difference between the two groups, but the per-treatment analysis showed an advantage of medical therapy plus CABG. You acknowledge that the imbalance in the crossover rates between the 2 groups may have diminished the evidence of efficacy from CABG in the intention-to-treat analysis. Given that, do you consider STICH a negative trial?

Dr. Velazquez: No trial is “negative” if patients and physicians win by having access to truly new data to inform complex decision making. The totality of the information — i.e., the adjusted analyses of the as-randomized (intention-to-treat population) for the all-cause mortality endpoint, the unadjusted and adjusted analyses of the important secondary endpoints, and the treatment-received and per-protocol analyses of all the endpoints — clearly supports the clinical efficacy of CABG plus medical therapy over that of medical therapy alone. My fellow investigators and I hypothesized that CABG plus medical therapy would reduce unadjusted all-cause mortality by 25%; instead, the hazard ratio in the CABG group was 0.86 (relative risk reduction, 14%; P=0.12). So from a purely statistical perspective, our finding did not prove our hypothesis; what we may infer clinically from the data is a different thing.

Nohria: How do the STICH findings influence your own clinical decision making about medical therapy versus CABG in patients with coronary artery disease and LV dysfunction?

Velazquez: This is in many ways the perfect finding for clinicians: It is nuanced, but so is clinical care and life. The STICH results reinforce for me the absolutely critical need for all of us as clinicians to spend time talking to one another and, more important, to patients, so that we can better understand their wishes and inform them about the risks and benefits of treatment choices. Neither medical therapy alone nor CABG is a magic pill or procedure. Medical therapy is effective, but with a 40% mortality rate at 5 years, it is not a cure and requires frequent reassessment. Patients and physicians do not need to rush the decision for CABG. If after careful review, however, there is a decision to take an up-front risk, I believe there will be a modest but clinically meaningful chance of improving long-term survival.

Nohria: Patients in the CABG group had a higher all-cause mortality rate in the first 2 years, particularly in the first 30 days, compared with patients who received medical therapy alone. In the STICH database, did you identify any patient characteristics (e.g., LV end-diastolic diameter, renal function, etc.) that predict a greater likelihood of early mortality after surgery?

Velazquez: Great question. Stay tuned, as much more is to come as we analyze what is a superbly rich database.

Nohria: Do you believe that myocardial viability testing has little value in helping clinicians decide who might benefit from surgery? Or do you think that other modalities such as PET or MRI may be more helpful than SPECT and dobutamine echo?

Velazquez: These data tell me that viability testing, regardless of the results, should not exclude patients from CABG. In fact, the data point to an early suggestion that the patients who may benefit the most from CABG are those without myocardial viability, turning the paradigm on its head. I have always said that functional recovery (of LV ejection fraction) does not necessarily equate with improved outcomes, no matter how much we wish it were so. We have seen that for decades with medical-therapy trials, going back to V-HeFT II. Regarding modality of testing, to alter the interpretation of the results, cardiac MRI and PET would have to be dramatically more sensitive for viability, and the results of that increased sensitivity would need to be completely independent of other more easily measurable and readily available clinical and imaging data. That has never been shown to be the case for clinical (not functional) outcomes.

Nohria: What percentage of patients in each treatment arm had cardiac resynchronization therapy defibrillators (CRT-Ds) or implantable cardioverter-defibrillators (ICDs)?

Velazquez: The initial percentage of patients with ICDs was about 2% in each arm; that eventually rose to 19% in the medical therapy arm and 14% in the CABG arm. CRT-D use was 5% by the end of the trial. The slight imbalance in ICD use may have biased the results against CABG, but we have not analyzed that carefully yet.

Nohria: To assess whether CABG resulted in positive remodeling, did you analyze any follow-up LV ejection fraction or LVEDD data before and after surgery?

Velazquez: Stay tuned.

For more of our ACC.11 coverage of late-breaking clinical trials, interviews with the authors of the most important research, and blogs from our fellows on the most interesting presentations at the meeting, check out our Coverage Roundup.