Review of the STICH trial

Coronary-Artery Bypass Surgery in Patients with Left Ventricular Dysfunction

N Engl J Med 2011;364:1607-1616

Background: The three pivotal trials of coronary artery bypass graft surgery (CABG) we previously reviewed, largely included patients with normal left ventricular function. Observational studies suggested that CABG improved survival over medical therapy in patients with coronary artery disease and systolic heart failure.

The Surgical Treatment for Ischemic Heart Failure (STICH) trial sought to test the hypothesis that CABG reduces mortality in patients with coronary artery disease and left ventricular systolic dysfunction.

Of note, the STICH had two hypotheses: medical therapy vs CABG (hypothesis 1) or CABG vs CABG plus surgical ventricular reconstruction (hypothesis 2) “patients in all arms received medical therapy according to the guidelines at that time”. In this review we focus on hypothesis 1. We are also reporting the 5-year results of STICH since that was the primary intended follow up time.

Patients: Eligible patients had coronary artery disease that was amenable to surgery and left ventricular ejection fraction of 35% or less. Patients were excluded if they had recent myocardial infarction, cardiogenic shock within 72 hours of randomization, life expectancy <3 years due to non-cardiac illness, poor treatment adherence, or 50% or more left main disease.

Baseline characteristics: The study enrolled 1212 patients – 602 assigned to medical therapy alone and 610 assigned to medical therapy plus CABG. The average age of patients was 60 years with 88% being men. The median body mass index was 27 kg/m2. Approximately 77% had prior myocardial infarction, 60% had hyperlipidemia, 60% had hypertension, 39% had diabetes, 8% had chronic kidney disease, 8% had prior stroke and 21% were active smokers. Approximately 3% had previous CABG.

NYHA class was II in 52% of the patients and III in 34%. Approximately 30% of the patients had two vessel disease and 60% had three vessel disease. Left main stenosis (50% or more) was present in 3% of the patients and left anterior descending artery stenosis (75% or more) was present in 68%.

Medications at baseline were as follows: beta-blockers in 85%, ACEi or ARB in 90%, potassium-sparing diuretic in 46%, aspirin in 83% and statins in 81%.

Procedures: Patients were randomly assigned to receive medical therapy alone or medical therapy plus CABG. Guideline-based medical treatment and devices were recommended by a lead cardiologist at each center. The surgeries were performed by surgeons who provided data on at least 25 patients with an ejection fraction of 40% or less, in whom they performed CABG, and had an operative mortality of 5% or less.

CABG was to be performed within 14 days after randomization. Patients were followed up at the time of discharge or at 30 days, every 4 months for the first year then every 6 months thereafter.

Endpoints: The primary end point was all-cause death. Secondary endpoints included death from cardiovascular causes and death from any cause or hospitalization for cardiovascular causes.

Statistical analysis was performed based on the intention-to-treat principle. The original sample size was 2,000 patients to be followed for 3 years. Assuming a 3-year mortality of 25% in the medical arm, this would give the study 90% power to detect 25% mortality reduction with CABG. Due to slow enrollment, the sample size was reduced to 1,200 patients and the follow up time was increased to 5 years.

Results: The median follow up time was 56 months. Among the patients assigned to surgery, 555 (91%) underwent CABG, of whom 91% received at least one arterial conduit. Among the patients assigned to the medical arm, 100 (17%) underwent CABG.

CABG did not reduce mortality compared to medical therapy alone (36% with CABG vs 41% with medical therapy, HR, 0.86, 95% CI: 0.72 - 1.04; p=0.12). CABG reduced cardiovascular death (28% vs 33%, HR: 0.81, 95% CI 0.66 - 1.00; p=0.05) and the composite secondary endpoint of death from any cause or hospitalization for cardiovascular causes (58% vs 68%, HR: 0.74, 95% CI: 0.64 - 0.85; p<0.001).

There were no significant subgroup interactions based on baseline characteristics. The hazard ratio with CABG for selected high risk subgroups is as follows: 0.93 for age 65 or above, 0.80 for younger than 65, 0.92 for patients with diabetes, 0.83 for patients without diabetes, 0.79 for 3-vessel disease and 0.82 for left main or left anterior descending artery disease. The hazard ratio for patients without left main or left anterior descending artery disease was 0.97. Hazard ratio was 0.75 for women and 0.87 for men. P for interaction was > 0.20 for the above groups.

Conclusion: In patients with coronary artery disease and left ventricular ejection fraction of 35% or less, CABG did not improve survival compared to medical therapy alone, over 5 years follow up.

This was an important trial since medical therapy and surgical techniques improved significantly since the publication of the three pivotal trials that were published in the 1970s and 1980s. It’s important to appreciate that this trial included a high-risk group; over one third were dead at 5 years. In comparison, the mortality rate in the Coronary Artery Bypass Graft Surgery Trialists Collaboration was 30.5% in the medical arm at 10-years follow up.

An important limitation of the trial is the lack of details regarding the number of patients screened to enrolled, along with the reasons for slow enrollment or characteristics of excluded patients. This makes it difficult for physicians to determine the proportion of their patients who would have been eligible for the trial.