STICH

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Velazquez EJ, et al. "Coronary-Artery Bypass Surgery in Patients with Left Ventricular Dysfunction". The New England Journal of Medicine. 2011. 354(17):1607-1616.
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Clinical Question

Among patients with ischemic cardiomyopathy with LVEF ≤35%, does OMT plus CABG improve mortality compared to OMT alone?

Bottom Line

Among patients with ischemic cardiomyopathy with LVEF ≤35%, the addition of CABG to OMT does not significantly reduce all-cause mortality after 5 years but does reduce CV-related deaths and hospitalizations. After 10 years, there is a significant reduction in all-cause mortality with CABG.

Major Points

The CASS trial (1985) demonstrated no overall survival benefit with CABG compared to OMT among patients with stable CAD. However, survival was improved in a subset of patients with systolic dysfunction and 3-vessel coronary disease. Optimal therapy for patients with severe CAD and LV dysfunction had not been formally addressed in larger randomized trials, and data among patients with more severe LV dysfunction (LVEF ≤35%) had been limited.

Hypothesis one of the Surgical Treatment for Ischemic Heart Failure (STICH) trial randomized 1,212 patients with LVEF ≤35% and stable CAD eligible for CABG to either OMT plus CABG or OMT alone. Coronary angiography excluded patients with ACS or critical left main coronary disease. At a mean follow-up of 4.7 years, there was no difference in the primary outcome of all-cause mortality, although OMT plus CABG was associated with fewer CV-related deaths and hospitalizations than OMT alone. Follow-up data at 10 years, published in 2016, showed a significant reduction in all-cause mortality with CABG+OMT compared to OMT alone (58.9% vs 66.1%, p=0.02 [CI 0.73-0.97]).[1] STICH hypothesis 2 (2009) also showed no reduction in the rate of CV-related death hospitalizations with the addition of surgical ventricular reconstruction (SVR) to CABG.[2]

Guidelines

AHA/ACCF Heart Failure (2013, adapted)[3]

  • CABG or PCI indicated for HFpEF or HFrEF on OMT with angina and suitable coronary artery, for example L main stenosis >50% or L main equivalent (class I, level C)
  • CABG for survival benefit is reasonable if LVEF 35-50% and ≥70% stenosis multivessel CAD or proximal LAD stenosis if viable myocardium is in revascularization area (class IIa, level B)
  • CABG or medical therapy if LVEF <35% and significant CAD (class IIa, level B)
  • CABG can be considered for survival benefit if LVEF <35% and operable coronary anatomy regardless of presence of viable myocardium (class IIb, level B)

Design

  • Multicenter, non-blinded, parallel group, randomized controlled trial
  • N=1,212 patients with ischemic cardiomyopathy
    • OMT plus CABG (n=610)
    • OMT alone (n=602)
  • Setting: 99 centers in 22 countries
  • Enrollment: 2002-2007
  • Mean follow-up: 4.7 years
  • Analysis: Intention-to-treat
  • Primary outcome: All-cause mortality

Population

Inclusion Criteria

  • Age ≥18 years
  • CAD suitable for revascularization
  • LVEF ≤35%

Exclusion Criteria

  • Critical LM disease or ACS
  • Recent MI causing LV dysfunction; or cardiogenic shock in previous 72 hours
  • History of previous CABG or planned PCI
  • Aortic valvular disease requiring repair or replacement
  • High risk for operative mortality
  • Previous heart, kidney, liver, or lung transplantation
  • Life expectancy <3 years due to non-cardiac illness
  • Poor medical adherence
  • Childbearing potential

Baseline Characteristics

  • Demographics: Age 60 years, male 88%, White race 66%,
  • Health data: BMI 27 kg/m2, SBP 120 mmHg, pulse 74 bpm
  • Median 6MWT: 1145 feet
  • PMH/PSH: MI 77%, PCI 13%, CABG 3%, HTN 60%, HLD 60%, DM 39%, CKD 8%, CVA 8%, current smoker 21%
  • CCS angina class:
    • 0: 37%
    • I: 15%
    • II: 43%
    • III: 4%
    • IV: 1%
  • NYHA class:
    • I: 12%
    • II: 51%
    • III: 34%
    • IV: 3%
  • Medications: Aspirin 83%, clopidogrel 17%, ACE inhibitors 82%, ARB 9%, beta-blocker 85%, statin 81%, nitrate 53%, loop diuretic 66%, potassium-sparing diuretic 75%, digoxin 20%

Interventions

  • Randomized to CABG plus OMT or OMT alone
  • Follow-up at discharge or 30 days, every 4 months for 1 year, then every 6 months thereafter
  • CABG plus OMT arm: 91% underwent CABG with median time to surgery of 10 days
  • OMT only arm: 17% underwent CABG with median time of 142 days

Outcomes

Comparisons are OMT plus CABG vs. OMT.

Primary Outcomes

All-cause mortality
36% vs. 41% (HR 0.86; 95% CI 0.72-1.04; P=0.12)
Per-protocol: 34% vs. 42.6% (HR 0.76; 95% CI 0.62-0.92; P=0.005)
Per-treatment: 33% vs. 44% (HR 0.70; 95% CI 0.58-0.84; P<0.001)

Secondary Outcomes

CV death
28% vs. 33% (HR 0.81; 95% CI 0.66-1.00; P=0.05)
All-cause mortality or CV hospitalization
58% vs. 68% (HR 0.74; 95% CI 0.64-0.85; P<0.001)
All-cause mortality within 30 days of randomization
4% vs. 1% (HR 3.12; 95% CI 1.33-7.31; P=0.006)
All-cause mortality or HF hospitalizations
48% vs. 54% (HR 0.84; 95% CI 0.71-0.98; P=0.03)
All-cause mortality or hospitalizations
65% vs. 73% (HR 0.81; 95% CI 0.71-0.93; P=0.003)
All-cause mortality or revascularization with CABG or PCI
39% vs. 55% (HR 0.60; 95% CI 0.51-0.71; P<0.001)

Subgroup Analysis

No significant interactions between treatment assignment and baseline characteristics with respect to primary outcome.

Criticisms

  • Identified by the authors:
    • Limited power and duration to detect a benefit of CABG
    • Lack of blinding likely altered the non-fatal outcomes
  • Identified in letters to the editor:[4]
    • Slow enrollment (2.5 participants per site per year) reduces generalizability and external validity
    • Authors' claim that mortality isn't detectable because of lack of power is likely inaccurate as the rate of death was higher than in their power calculation
    • Risk of death incurred from the CABG procedure itself may have been mitigated by pursuing PCI
    • Given the rates of death in this trial, a larger trial with at least 1,300 participants in each group is likely needed with the high rate of expected crossover
    • Use of ICDs was low and does not meet that of current guidelines
    • Age of those in this trial was significantly lower than those routinely undergoing CABG
  • Identified elsewhere:
    • Significant crossover (17%) was lower than prespecified 20%, but makes it more difficult to demonstrate benefit to CABG in intention-to-treat analysis[5]

Funding

  • National Heart, Lung, and Blood Institute
  • Abbott Laboratories
  • Authors with multiple conflicts

Further Reading

  1. Subherwal S et al. Temporal trends in and factors associated with bleeding complications among patients undergoing percutaneous coronary intervention: a report from the National Cardiovascular Data CathPCI Registry. J. Am. Coll. Cardiol. 2012. 59:1861-9.
  2. Jones RH et al. Coronary bypass surgery with or without surgical ventricular reconstruction. N. Engl. J. Med. 2009. 360:1705-17.
  3. Yancy CW, et al. "2013 ACCF/AHA guideline for the management of heart failure." Circulation. 2013;128:e240-e327.
  4. Letters to the editor
  5. Fang JC. "Underestimating Medical Therapy for Coronary Disease...Again" N Engl J Med 2011; 364:1671-1673