STICH: CABG for Ischemic Heart Failure (2011)
“In a cohort of patients with coronary artery disease and left ventricular dysfunction, there was no significant difference in the rate of death from any cause between patients who underwent medical therapy alone and those who underwent medical therapy plus CABG.”
— The STICH Investigators
1. Publication Details
- Trial Title: Coronary-Artery Bypass Surgery in Patients with Ischemic Cardiomyopathy.
- Citation: Velazquez EJ, Lee KL, Deja MA, et al; for the STICH Investigators. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364(17):1607-1616. doi:10.1056/NEJMoa1100356.
- Published: April 28, 2011, in The New England Journal of Medicine.
- Author: Eric J. Velazquez, M.D.
- Funding: National Heart, Lung, and Blood Institute (NHLBI).
2. Keywords
Ischemic Cardiomyopathy, Heart Failure, Coronary Artery Bypass Grafting (CABG), Medical Therapy, Left Ventricular Dysfunction, Coronary Artery Disease.
3. The Clinical Question
In patients with coronary artery disease and severe left ventricular systolic dysfunction (ejection fraction ≤35%) (Population), does coronary artery bypass grafting (CABG) plus optimal medical therapy (Intervention) compared to optimal medical therapy alone (Comparison) reduce the rate of all-cause mortality (Outcome)?
4. Background and Rationale
- Existing Knowledge: Ischemic heart disease is a leading cause of heart failure. While CABG was known to improve survival in patients with coronary artery disease and preserved or moderately impaired LV function, its role in patients with severe LV dysfunction was uncertain.
- Knowledge Gap: It was unknown whether the high operative risks of CABG in patients with severe heart failure were justified by a potential long-term survival benefit. The benefit of revascularizing dysfunctional but viable myocardium in this population had not been established in a large randomized trial.
- Proposed Hypothesis: The authors hypothesized that CABG, when added to optimal medical therapy, would reduce the rate of death from any cause as compared with medical therapy alone.
5. Study Design and Methods
- Design: A prospective, multicenter, international, randomized, unblinded, controlled trial.
- Setting: 99 clinical centers in 22 countries.
- Trial Period: Enrollment from July 2002 to May 2007.
- Population:
- Inclusion Criteria: Patients with an ejection fraction of ≤35% and coronary artery disease amenable to CABG.
- Exclusion Criteria: Recent myocardial infarction, cardiogenic shock, or left main coronary artery stenosis >50%.
- Intervention: Optimal medical therapy plus CABG.
- Control: Optimal medical therapy alone.
- Management Common to Both Groups: Both groups received guideline-directed optimal medical therapy for heart failure, including ACE inhibitors/ARBs, beta-blockers, and aldosterone antagonists as appropriate.
- Power and Sample Size: The trial was powered to detect a 22% relative reduction in the risk of death, requiring 1200 patients.
- Outcomes:
- Primary Outcome: All-cause mortality.
- Secondary Outcomes: Included death from cardiovascular causes, and death from any cause or hospitalization for cardiovascular causes.
6. Key Results
- Enrollment and Baseline: 1212 patients were randomized (610 to CABG plus medical therapy, 602 to medical therapy alone). The groups were well-matched at baseline.
- Trial Status: The trial was completed as planned, with a median follow-up of 56 months.
- Primary Outcome: There was no significant difference in the primary outcome of all-cause mortality between the CABG and medical therapy alone groups (36% vs 41%; P=0.12).
- Secondary Outcomes: The CABG group had significantly lower rates of death from cardiovascular causes and of the composite of death from any cause or hospitalization for cardiovascular causes.
- Adverse Events: Patients in the CABG group had a higher risk of perioperative complications, including a higher rate of stroke within 30 days.
7. Medical Statistics
- Analysis Principle: An intention-to-treat analysis was performed.
- Statistical Tests Used: The primary outcome was analyzed using the log-rank test.
- Primary Outcome Analysis: Time to death from any cause was compared between the two groups using a Kaplan-Meier analysis.
- Key Statistic(s) Reported: Hazard Ratio (HR) for all-cause mortality with CABG: 0.86 (95% CI, 0.72 to 1.04; P=0.12).
- Interpretation of Key Statistic(s):
- Hazard Ratio (HR): An HR of 0.86 suggests a 14% lower hazard of death with CABG, but this did not reach statistical significance.
- Confidence Interval (CI): The 95% CI crosses 1.0, confirming the lack of a statistically significant difference for the primary outcome.
- P-value: The p-value of 0.12 is above the 0.05 threshold.
- Clinical Impact Measures: Not applicable for the primary outcome as no significant difference was shown.
- Subgroup Analyses: No significant interactions were found in pre-specified subgroup analyses.
8. Strengths of the Study
- Study Design and Conduct: This was a large, international, multicenter, randomized trial that addressed a fundamental and long-standing question in cardiology.
- Generalizability: The inclusion of 99 centers worldwide increases the applicability of the findings.
- Long-term Follow-up: The nearly 5-year median follow-up was a major strength, allowing for the assessment of long-term outcomes.
9. Limitations and Weaknesses
- Internal Validity (Bias): The study was unblinded. A significant number of patients (17%) in the medical therapy group crossed over to receive CABG during follow-up.
- External Validity (Generalizability): The medical therapy available for heart failure has continued to evolve since the trial was conducted (e.g., with the introduction of ARNIs and SGLT2 inhibitors).
- Other: The primary outcome was not met, and the benefit was seen in secondary endpoints. The event rates were lower than anticipated, which may have underpowered the study for its primary endpoint.
10. Conclusion of the Authors
“In this randomized trial, there was no significant difference between medical therapy alone and medical therapy plus CABG with respect to the primary end point of death from any cause. Patients assigned to CABG, as compared with those assigned to medical therapy alone, had lower rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes.”
11. To Summarize
- Impact on Current Practice: The STICH trial was highly influential. Despite the neutral primary outcome, the significant benefits seen in key cardiovascular secondary endpoints, combined with subsequent long-term follow-up showing a mortality benefit emerging over time, solidified the role of CABG as an important therapeutic option for appropriately selected patients with ischemic cardiomyopathy.
- Specific Recommendations:
- Patient Selection: For patients with severe ischemic LV dysfunction (EF ≤35%) and significant coronary artery disease.
- Actionable Intervention: CABG should be considered in addition to optimal medical therapy to reduce cardiovascular death and hospitalization.
- Expected Benefit: No proven all-cause mortality benefit at 5 years, but a significant reduction in cardiovascular death and hospitalization.
- What This Trial Does NOT Mean: This trial does not mean all patients with ischemic cardiomyopathy should undergo CABG. The decision requires careful consideration of operative risk, coronary anatomy, and patient comorbidities.
- Implementation Caveats: The benefits of CABG must be weighed against the upfront risks of major surgery.
12. Context and Related Studies
- Building on Previous Evidence: STICH was the definitive trial that provided randomized evidence to guide a practice that was previously based on observational data and clinical judgment.
- Influence on Subsequent Research: The long-term (10-year) follow-up of the STICHES trial (2016) was crucial, as it ultimately did show a significant reduction in all-cause mortality with CABG, confirming that the benefit of surgery accrues over time. This has cemented the recommendations in clinical guidelines.
13. Unresolved Questions & Future Directions
- Unresolved Questions: What is the role of percutaneous revascularization (PCI) compared to CABG in this high-risk population? How do newer medical therapies for heart failure modify the relative benefit of revascularization?
- Future Directions: Future research is needed to compare surgical versus percutaneous revascularization in this population and to integrate the findings of STICH with the modern era of heart failure pharmacotherapy.
14. External Links
15. Framework for Critical Appraisal
- Clinical Question: The question was of fundamental importance, addressing a major treatment decision for a large and high-risk patient population.
- Methods: The large, multicenter, randomized design was appropriate. The main limitations were the open-label design and the significant crossover rate from the medical therapy arm.
- Results: This is a classic example of a trial where the primary endpoint was neutral, but strong signals of benefit in important secondary endpoints and subsequent long-term follow-up were ultimately practice-changing. The separation of the Kaplan-Meier curves over time was a key finding.
- Conclusions and Applicability: The authors’ conclusion is a precise reflection of the initial 5-year data. However, the long-term STICHES results are now integral to the interpretation of the trial. The findings are highly applicable and form the evidentiary basis for recommending CABG in selected patients with ischemic cardiomyopathy.
16. Disclaimer and Contact
This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.