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Published on: June 10, 2025
Incremental Reduction in Risk of Death Associated With Use of Guideline-Recommended Therapies in Patients With Heart
Gregg C Fonarow1, Nancy M Albert, Anne B Curtis
1Ahmanson-UCLA Cardiomyopathy Center, Ronald Reagan UCLA Medical Center, Los Angeles, CA (G.C.F.).
Insights
Guideline-recommended heart failure therapies improve survival in patients with reduced ejection fraction. Combining 4-5 therapies offers significant survival benefits, with a potential plateau effect.
Area of Science:
- Cardiology
- Heart Failure Research
- Clinical Effectiveness Studies
Background:
- Guideline-recommended therapies exist to reduce mortality in heart failure (HF) with reduced left ventricular ejection fraction (HFrEF).
- The incremental clinical effectiveness of combining these HF therapies has not been well studied.
- Evaluating individual and combined benefits is crucial for optimizing patient outcomes.
Purpose of the Study:
- To evaluate the individual and incremental benefits of guideline-recommended HF therapies on 24-month survival.
- To identify which therapies provide the greatest survival advantage in HFrEF patients.
- To determine the optimal number of therapies for maximizing survival benefits.
Main Methods:
- A nested case-control study was conducted using data from the IMPROVE HF registry.
- Cases were patients who died within 24 months; controls were propensity-matched survivors (1:2 ratio).
- Logistic regression analyzed the association between therapies and survival, calculating attributable mortality risk.
Main Results:
- Beta-blockers and cardiac resynchronization therapy showed the greatest 24-month survival benefit.
- Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ICDs, anticoagulation for AF, and HF education also provided survival benefits.
- Aldosterone antagonists did not show a significant survival benefit; incremental benefits plateaued at 4-5 therapies.
Conclusions:
- Individual and combined use of most guideline-recommended therapies significantly improves survival in HFrEF.
- A potential plateau in survival benefit is observed when 4 to 5 therapies are implemented.
- These findings support the comprehensive application of guideline-recommended therapies for HFrEF patients without contraindications.
Background:
Several therapies are guideline-recommended to reduce mortality in patients with heart failure (HF) and reduced left ventricular ejection fraction, but the incremental clinical effectiveness of these therapies has not been well studied. We aimed to evaluate the individual and incremental benefits of guideline-recommended HF therapies associated with 24-month survival.
Methods And Results:
We performed a nested case-control study of HF patients enrolled in IMPROVE HF. Cases were patients who died within 24 months and controls were patients who survived to 24 months, propensity-matched 1:2 for multiple prognostic variables. Logistic regression was performed, and the attributable mortality risk from incomplete application of each evidence-based therapy among eligible patients was calculated. A total of 1376 cases and 2752 matched controls were identified. β-Blocker and cardiac resynchronization therapy were associated with the greatest 24-month survival benefit (adjusted odds ratio for death 0.42, 95% confidence interval (CI), 0.34-0.52; and 0.44, 95% CI, 0.29-0.67, respectively). Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, implantable cardioverter-defibrillators, anticoagulation for atrial fibrillation, and HF education were also associated with benefit, whereas aldosterone antagonist use was not. Incremental benefits were observed with each successive therapy, plateauing once any 4 to 5 therapies were provided (adjusted odds ratio 0.31, 95% CI, 0.23-0.42 for 5 or more versus 0/1, P<0.0001).
Conclusions:
Individual, with a single exception, and incremental use of guideline-recommended therapies was associated with survival benefit, with a potential plateau at 4 to 5 therapies. These data provide further rationale to implement guideline-recommended HF therapies in the absence of contraindications to patients with HF and reduced left ventricular ejection fraction. (J Am Heart Assoc. 2012;1:16-26.).
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