Clinical InvestigationEffect of carvedilol vs metoprolol succinate on mortality in heart failure with reduced ejection fraction
Section snippets
Background
Beta blocker therapy is indicated in the treatment of all patients with heart failure with reduced ejection fraction (HFrEF) as per current guidelines1., 2., 3.. Overexpression of beta-1 and beta-24 leads to cardiomyopathy and increased fibrosis and cardiomyocyte apoptosis suggesting their role in heart failure.5 Catecholamines trigger alpha-1 and beta-2 receptors, causing vasoconstriction and vasodilatation, with vasodilation being impaired in heart failure.6., 7., 8. The three trial-proven
Study population
The Veteran’s Affairs (VA) administration provides care for approximately 9 million veterans and their families in the United States.14 Patients with HFrEF were identified using International Classification of Diseases 9th Revision (ICD-9) codes. During the period of analysis carvedilol and metoprolol succinate were restricted by the VA pharmacy exclusively for patients with a diagnosis of HF with an ejection fraction less than 40% in the VA system. Pharmacy consultation is required for a
Results
The original query contained 881,804 veterans, and 165,159 veterans with diagnosis of HFrEF remained after the removal of patients without continuous carvedilol or metoprolol succinate use. After removing veterans with missing information on baseline characteristics or outcomes, the study group was comprised of 114,745 HF patients treated with either carvedilol (61.71%) or metoprolol succinate (38.29%). Before matching, the average follow-up time was 3.46±0.02 years for carvedilol group and
Discussion
To our knowledge, this is the largest study comparing carvedilol to metoprolol succinate for mortality in patients with HFrEF and includes contemporary patients in a setting outside of the confines of a randomized trial. The study demonstrated that overall, carvedilol use is associated with lower all-cause mortality compared to metoprolol succinate when matched for comorbidities. For the entire matched sample, the mortality rate of metoprolol was 43.1%, whereas the mortality rate of carvedilol
Conclusion
Our study demonstrated that overall patients with HFrEF taking carvedilol had improved survival as compared to metoprolol succinate. The data supports the need for furthering testing to determine optimal choice of beta blockers in patients with heart failure with reduced ejection fraction.
Acknowledgements
This material is the result of work supported with resources and the use of facilities at the Richard L. Roudebush VA Medical Center.
The contents of this study do not represent the views of the U.S. Department of Veterans Affairs or United States Government.
Funding
No funding was received.
Disclosures
No conflicts of interests to disclose for all authors.
Clinical perspectives
This study demonstrates an important question for patient care, because there are multiple beta blockers available to treat heart failure. Our data suggest that carvedilol may be considered as first-line therapy in clinical decision making.
Translational outlook
These data support the need for definitive randomized controlled trial examining outcomes and response between carvedilol and metoprolol succinate.
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Expert consensus statement on heart failure with reduced ejection fraction: beyond the guidelines
2020, Revista Espanola de Cardiologia SuplementosEffect on Mortality of Higher Versus Lower β-Blocker (Metoprolol Succinate or Carvedilol) Dose in Patients With Heart Failure
2018, American Journal of CardiologyCitation Excerpt :They remained consistent for metoprolol succinate (HR 0.88, 95% CI 0.85 to 0.91, p <0.01) and carvedilol (HR 0.65, 95% CI 0.63 to 0.67, p <0.01) with average daily dose of 103 mg and 18 mg, respectively. The improved survival of carvedilol over metoprolol succinate is consistent to our previous study.8 From the treatment effects model, we find that the estimated average time to mortality when all matched sample were treated using low dose was 6.6.
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From: Krannert Institute of Cardiology, Indiana University School of Medicine and Roudebush VA Medical Center, Indianapolis IN 46202.
Funding: None.