Clinical Investigation
Effect of carvedilol vs metoprolol succinate on mortality in heart failure with reduced ejection fraction

https://doi.org/10.1016/j.ahj.2018.01.005Get rights and content

Abstract

Background

Beta blocker therapy is indicated in all patients with heart failure with reduced ejection fraction (HFrEF) as per current guidelines. The relative benefit of carvedilol to metoprolol succinate remains unknown. This study aimed to compare survival benefit of carvedilol to metoprolol succinate.

Methods

The VA’s databases were queried to identify 114,745 patients diagnosed with HFrEF from 2007 to 2015 who were prescribed carvedilol and metoprolol succinate. The study estimated the survival probability and hazard ratio by comparing the carvedilol and metoprolol patients using propensity score matching with replacement techniques on observed covariates. Sub-group analyses were performed separately for men, women, elderly, duration of therapy of more than 3 months, and diabetic patients.

Results

A total of 43,941 metoprolol patients were matched with as many carvedilol patients. The adjusted hazard ratio of mortality for metoprolol succinate compared to carvedilol was 1.069 (95% CI: 1.046-1.092, P value: < .001). At six years, the survival probability was higher in the carvedilol group compared to the metoprolol succinate group (55.6% vs 49.2%, P value < .001). The sub-group analyses show that the results hold true separately for male, over or under 65 years old, therapy duration more than three months and non-diabetic patients.

Conclusion

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.

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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    From: Krannert Institute of Cardiology, Indiana University School of Medicine and Roudebush VA Medical Center, Indianapolis IN 46202.

    Funding: None.

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