Meta-Analysis
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Feb 26, 2017; 9(2): 182-190
Published online Feb 26, 2017. doi: 10.4330/wjc.v9.i2.182
Ivabradine in the treatment of systolic heart failure - A systematic review and meta-analysis
Mahesh Anantha Narayanan, Yogesh N V Reddy, Janani Baskaran, Abhishek Deshmukh, David G Benditt, Ganesh Raveendran
Mahesh Anantha Narayanan, Janani Baskaran, David G Benditt, Ganesh Raveendran, Division of Cardiovascular Diseases, University of Minnesota Medical Center, Minneapolis, MN 55455, United States
Yogesh N V Reddy, Abhishek Deshmukh, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, United States
Author contributions: All authors contributed to this manuscript.
Conflict-of-interest statement: Drs. Mahesh Anantha Narayanan, Yogesh N Reddy, Janani Baskaran and Ganesh Raveendran have no disclosures; Dr. Benditt is a consultant for and holds equity in Medtronic Inc., and St Jude Medical Inc. Dr. Benditt is supported in part by a grant from the Dr. Earl E Bakken Family in support of heart-brain research.
Data sharing statement: Since this is a meta-analysis and data was generated from previous published papers, data is not available for sharing beyond that contained within the report.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Mahesh Anantha Narayanan, MD, Division of Cardiovascular Diseases, University of Minnesota Medical Center, 500 SE Harvard Street, Minneapolis, MN 55455, United States. manantha@umn.edu
Telephone: +1-507-3192446 Fax: +1-612-6264411
Received: November 1, 2016
Peer-review started: November 4, 2016
First decision: December 15, 2016
Revised: January 7, 2017
Accepted: January 16, 2017
Article in press: January 18, 2017
Published online: February 26, 2017
Abstract
AIM

To perform a systematic-review and meta-analysis to compare outcomes of ivabradine combined with beta-blocker to beta-blocker alone in heart failure with reduced ejection fraction (HFrEF).

METHODS

We searched PubMed, Cochrane, EMBASE, CINAHL and Web of Science for trials comparing ivabradine + beta-blocker to beta-blocker alone in HFrEF. We performed a systematic-review and meta-analysis of published literature. Primary end-point was combined end point of cardiac death and hospitalization for heart failure.

RESULTS

Six studies with 17671 patients were included. Mean follow-up was 8.7 ± 7.9 mo. Combined end-point of heart failure readmission and cardiovascular death was better in ivabradine + beta-blocker group compared to beta-blocker alone (RR: 0.93, 95%CI: 0.79-1.09, P = 0.354). Mean difference (MD) in heart rate was higher in the ivabradine + beta-blocker group (MD: 6.14, 95%CI: 3.80-8.48, P < 0.001). There was no difference in all cause mortality (RR: 0.98, 95%CI: 0.89-1.07, P = 0.609), cardiovascular mortality (RR: 0.99, 95%CI: 0.86-1.15, P = 0.908) or heart failure hospitalization (RR: 0.87, 95%CI: 0.68-1.11, P = 0.271).

CONCLUSION

From the available clinical trials, ivabradine + beta-blocker resulted in a significantly greater reduction in HR coupled with improvement in combined end-point of heart failure readmission and cardiovascular death but with no improvement in all cause or cardiovascular mortality. Given the limited evidence, further randomized controlled trials are essential before widespread clinical application of ivabradine + beta-blocker is advocated for HFrEF.

Keywords: Ivabradine, Heart failure

Core tip: Ivabradine was recently given a class IIa indication in the 2016 focused update on systolic heart failure in the ACC/AHA/HFSA guidelines. But it is unclear whether ivabradine offers any additional benefit over and above that offered by beta blockers. Our analysis showed lower heart rate and combined end point of cardiac death and heart failure hospitalization at follow-up with ivabradine combined with beta blocker compared to beta blocker alone. Combined therapy did not improve cardiovascular mortality, all cause mortality or heart failure hospitalization. Further studies are essential before widespread use of combination therapy with ivabradine can be recommended.