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. 2017 Feb 26;9(2):182-190.
doi: 10.4330/wjc.v9.i2.182.

Ivabradine in the treatment of systolic heart failure - A systematic review and meta-analysis

Mahesh Anantha Narayanan  1 , Yogesh N V Reddy  1 , Janani Baskaran  1 , Abhishek Deshmukh  1 , David G Benditt  1 , Ganesh Raveendran  1
Affiliations

Ivabradine in the treatment of systolic heart failure - A systematic review and meta-analysis

Mahesh Anantha Narayanan et al. World J Cardiol. .

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: Heart failure; Ivabradine.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Comparison of Mantel-Haenszel risk ratio for combined end points of cardiovascular death and hospitalization for heart failure between ivabradine + beta-blocker vs beta-blocker alone. MH RR: Mantel-Haenszel risk ratio; BB: Beta blockers.
Figure 2
Figure 2
Comparison of mean change in heart rates from baseline between ivabradine + beta-blocker vs beta-blocker alone. BB: Beta blockers.
Figure 3
Figure 3
Comparison of mean change in heart rates from baseline between ivabradine + beta-blocker vs beta-blocker alone including only randomized controlled trials. BB: Beta blockers.
Figure 4
Figure 4
Comparison of Mantel-Haenszel risk ratio for all cause mortality between ivabradine + beta-blocker vs beta-blocker alone. BB: Beta blockers.
Figure 5
Figure 5
Comparison of Mantel-Haenszel risk ratio for cardiovascular mortality between ivabradine + beta-blocker vs beta-blocker alone. BB: Beta blockers.
Figure 6
Figure 6
Comparison of Mantel-Haenszel risk ratio for heart failure hospitalization between ivabradine + beta-blocker vs beta-blocker alone. BB: Beta blockers.
Figure 7
Figure 7
Comparison of difference in means of 6-min walking distance between ivabradine + beta-blocker vs beta-blocker alone. BB: Beta blockers.
Figure 8
Figure 8
Comparison of difference in means of ejection fraction between ivabradine + beta-blocker vs beta-blocker alone. BB: Beta blockers.
See this image and copyright information in PMC

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