Published online Feb 26, 2017. doi: 10.4330/wjc.v9.i2.182
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
Processing time: 114 Days and 11 Hours
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).
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.
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).
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.
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.