title: Ivabradine in the treatment of systolic heart failure - A systematic review and meta-analysis.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Mahesh Anantha Narayanan, Janani Baskaran, David G Benditt, Ganesh Raveendran, Division of Cardiovascular Diseases, University of Minnesota Medical Center, Minneapolis, MN 55455, United States.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Anantha Narayanan
authors.affiliation: Mahesh Anantha Narayanan, Janani Baskaran, David G Benditt, Ganesh Raveendran, Division of Cardiovascular Diseases, University of Minnesota Medical Center, Minneapolis, MN 55455, United States.
authors.forename: Yogesh N V
authors.initials: YN
authors.lastname: Reddy
authors.affiliation: Mahesh Anantha Narayanan, Janani Baskaran, David G Benditt, Ganesh Raveendran, Division of Cardiovascular Diseases, University of Minnesota Medical Center, Minneapolis, MN 55455, United States.
authors.forename: Janani
authors.initials: J
authors.lastname: Baskaran
authors.affiliation: Mahesh Anantha Narayanan, Janani Baskaran, David G Benditt, Ganesh Raveendran, Division of Cardiovascular Diseases, University of Minnesota Medical Center, Minneapolis, MN 55455, United States.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Deshmukh
authors.affiliation: Mahesh Anantha Narayanan, Janani Baskaran, David G Benditt, Ganesh Raveendran, Division of Cardiovascular Diseases, University of Minnesota Medical Center, Minneapolis, MN 55455, United States.
authors.forename: David G
authors.initials: DG
authors.lastname: Benditt
authors.affiliation: Mahesh Anantha Narayanan, Janani Baskaran, David G Benditt, Ganesh Raveendran, Division of Cardiovascular Diseases, University of Minnesota Medical Center, Minneapolis, MN 55455, United States.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Raveendran
keywords: Heart failure; Ivabradine