Use of ivabradine in heart failure with reduced ejection fraction
- Wilson S Colucci, MD
Wilson S Colucci, MD
- Section Editor — Heart Failure
- Professor of Medicine
- Boston University School of Medicine
The selective sinus node inhibitor ivabradine reduces the risk of hospital admission for heart failure (HF) and death from HF in patients with HF with reduced ejection fraction (HFrEF) . This benefit is associated with reduced sinus rate.
The use of ivabradine in the treatment of HFrEF is discussed here. An overview of therapy of HFrEF and the pharmacologic therapy of HFrEF are presented separately. (See "Overview of the therapy of heart failure with reduced ejection fraction" and "Pharmacologic therapy of heart failure with reduced ejection fraction".)
RATIONALE AND MECHANISM OF ACTION
Heart rate as a therapeutic target — Heart rate reduction is a potential therapeutic target in patients with heart failure with reduced ejection fraction (HFrEF) since an elevated heart rate is associated with worse cardiovascular outcomes. An elevated heart rate reflects, in part, activation of the sympathetic nervous system and withdrawal of parasympathetic activity, which are components of the neurohumoral response to HF . An elevated plasma norepinephrine concentration is a marker for poor survival in these patients . It has been unclear whether heart rate is a determinant of prognosis, or simply a marker for increased sympathetic tone. While the relative contributions of increased heart rate versus the underlying neurohumoral abnormalities are difficult to determine, the beneficial effects of ivabradine, an agent that acts solely by decreasing heart rate (discussed below), suggests that an elevated heart rate, per se, contributes to adverse outcomes in patients with HFrEF. Possible detrimental effects of elevated heart rate include heart rate-related increases in myocardial oxygen consumption and shear stress and decreases in myocardial perfusion . (See "Predictors of survival in heart failure due to systolic dysfunction", section on 'Neurohumoral activation and heart rate'.)
Heart rate lowering drugs have differing effects on heart failure — While some heart rate lowering drugs are beneficial in patients with HFrEF, various types of heart rate lowering drugs have differing mechanisms of action, as well as differing effects on outcomes in patients with HFrEF.
Beta blockers and ivabradine both decrease heart rate and improve clinical outcomes in patients with HFrEF, but they have different mechanisms of action as discussed below. For both drugs, there is evidence that clinical benefit is related to heart rate lowering, although beta blockers likely have other beneficial effects. (See "Use of beta blockers in heart failure with reduced ejection fraction".)
- Swedberg K, Komajda M, Böhm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 2010; 376:875.
- Packer M. The neurohormonal hypothesis: a theory to explain the mechanism of disease progression in heart failure. J Am Coll Cardiol 1992; 20:248.
- Cohn JN, Levine TB, Olivari MT, et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 1984; 311:819.
- Dobre D, Borer JS, Fox K, et al. Heart rate: a prognostic factor and therapeutic target in chronic heart failure. The distinct roles of drugs with heart rate-lowering properties. Eur J Heart Fail 2014; 16:76.
- http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206143Orig1s000lbl.pdf (Accessed on June 25, 2015).
- Yancy CW, Jessup M, Bozkurt B, et al. 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol 2016; 68:1476.
- Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016; 37:2129.
- http://pi.amgen.com/united_states/corlanor/corlanor_mg.pdf (Accessed on August 03, 2015).
- http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206143Orig1s000lbl.pdf (Accessed on June 12, 2015).
- Dierckx R, Cleland JG, Parsons S, et al. Prescribing patterns to optimize heart rate: analysis of 1,000 consecutive outpatient appointments to a single heart failure clinic over a 6-month period. JACC Heart Fail 2015; 3:224.
- Teerlink JR. Ivabradine in heart failure--no paradigm SHIFT…yet. Lancet 2010; 376:847.
- Martin RI, Pogoryelova O, Koref MS, et al. Atrial fibrillation associated with ivabradine treatment: meta-analysis of randomised controlled trials. Heart 2014; 100:1506.
- Böhm M, Swedberg K, Komajda M, et al. Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet 2010; 376:886.
- Böhm M, Borer J, Ford I, et al. Heart rate at baseline influences the effect of ivabradine on cardiovascular outcomes in chronic heart failure: analysis from the SHIFT study. Clin Res Cardiol 2013; 102:11.
- RATIONALE AND MECHANISM OF ACTION
- Heart rate as a therapeutic target
- Heart rate lowering drugs have differing effects on heart failure
- Mechanism of action of ivabradine therapy
- SELECTION OF CANDIDATES FOR IVABRADINE THERAPY
- Major society guidelines
- CLINICAL USE
- Initiation of therapy
- Adverse effects
- In addition to beta blocker therapy
- Comparison to beta blocker therapy
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS