Pharmacological Treatment of Heart Failure with Preserved Ejection Fraction

Abstract

Heart failure with preserved ejection fraction is a socioeconomic burden in Japan as well as other developed countries. Diuretics are widely used to attenuate symptoms and signs of congestion in both heart failure with preserved and reduced ejection fraction, although their effects on long-term prognosis of both phenotypes of heart failure have not been demonstrated because of an ethical difficulty in designing a randomized and prospective clinical trial. Guidelines do not provide any guidance on therapy choice, and physicians blindly choose furosemide among loop diuretics in current clinical settings. However, several clinical studies have suggested that the effects of loop diuretics are not consistent, and that furosemide is not necessarily preferable as compared with other loop diuretics. We should pay attention to the choice of loop diuretics. Regarding the improvement of long-term prognosis, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, mineralocorticoid receptor blocker and β-blocker are proven effective for heart failure with reduced ejection fraction. However, none of these drugs have improved prognosis of heart failure with preserved ejection fraction in clinical trials. Observational studies and subanalysis of clinical trials suggest the benefits of these drugs in this phenotype of heart failure. All of clinical trials and observational studies present facts to us, and let us recognize that "one size fits all approach" may be a cause for a lack of evidence about the therapeutic strategy of heart failure with preserved ejection fraction until now. We have to make efforts to clarify characteristics of patients with heart failure and preserved ejection fraction to whom the administration of each drug provides benefits or do not.

Keywords: Diastole; Heart failure; Pharmacological intervention.

Fig. 1.

Difference of cumulative incidence of HFpEF and HFrEF among cohort studies. With an increase in age of study subjects, incidence of HFpEF enhances. (Figure was produced based on data of reference .) HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; PREVEND study, Prevention of Renal and Vascular Endstage Disease study; y.o., years old.

Fig. 2.

Kaplan-Meier survival curves of the HFpEF model rats of an untreated group, a group treated with low dose of bisoprolol (12.5 mg/kg/day) and a group treated with high dose of bisoprolol (250 mg/kg/day). The survival rate was improved by the administration of bisoprolol, and the effects of bisoprolol were dose-dependent. Copyright © 2014 John Wiley and Sons. All rights reserved. (Permission granted from the publisher of reference .) HFpEF, heart failure with preserved ejection fraction.

Fig. 3.

Kaplan-Meier curves showing the time to first occurrence of the prespecified outcome, cardiovascular death or unplanned hospitalization for any cardiovascular causes. The carvedilol group was further divided into a group treated with carvedilol > 7.5mg/day (n = 58, standard-dose group) and carvedilol ≤ 7.5mg/day (n = 62, low-dose group). Control group consists of HFpEF patients treated without β-blocker. Copyright © 2014 John Wiley and Sons. All rights reserved. (Permission granted from the publisher of reference .) CI, confidence interval; HFpEF, heart failure with preserved ejection fraction; HR, hazard ratio; No., number.