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Efficacy of ACE inhibitors in chronic heart failure with preserved ejection fraction — A meta analysis of 7 prospective clinical studies

https://doi.org/10.1016/j.ijcard.2011.01.081Get rights and content

Abstract

Background

The effect of ACE inhibitors on the prognosis of chronic heart failure patients with preserved left ventricular ejection fraction remains controversial.

Aims

To assess the impact of ACE inhibitors on the prognosis of chronic heart failure patients with preserved left ventricular ejection fraction.

Methods and results

Seven prospective studies evaluating the effect of ACE inhibitors compared to placebo or other classes of drugs, such as monotherapy or first-line therapy, on the prognosis of chronic heart failure patients with preserved left ventricular ejection fraction were included. A total of 2554 patients (mean age: 75.1 years, female: 58%) were recruited with an average follow up of 20.9 months. The primary etiology of heart failure with preserved ejection fraction was ischemic heart disease (33.7%), hypertension (69.1%) and diabetes mellitus (25.8%). Our results demonstrated that ACE inhibitors significantly reduced all-cause mortality (odds ratio, OR = 0.52; 95% Confidence Interval (CI), 0.41 to 0.64; P < 0.01). Furthermore, ACE inhibitors were able to reduce heart failure related rehospitalization or treatment over 20.9 months (p < 0.05) in a subgroup of patients aged over 75 years. However, death due to worsening of heart failure, heart failure related rehospitalization and any-cause readmission were not affected (OR = 0.88; 95% CI: 0.66 to 1.17; P = 0.37 for death due to worsening of heart failure; OR = 0.81; 95% CI: 0.63 to 1.05; P = 0.11 for heart failure related rehospitalization and OR = 0.88; 95% CI: 0.68 to 1.14; P = 0.33 for any-cause readmission, respectively).

Conclusions

In patients with chronic heart failure with preserved ejection fraction, ACE inhibitors reduced all-cause mortality without affecting mortality due to heart failure and any-cause rehospitalization.

Introduction

Heart failure with preserved left ventricular ejection fraction (HFPEF) has emerged as a major cause of morbidity and mortality worldwide. Epidemiological data revealed that the prevalence of HFPEF varied from 13%–74% in heart failure patients [1], [2], [3], [4] and that the mortality of HFPEF was the same as that of heart failure with reduced ejection fraction (HFREF) [5], [6]. Angiotensin-converting enzyme inhibitors (ACE inhibitors) constitute first-line treatment for patients with HFREF with proven effects of reducing mortality and morbidity; however, the effects of ACE inhibitors on HFPEF remain controversial. The aim of this meta-analysis was to assess the efficacy of ACE inhibitors in HFPEF patients, based on the results of the most recently published prospective studies.

Section snippets

Search strategy

We used PubMed, EMBASE, BIOSIS, the Cochrane Library (Issue 3, 2009) and OVID databases to search for all electronically registered clinical trials by means of the following keywords: angiotensin-converting enzyme inhibitor, captopril, enalapril, benazepril, perindopril, alacepril, zofenopril, cilazapril, quinapril, ramipril, spirapril, imidapril, delapril, lisinopril, fosinopril, trandolapril, heart failure with preserved ejection fraction, heart failure with normal left ventricular ejection

Literature search and study selection

After screening the titles and abstracts of all studies identified by the search strategy, 354 potentially relevant articles were selected and retrieved for more detailed information. Further screening for eligibility was performed by two independent reviewers using the inclusion and exclusion criteria (Fig. 1). Finally, 7 studies were included, all of which were published in English.

Overall study characteristics

The seven selected studies comprised a total of 2554 patients (mean age 75.1 years, female 58%, mean LVEF > 57.1%),

Discussion

The present study demonstrated that ACE inhibitors as monotherapy or first-line therapy resulted in a significant reduction in all-cause mortality in HFPEF. In addition, ACE inhibitors reduced heart failure related rehospitalization in a HEPEF subgroup aged > 75 or treatment over a period of 21 months. However, neither death due to worsening of heart failure nor all-cause rehospitalization was affected by ACE inhibitors.

There was no definite cut-off value for preserved ejection fraction. The

Acknowledgments

The study was supported by the Eleventh Five-Year Science and Technology Support Program of China (2006BAI01A04). The authors are grateful to Dr. Kai Hu from Wuerzburg University in Germany for assistance with the preparation of this manuscript. The authors of this manuscript have certified that they comply with the principles of ethical publishing in the International Journal of Cardiology [40].

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    These authors contributed equally to this work.

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