A Randomized Double-Blind Trial of Enalapril in Older Patients With Heart Failure and Preserved Ejection Fraction
- 1 July 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation: Heart Failure
- Vol. 3 (4), 477-485
- https://doi.org/10.1161/circheartfailure.109.898916
Abstract
Background—: Exercise intolerance is the primary symptom in older patients with heart failure and preserved ejection fraction (HFPEF); however, little is known regarding its mechanisms and therapy. Methods and Results—: Seventy-one stable elderly (70±1 years) patients (80% women) with compensated HFPEF and controlled blood pressure were randomized into a 12-month follow-up double-blind trial of enalapril 20 mg/d versus placebo. Assessments were peak exercise oxygen consumption; 6-minute walk test; Minnesota Living with HF Questionnaire; MRI; Doppler echocardiography; and vascular ultrasound. Compliance by pill count was excellent (94%). Twenty-five patients in the enalapril group versus 34 in the placebo group completed the 12-month follow-up. During follow-up, there was no difference in the primary outcome of peak exercise oxygen consumption (enalapril, 14.5±3.2 mL/kg/min; placebo, 14.3±3.4 mL/kg/min; P =0.99), or in 6-minute walk distance, aortic distensibility (the primary mechanistic outcome), left ventricle mass, or neurohormonal profile. The effect size of enalapril on peak exercise oxygen consumption was small (0.7%; 95% CI, 4.2% to 5.6%). There was a trend toward improved Minnesota Living with HF Questionnaire total score ( P =0.07), a modest reduction in systolic blood pressure at peak exercise ( P =0.02), and a marginal improvement in carotid arterial distensibility ( P =0.04). Conclusions—: In stable, older patients with compensated HFPEF and controlled blood pressure, 12 months of enalapril did not improve exercise capacity or aortic distensibility. These data, combined with those from large clinical event trials, suggest that angiotensin inhibition does not substantially improve key long-term clinical outcomes in this group of patients. This finding contrasts sharply with observations in HF with reduced EF and highlights our incomplete understanding of this important and common disorder.Keywords
This publication has 57 references indexed in Scilit:
- Effect of Losartan and Hydrochlorothiazide on Exercise Tolerance in Exertional Hypertension and Left Ventricular Diastolic DysfunctionThe American Journal of Cardiology, 2006
- Heart Failure: A Rose by Any Other Name?Congestive Heart Failure, 2006
- Relation of aortic distensibility determined by magnetic resonance imaging in patients ≥60 years of age to systolic heart failure and exercise capacityThe American Journal of Cardiology, 2002
- Importance of heart failure with preserved systolic function in patients ≥65 years of ageThe American Journal of Cardiology, 2001
- Reproducibility of cardiopulmonary exercise testing in elderly patients with congestive heart failureThe American Journal of Cardiology, 1998
- Effect of lisinopril and metoprolol on arterial distensibility.Hypertension, 1994
- Long-term effects of angiotensin-converting enzyme inhibition on the arterial wall of adult spontaneously hypertensive ratsThe American Journal of Cardiology, 1993
- Effect of enalapril on congestive heart failure treated with diuretics in elderly patients with prior myocardial infarction and normal left ventricular ejection fractionThe American Journal of Cardiology, 1993
- Ultrasonic measurement of the elastic modulus of the common carotid artery. The Atherosclerosis Risk in Communities (ARIC) Study.Stroke, 1992
- Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study.Circulation, 1984