A randomized double-blind trial of enalapril in older patients with heart failure
and preserved ejection fraction: effects on exercise tolerance and arterial
distensibility.
Author(s): Kitzman DW, Hundley WG, Brubaker PH, Morgan TM, Moore JB, Stewart KP, Little WC.
Affiliation(s): Cardiology Section, Department of Internal Medicine, Wake Forest University
Health Sciences, Winston-Salem, NC, USA. dkitzman@wfubmc.edu
Publication date & source: 2010, Circ Heart Fail. , 3(4):477-85
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.
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