Angiotensin-converting enzyme inhibition as an adjunct to pulmonary rehabilitation in COPD

Abstract

Rationale: Epidemiological studies in older individuals have found an association between use of ACE-inhibition (ACE-I) therapy and preserved locomotor muscle mass, strength and walking speed. ACE-I therapy might therefore have a role in the context of pulmonary rehabilitation. Objectives: We investigated the hypothesis that enalapril, an ACE-inhibitor, would augment the improvement in exercise capacity seen during pulmonary rehabilitation. Methods: We performed a double-blind, placebo-controlled, parallel-group randomised controlled trial. COPD patients, with at least moderate airflow obstruction and taking part in pulmonary rehabilitation, were randomised to either 10 weeks therapy with an ACE-inhibitor (10mg enalapril) or placebo. Measurements: The primary outcome measurement was the change in peak power (assessed using cycle ergometry) from baseline. Main Results: Eighty patients were enrolled, seventy-eight randomised (age 67±8years, FEV1 48±21% predicted), and sixty-five completed the trial (34 placebo, 31 ACE-inhibitor). The ACE-inhibitor treated group demonstrated a significant reduction in systolic blood pressure (Δ-16mmHg, 95% CI -22 to -11) and serum ACE activity (Δ-18IU/L, 95% CI -23 to -12) versus placebo (between group differences p<0.0001). Peak power increased significantly more in the placebo group (placebo Δ+9 Watts, 95% CI 5 to 13 vs. ACE-I Δ+1 Watt, 95% CI -2 to 4, between group difference 8 Watts, 95% CI 3 to 13, p=0.001). There was no significant between group difference in quadriceps strength or health-related quality of life. Conclusion: Use of the ACE-inhibitor enalapril alongside a programme of pulmonary rehabilitation, in patients without an established indication for ACE-inhibition, reduced the peak work rate response to exercise training in COPD patients. Clinical trial registration available at www.controlled-trials.com, ID ISRCTN79038750.