TY  - JOUR
A1  - Shrikrishna, D
A1  - Tanner, RJ
A1  - Lee, JY
A1  - Natanek, A
A1  - Lewis, A
A1  - Murphy, PB
A1  - Hart, N
A1  - Moxham, J
A1  - Montgomery, HE
A1  - Kemp, PR
A1  - Polkey, MI
A1  - Hopkinson, NS
JF  - CHEST
SN  - 0012-3692
UR  - http://dx.doi.org/10.1378/chest.13-2483
ID  - discovery1456514
N2  - BACKGROUND:  Skeletal muscle impairment is a recognized complication of COPD, predicting mortality in severe disease. Increasing evidence implicates the renin-angiotensin system in control of muscle phenotype. We hypothesized that angiotensin-converting enzyme (ACE) inhibition would improve quadriceps function and exercise performance in COPD.
METHODS:  This double-blind, randomized placebo-controlled trial investigated the effect of the ACE inhibitor, fosinopril, on quadriceps function in patients with COPD with quadriceps weakness. Primary outcomes were change in quadriceps endurance and atrophy signaling at 3 months. Quadriceps maximum voluntary contraction (QMVC), mid-thigh CT scan of the cross-sectional area (MTCSA), and incremental shuttle walk distance (ISWD) were secondary outcomes.
RESULTS:  Eighty patients were enrolled (mean [SD], 65 [8] years, FEV1 43% [21%] predicted, 53% men). Sixty-seven patients (31 fosinopril, 36 placebo) completed the trial. The treatment group demonstrated a significant reduction in systolic BP (??10.5 mm Hg; 95% CI, ?19.9 to ?1.1; P = .03) and serum ACE activity (??20.4 IU/L; 95% CI, ?31.0 to ?9.8; P < .001) compared with placebo. No significant between-group differences were observed in the primary end points of quadriceps endurance half-time (?0.5 s; 95% CI, ?13.3-14.3; P = .94) or atrogin-1 messenger RNA expression (??0.03 arbitrary units; 95% CI, ?0.32-0.26; P = .84). QMVC improved in both groups (fosinopril: ?1.1 kg; 95% CI, 0.03-2.2; P = .045 vs placebo: ?3.6 kg; 95% CI, 2.1-5.0; P < .0001) with a greater increase in the placebo arm (between-group, P = .009). No change was shown in the MTCSA (P = .09) or ISWD (P = .51).
CONCLUSIONS:  This randomized controlled trial found that ACE inhibition, using fosinopril for 3 months, did not improve quadriceps function or exercise performance in patients with COPD with quadriceps weakness.
N1  - PubMed ID: 24556825
© 2014 AMERICAN COLLEGE OF CHEST PHYSICIANS. This is a Wellcome-Trust-compliant open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/).
IS  - 4
EP  -  940
SP  - 932 
AV  - public
VL  - 146
Y1  - 2014/10/01/
TI  - A Randomized Controlled Trial of Angiotensin-Converting Enzyme Inhibition for Skeletal Muscle Dysfunction in COPD
ER  -