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Randomised clinical trials in COPD
S48 The Effect of Angiotensin-Converting Enzyme Inhibition on Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease: A Randomised Controlled Trial
  1. D Shrikrishna1,
  2. RJ Tanner1,
  3. JY Lee2,
  4. SA Natanek2,
  5. A Lewis2,
  6. PB Murphy3,
  7. N Hart3,
  8. J Moxham4,
  9. H Montgomery5,
  10. PR Kemp2,
  11. MI Polkey1,
  12. NS Hopkinson1
  1. 1National Heart and Lung Institute, NIHR Respiratory Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust & Imperial College, London, UK
  2. 2Molecular Medicine Section, National HeartLung Institute, South Kensington Campus, Imperial College, London, UK
  3. 3Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, NIHR Comprehensive Biomedical Research Centre, London, UK
  4. 4Department of Asthma, Allergy and Respiratory Science, Division of Asthma, Allergy and Lung Biology, King’s College, London, UK
  5. 5Institute for Human Health and Performance, University College, London, UK


Introduction Skeletal muscle impairment is a well recognised complication of COPD, predicting mortality in severe disease.1 Evidence from animal models, genetic studies and observational cohorts suggest a role for the renin-angiotensin system in control of muscle phenotype.2 We hypothesised that angiotensin-converting enzyme (ACE) inhibition would have a beneficial effect on quadriceps function in patients with COPD.

Methods A single-centre, double-blind randomised controlled parallel-group trial investigating the effect of fosinopril versus placebo on quadriceps muscle dysfunction in COPD patients with quadriceps weakness. Muscle weakness was defined as a quadriceps maximum voluntary contraction (QMVC) less than 120% of the body mass index.1

Measurements The primary outcome was change in non-volitional quadriceps endurance at 3 months, measured using repetitive magnetic stimulation. QMVC, mid-thigh CT cross-sectional area (MTCSA), incremental shuttle walk distance (ISWD) and serum inflammatory markers were secondary outcomes.

Results 80 patients were enrolled (mean(SD), 65(8) years, FEV1 43(21)% predicted, 53% male). 67 patients (31 fosinopril and 36 placebo) completed the trial, with the treatment group demonstrating a significant reduction in systolic blood pressure (Δ-10.5mmHg, 95%CI –19.9 to –1.1, p=0.03) and serum ACE activity (Δ-20.4units/L, 95%CI –31.0 to –9.8, p<0.001) compared to placebo. At 3 months, no significant difference was observed in quadriceps muscle endurance half-time (fosinopril Δ5.1s, 95%CI –4.3 to 14.5, p=0.27 vs. placebo Δ4.6s, 95%CI –5.8 to 15.1, p=0.37; between group Δ0.5s, 95%CI –13.3 to 14.3, p=0.94). QMVC improved significantly in both groups (fosinopril Δ1.1kg, 95%CI 0.03 to 2.2, p=0.045 vs. placebo Δ3.6kg, 95%CI 2.1 to 5.0, p<0.0001) with a greater increase in the placebo arm (between group Δ2.5kg, 95%CI 0.7 to 4.3, p<0.01). There was no significant change in MTCSA (p=0.09), ISWD (p=0.51) or serum inflammatory markers (C-reactive protein, p=0.17) between the groups. Stratification based on ACE genotype did not influence study outcomes.

Conclusion This randomised controlled trial found that ACE-inhibition did not improve quadriceps function in a COPD population with quadriceps weakness. Study funded by the Medical Research Council. Trial registration: NCT01014338.

  1. Swallow EB, et al. Thorax 2007; 62:115–20.

  2. Shrikrishna D, et al. Clin Sci 2012; 123:487–98.

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