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Effect of Perindopril or Leucine on physical performance in older people with sarcopenia: the LACE randomised controlled trial

Authors
  • Achison, M
  • Adamson, S
  • Akpan, A
  • Aspray, T
  • Avenell, A
  • Band, M
  • Bashir, T
  • Burton, L
  • Cvoro, V
  • Donnan, P
  • Duncan, G
  • George, J
  • Gordon, A
  • Gregson, C
  • Hapca, A
  • Henderson, E
  • Hume, C
  • Jackson, T
  • Kemp, P
  • Kerr, S
  • And 18 more
Publication Date
Jan 17, 2022
Source
Spiral - Imperial College Digital Repository
Keywords
License
Green
External links

Abstract

Background: This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. Methods: Placebo-controlled, parallel group, double-blind, randomised two-by-two factorial trial. We recruited adults aged ≥70 years with sarcopenia, defined as low gait speed (<0.8 m/s on 4m walk) and/or low handgrip strength (women <20kg, men <30kg) plus low muscle mass (using sex and BMI category-specific thresholds derived from normative UK BioBank data) from 14 UK centres. Eligible participants were randomised to perindopril 4mg or placebo, and to oral leucine powder 2.5g or placebo thrice daily. The primary outcome was the between-group difference in the Short Physical Performance Battery (SPPB) score over 12-month follow-up by repeated-measures mixed models. Results were combined with existing systematic reviews using random-effects meta-analysis to derive summary estimates of treatment efficacy. Results: We screened 320 people and randomised 145 participants compared to an original target of 440 participants. For perindopril (n=73, mean age 79 [SD 6], female sex 39 [53%], mean SPPB 7.1 [SD 2.3]) vs no perindopril (n=72, mean age 79 [SD 6], female sex 39 [54%], mean SPPB 6.9 [SD 2.4]), medianadherence to perindopril was lower (76% vs 96%; p<0.001). Perindopril did not improve the primary outcome (adjusted treatment effect -0.1 points [95%CI -1.2 to 1.0], p=0.89). No significant treatment benefit was seen for any secondary outcome including muscle mass (adjusted treatment effect -0.4kg [95%CI -1.1 to 0.3], p=0.27). More adverse events occurred in the perindopril group (218 vs 165) but falls rates were similar. For leucine (n=72, mean age 78 [SD 6], female sex 38 [53%], mean SPPB 7.0 [SD 2.1]) vs no leucine (n=72, mean age 79 [SD 6], female sex 40 [55%], mean SPPB 7.0 [SD 2.5]), 5 median adherence was the same in both groups (76% vs 76%; p=0.99). Leucine did not improve the primary outcome (adjusted treatment effect 0.1 point [95%CI -1.0 to 1.1], p=0.90). No significant treatment benefit was seen for any secondary outcome including muscle mass (adjusted treatment effect -0.3kg [95%CI -1.0 to 0.4], p=0.47). Meta-analysis of ACEi / angiotensin receptor blocker trials showed no clinically important treatment effect for the SPPB (between-group difference -0.1 points [95%CI -0.4 to 0.2]). Conclusions: Neither perindopril nor leucine improved physical performance or muscle mass in this trial; meta-analysis did not find evidence of efficacy of either ACE inhibitors or leucine as treatments to improve physical performance.

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