Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial.

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, randomized two-by-two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.8 m/s on 4 m walk) and/or low handgrip strength (women < 20 kg, men < 30 kg) plus low muscle mass (using sex and body mass index category-specific thresholds derived from normative UK BioBank data) from 14 UK centres. Eligible participants were randomized to perindopril 4 mg or placebo, and to oral leucine powder 2.5 g 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 randomized 145 participants compared with 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)] versus no perindopril [n = 72, mean age 79 (SD 6), female sex 39 (54%), mean SPPB 6.9 (SD 2.4)], median adherence 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 -0.4 kg (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)] versus no leucine [n = 72, mean age 79 (SD 6), female sex 40 (55%), mean SPPB 7.0 (SD 2.5)], 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 -0.3 kg (95%CI -1.0 to 0.4), P = 0.47]. Meta-analysis of angiotensin converting enzyme inhibitor/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.

Vasovagal syncope in the older person: differences in presentation between older and younger patients.

BACKGROUND: vasovagal syncope (VVS) has been diagnosed with increasing frequency in older people since the description of the head-up tilt table test (HUTT). There is, however, a paucity of research describing the clinical features of VVS in this group. To address this issue, we investigated the age distribution and differences in clinical characteristics associated with age in patients diagnosed with VVS by HUTT at our tertiary referral centre. METHODS: 1,060 consecutive patients with tilt-positive VVS were identified from a prospective database containing the demographic and clinical information of individuals assessed in our unit over a 10-year period. VVS was diagnosed with appropriate haemodynamic changes during HUTT and accompanying symptom reproduction. RESULTS: we found a bimodal age distribution with a small peak at 20-29 years and a larger peak at 70-79 years. Patients aged > or =60 years were less likely to report total loss of consciousness [odds ratio (OR) 0.50, 95% confidence interval (CI) = 0.38-0.64], near loss of consciousness (OR 0.53, 95% CI = 0.40-0.70) or palpitations (OR 0.45, 95% CI = 0.28-0.72) and more likely to present with unexplained falls (OR 2.33, 95% CI = 1.36-4.32). The typical provoking factors of prolonged standing (OR 0.55, 95% CI = 0.40-0.72), posture change (OR 0.61, 95% CI = 0.46-0.82) and hot environments (OR 0.57, 95% CI = 0.42-0.78) were also less common in older patients. CONCLUSION: in our large study population, VVS was more common in older patients. The clinical presentation differed significantly between the two groups. Older patients were less likely to give a typical history and therefore clinicians need to have a high index of suspicion when evaluating the older patient presenting with collapse or unexplained falls.