Influence of angiotensin converting enzyme inhibition on exercise performance and clinical symptoms in chronic heart failure: a multicentre, double-blind, placebo-controlled trial

Abstract

One hundred and seven patients with chronic heart failure (NYHA class II to IV) stabilized on digitalis and/or diuretics, recruited from 11 centres were randomized into a double-blind, placebo-controlled study to assess the effect of 12 weeks of cilazapril therapy on exercise tolerance and clinical status. Thirty-five patients were randomized to placebo and 72 to cilazapril at a starting dose of 1 mg daily; titration to cilazapril 2.5 mg at week 4 and 5 mg at week 8 (or matching placebo) was carried out in patients who did not improve clinically. Demographic characteristics, including exercise test duration increased from 402 s (+/- 17 SEM) at baseline to 462 s (+/- 19 SEM) at week 12 for the cilazapril group (+15%) and from 405 s (+/- 23 SEM) at baseline to 408 s (+/- 30 SEM) at week 12 in patients on placebo (+1%) (P < 0.001). In the placebo group, patients able to exercise for more than 6 min at baseline showed an increase in exercise duration at week 12 while those able to exercise for up to 6 min at baseline showed a decrease (P = ns). In contrast, cilazapril-treated patients showed an increase in exercise tolerance regardless of baseline exercise test duration; patients with the most impaired exercise tolerance at baseline showed a greater improvement than patients with mildly impaired baseline exercise tolerance (P < 0.05 vs placebo). NYHA class improved by at least one grade in 51% of the cilazapril group vs 32% in the placebo group (P = ns). At the end of the trial, 15% of the patients were non-responders on cilazapril vs 41% on placebo (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

A meta‐analysis of the effect of angiotensin‐converting enzyme inhibitors on functional capacity in patients with symptomatic left ventricular systolic dysfunction

“…Because of missing information on allocation concealment it was not possible to score for study quality properly. However, these 13 studies were large multi‐centre double blind parallel group trials [7,8,12–16,29,31–35] wherein the allocation concealment might be considered adequate.…”

“…We chose the random‐effects model for continuous data, which provides the weighted mean difference with 95% confidence interval. All values presented as standard error of mean in the original studies [29,31,34] were recalculated to their standard deviations. In case of unreported standard deviations in the post‐treatment values the pre‐treatment values were substituted [7,8,12,30].…”

Neuroendocrine activation after myocardial infarction: causes and consequences

“…In heart failure, calcium 55 antagonists generally increase renin-angiotensin and sympathetic nervous system activity.42 It is unclear whether newer dihydropiridine calcium antagonists have a similar effect on these systems.…”

Optimal management of sarcopenia

“…Observational studies have shown that the long-term use of ACE inhibitors was associated with a lower decline in muscle strength and walking speed in older hypertensive people and a greater lower limb lean muscle mass when compared with users of other antihypertensive agents. 110,111 Several studies have shown that ACE inhibitors improved exercise capacity in younger people with heart failure and this was also confirmed in older people with heart failure, 110,112,113 no improvement in grip strength. 114 Although this could be largely attributed to improvements in cardiac function, skeletal muscle atrophy is also associated with chronic heart failure so the evidence in muscle gains should not be discounted.…”