Heart Failure NYHA Class III Clinical Trial
Official title:
Mechanism(s) Underlying Cardiovascular Effects of ARB/NEP Inhibition - Aim 2
This study tests the hypothesis that endogenous bradykinin contributes to effects of a combined angiotensin receptor blocker/neprilysin inhibitor (LCZ696 or Entresto)
Patients with heart failure (HF) with reduced ejection fraction who qualify for the study will undergo a three-week run-in period in which any prior angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker they were taking will be discontinued and they will be given valsartan 80 mg bid in a single-blind fashion. After the run-in, subjects will undergo four study periods in random order. During two study periods they will receive enalapril 10 mg bid and during two they will receive sacubitril/valsartan (LCZ696) 200 mg bid for seven days. On the seventh day or each period, subjects will complete a study day in which they are randomized to receive either the bradykinin B2 receptor blocker icatibant or placebo intravenously. Each study period will be separated by a three-week washout during which subjects receive valsartan 80 mg bid. ;
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