OBJECTIVE--Comparison of the first dose responses to low dose constant rate infusions of diacid angiotensin converting enzyme (ACE) inhibitors. DESIGN--Double blind, randomised, placebo controlled, parallel group prospective study. SETTING--General hospital inpatient admissions for supervised diuretic withdrawal (24-48 hours) and the introduction of ACE inhibitor treatment. PATIENTS--36 unselected elderly (aged 60-87 years) patients with symptomatic but stable chronic cardiac failure (New York Heart Association grades II-IV). ACE inhibitor started under double blind conditions with blood pressure monitoring. INTERVENTION--Patients were randomly allocated to receive intravenous placebo (saline), enalaprilat (1.5 mg over six hours) or perindoprilat (1 mg over six hours) by constant rate intravenous infusion (5 ml/hour). The protocol allowed for discontinuation of infusion if mean arterial blood pressure fell by 30% from the value before treatment. MAIN OUTCOME MEASURES--Blood pressure and heart rate responses, drug concentration, plasma renin, and ACE activities. RESULTS--The three groups had similar age, severity of heart failure, diuretic dose before treatment, plasma renin activity, and serum electrolyte state. All patients remained symptom free throughout the study. Infusions were only ended early with active treatment: 5/12 perindoprilat cases, (mean (SD) dose 0.88 (0.18) mg, and 5/12 enalaprilat cases (mean (SD) dose 1.2 (0.4) mg. Both active treatments lowered mean arterial pressure until discontinuation of infusion. Heart rate was not altered. Two patients (one perindoprilat, one enalaprilat) showed transient and symptom free renal impairment. CONCLUSIONS--Slow intravenous infusion of diacid ACE inhibitors may allow safe initiation of treatment in patients with heart failure and with activated renin angiotensin systems. The similar effects of intravenous perindoprilat and enalaprilat on blood pressure contrast with previously reported differences when perindopril and enalapril were given orally.
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