BLOOD-PRESSURE RESPONSE TO THE 1ST DOSE OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS IN CONGESTIVE-HEART-FAILURE

Angiotensin-converting enzyme (ACE) inhibitors improve survival in hea rt failure and delay progression to clinical heart failure in patients with left ventricular dysfunction after myocardial infarction. Increa sing numbers of older patients are being considered for such treatment . However, there are reports of excessive and prolonged decreases in b lood pressure (BP) after the first dose of some ACE inhibitors. We hav e studied the hemodynamics, pharmacokinetics and neurohumoral response s to the first dose of oral captopril 6.25 mg, enalapril 2.5 mg, perin dopril 2.0 mg, intravenous enalaprilat 1.5 mg, and perindoprilat 1.0 m g, compared with oral or intravenous placebo in 6 parallel groups of 1 2 elderly patients each with moderate-to-severe (New York Heart Associ ation classes II-IV) heart failure. Oral dosing with active drugs led to different temporal responses. After captopril, there was an early s hort-lived decrease in BP. Enalapril led to a later long-lasting decre ase, but perindopril was not different from placebo. Intravenous enala prilat and intravenous perindoprilat each lowered BP to a similar exte nt. The doses of drugs used appeared to be comparable because plasma A CE inhibition was similar following perindopril or enalapril and also comparing perindoprilat and enalaprilat. These studies indicate that o ral ACE inhibitors have different profiles of acute BP changes after t he first dose. The explanation is not clear, but could include physico chemical differences in the interaction between prodrug ester and diac id metabolites leading to differences in tissue distribution and local enzyme inhibition.