Safety, tolerability, and neurohormonal changes of the combination captopril plus losartan in the early postinfarction period: a pilot study.

Suppression of formation of angiotensin II (A-II) is thought to be a major contributor to the hemodynamic response to angiotensin-converting enzyme inhibition (ACE-in) therapy. However, angiotensin II (A-II) plasma levels may rebound during ACE-in treatment. The study sought to verify the feasibility, safety, and tolerability of the combination of captopril (75 mg/d) plus losartan (25 mg/d). We also wished to establish whether the combination was able to avoid the increase of angiotensin II resulting from losartan treatment in early postinfarction phases of reperfused anterior acute myocardial infarction (AMI). Forty-four patients, hospitalized for suspected anterior AMI within 4 hours from the onset of symptoms, suitable for thrombolysis (first episode), Killip class I-II and reperfused, receiving 75 mg/d of captopril within 3 days from admission, and with systolic blood pressure (BP) >120 mmHg were randomized (single-blind) into two groups: Group A included 22 patients (6 women and 16 men) and received captopril 75 mg/d and placebo. Group B included 22 patients (5 women and 17 men) and received captopril 75 mg/d within 3 days from admission plus losartan 12.5 mg, as the first dose, and 25 mg/d (BP >110 mmHg) successively. Norepinephrine (NE) and A-II levels were measured on the 3rd and 10th days after admission. The two groups were similar with regard to age, sex, creatinine kinase peak, ejection fraction, end-systolic volume, and risk factors. Group B (captopril plus losartan) showed a significant reduction of BP, from 124 +/- 8.5 mmHg to 108 +/- 6.4 mmHg, P < 0.001, at 10 days after admission. In group A, BP was 122 +/- 9 mmHg, and 10 days after admission BP was 118 +/- 11 mmHg. NE and A-II values did not show significant differences in basal samples. At 10 days after admission values were NE 298 +/- 90 versus 272 +/- 86 pg/mL and A-II 6.07 +/- 2.97 versus 5.29 +/- 2.05 pg/mL for the two groups. Our data suggest, for the first time, that the combination of captopril plus losartan is feasible and does not produce serious side effects. When losartan was added to ACE-in treatment, there was no significant increase in A-II.