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 (AII) is thought to be a ma jor contributor to the hemodynamic response to angiotensin-converting enzyme inhibition (ACE-in) therapy. However, angiotensin II (A-II) pla sma levels may rebound during ACE-in treatment. The study sought to ve rify the feasibility, safety, and tolerability of the combination of c aptopril (75 mg/d) plus losartan (25 mg/d). We also wished to establis h whether the combination was able to avoid the increase of angiotensi n II resulting from losartan treatment in early postinfarction phases of reperfused anterior acute myocardial infarction (AMI). Forty-four p atients, hospitalized for suspected anterior AMI within 4 hours from t he onset of symptoms, suitable for thrombolysis (first episode), Killi p class I-II and reperfused, receiving 75 mg/d of captopril within 3 d ays from admission, and with systolic blood pressure (BP) >120 mmHg we re randomized (single-blind) into two groups: Group A included 22 pati ents (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 captopr il 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 (N E) and A-II levels were measured on the 3rd and 10th days after admiss ion. The two groups were similar with regard to age, sex, creatinine k inase 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 aft er admission. In group A, BP was 122 +/- 9 mmHg, and 10 days after adm ission BP was 118 +/- 11 mmHg. NE and A-II values did not show signifi cant differences in basal samples. At 10 days after admission values w ere NE 298 +/- 90 versus 272 +/- 86 pg/mL and A-II 6.07 +/- 2.97 versu s 5.29 +/- 2.08 pg/mL for the two groups. Our data suggest, for the fi rst 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.