Does the addition of losartan improve the beneficial effects of ACE inhibitors in patients with anterior myocardial infarction? A pilot study.
OBJECTIVE
To verify the efficacy of the combination of captopril (75 mg day) and losartan (25 mg/day) in early postinfarction phases of reperfused anterior acute myocardial infarction.


METHODS
99 patients, hospitalised for suspected anterior acute myocardial infarction within four hours from the onset of symptoms, were randomised into two groups: group A included 50 patients who received captopril 75 mg/day and placebo; group B included 49 patients who received captopril 75 mg/day within three days of admission plus losartan 12.5 mg, as a first dose, and 25 mg/day successively. An additional 23 patients with anterior acute myocardial infarction received losartan 25 mg alone and acted as controls (group C) to check the effects of losartan on plasma angiotensin II (AII) concentrations. Noradrenaline (norepinephrine) (NA) and AII plasma concentrations were measured on the third and 10th day after admission in 93 patients (35 from group A, 35 from group B, and 23 from group C). 90 days after admission patients underwent echocardiography to determine end systolic volume (ESV) and ejection fraction (EF).


RESULTS
Patients in groups A and B were similar with regard to age, sex, creatine kinase peak, EF, ESV, and risk factors. Group B (captopril plus losartan) patients showed a significant reduction in mean (SD) systolic blood pressure within the group (basal 128 (10) mm Hg; 10 days after admission 105 (9) mm Hg, p < 0.001), and in comparison with group A (captopril) patients (basal 127 (11) mm Hg; 10 days after admission 116 (10) mm Hg, p < 0. 001). Diastolic blood pressure was also lower in group B patients versus group A (66 (11) v 77 (11) mm Hg). Group C (losartan) patients also showed a significant reduction in systolic blood pressure (131 (13) mm Hg down to 121 (12) mm Hg, p < 0.001). Neither NA nor AII plasma concentrations in groups A and B differed significantly in basal samples (NA 673 (138) v 675 (141) pg/ml; AII 12.77 (4.79) v 12.65 (4.71) pg/ml) or 10 days after admission (NA 283 (93) v 277 (98) pg/ml; AII 5.31 (2.25) v 6.09 (3.31) pg/ml). However, patients in group C had higher plasma concentrations of AII (14.79 (5.7) pg/ml on the third day and 7.98 (4.92) pg/ml on the 10th day) than patients in either group A or B (p = 0.006). After 90 days following treatment, group B (captopril plus losartan) patients had a smaller ESV than patients in group A (captopril) and group C (losartan).


CONCLUSIONS
The data suggest that the combination of captopril plus losartan is feasible in the early treatment of acute myocardial infarction patients, and it appears that this combination has more effect on ESV than captopril alone in the short term.
Di Pasquale
P
P
Division of Cardiology, "Paolo Borsellino",GF Ingrassia Hospital, Via Val Platani 3, 90144 Palermo, Italy.
Bucca
V
V
Scalzo
S
S
Cannizzaro
S
S
Giubilato
A
A
Paterna
S
S
D000368:Aged; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D009638:Norepinephrine / Q000097:blood; D010865:Pilot Projects; D016037:Single-Blind Method
D000806:Angiotensin-Converting Enzyme Inhibitors; D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D000804:Angiotensin II; D002216:Captopril; D019808:Losartan; D009638:Norepinephrine