Additional beneficial effects of canrenoate in patients with anterior myocardial infarction on ACE-inhibitor treatment. A pilot study.
BACKGROUND
Recent evidence suggests that, via the mineralocorticoid receptors present in cardiovascular tissues, aldosterone exerts profibrotic effects, and that partial aldosterone escape occurs during ACE-inhibitor treatment.


METHODS
A double-blind, randomized study was performed in order to evaluate the feasibility, tolerability, and the effects of the administration of 25 mg/day of canrenoate plus captopril versus captopril alone to patients with anterior acute myocardial infarction (AMI) unsuitable for or not receiving thrombolytic treatment and to patients in whom such treatment resulted or did not result in reperfusion. One hundred eighty-seven patients with anterior AMI were included in the present study. In all cases serum creatinine concentrations and serum K concentrations were < 2.0 mg/dl and < 5.5 mmol/l respectively. The patients were randomized in two groups: the canrenoate group included 94 patients who received captopril and 25 mg i.v. of canrenoate (1 mg/hour for the first 72 hours and then orally 25 mg/day) whereas the placebo group (93 patients) received captopril and placebo. On admission and on days 10, 90 and 180 all patients underwent echocardiography in order to determine the end-systolic volume (ESV), the ejection fraction (EF), the end-diastolic diameter, the E/A ratio, the E deceleration time as well as the isovolumetric relaxation time (IVRT) and the E and A peak velocities.


RESULTS
Unreperfused patients did not show patency of the infarct-related artery whereas in reperfused patients this vessel was patent (7-10 days after AMI). The two groups were similar in age, sex, incidence of diabetes, smoking habits, hypertension, creatine kinase enzymatic peak, adjuvant therapy, baseline EF, ESV, and incidence of coronary artery bypass grafting/coronary angioplasty. Following 10 days of treatment (canrenoate group), only 9 patients presented with serum K and creatinine concentrations respectively > 5.5 mmol/l and > 2.0 mg/dl. Among those patients receiving canrenoate, the mitral E/A ratio was higher compared to the placebo group (p = 0.001) whereas the ESV was significantly reduced (p < 0.05). The deceleration time for reperfused patients receiving canrenoate was higher than that observed for reperfused patients in the placebo group. The intragroup EF was significantly increased (p = 0.042). Compared to the placebo group, the IVRT was significantly higher for unreperfused patients receiving canrenoate than in the placebo group (p = 0.001). Serum creatinine, blood urea and K levels as well as the incidence and extent of vessel disease were similar for both groups. No side effects were observed during the study period.


CONCLUSIONS
Our data suggest that the combination of captopril plus canrenoate is feasible for the initial treatment of patients presenting with AMI. Besides, compared to captopril alone it is more efficacious in improving the E/A ratio, the ESV, the EF, and the IVRT.
Division of Cardiology Paolo Borsellino, G.E Ingrassia Hospital, Palermo, Italy. LEHDi@tin.it
P
P
Di Pasquale
S
S
Cannizzaro
A
A
Giubilato
M G
MG
Vitrano
A
A
Scandurra
F
F
Giambanco
G
G
Saccone
F M
FM
Sarullo
S
S
Paterna
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002191:Canrenoic Acid / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D015425:Myocardial Reperfusion / Q000379:methods*; D010865:Pilot Projects; D015912:Thrombolytic Therapy; D017211:Treatment Failure; D014463:Ultrasonography
D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D002191:Canrenoic Acid; D002216:Captopril