Should increasing the dose or adding an AT1 receptor blocker follow a relatively low dose of ACE inhibitor initiated in acute myocardial infarction?
OBJECTIVE
Based on currently available clinical evidence, we should use high-dose angiotensin converting enzyme inhibitor (ACE-I) for patients with acute myocardial infarction (MI), initiating it at incremental doses to avoid excessive hypotension. Recent animal studies with acute MI models failed to demonstrate the superiority of the combination therapy of ACE-I and angiotensin receptor blocker (ARB) to high-dose ACE-I treatment with comparable blood pressure reductions, which however might be attributed to the initiation of the targeted doses from the beginning. The aim of this study was to compare the effect of increasing the dose of ACE-I with that of adding ARB following a relatively low dose of ACE-I on the survival and left ventricular (LV) remodeling after MI.


METHODS
Rats underwent left coronary artery ligation and were treated with either ACE-I temocapril (5 mg/kg/day) or vehicle for 2 weeks, which was initiated 3 days after the surgery. The rats treated with temocapril were further randomly assigned to receive either high-dose temocapril (10 mg/kg/day) or combination therapy (temocapril 5 mg/kg/day+olmesartan 2.5 mg/kg/day), which was continued for another 6 weeks.


RESULTS
Both treatments similarly reduced the blood pressure, improved survival and ameliorated LV enlargement. In contrast, several parameters of LV function were significantly ameliorated only by the high-dose ACE-I but not by the combination therapy.


CONCLUSIONS
After the initiation of a relatively low dose of ACE-I in acute MI, increasing the dose of ACE-I or adding ARB may equally improve survival and LV remodeling in the setting of an equal hypotensive effect. Further study with a longer treatment protocol is required to determine whether the several favorable effects on LV function elicited only by the high-dose ACE-I treatment provide further beneficial effects on survival and LV remodeling compared with the combination therapy.
Sugie
Tadashi
T
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Japan.
Kagaya
Yutaka
Y
Takeda
Morihiko
M
Yahagi
Hirokazu
H
Takahashi
Chikako
C
Takahashi
Jun
J
Ninomiya
Mototsugu
M
Watanabe
Jun
J
Ichinohasama
Ryo
R
Tezuka
Fumiaki
F
Shirato
Kunio
K
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000235:genetics; D001920:Bradykinin / Q000097:blood; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D007093:Imidazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D023421:Models, Animal; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000737:chemistry; D009638:Norepinephrine / Q000097:blood; D000068557:Olmesartan Medoxomil; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D013841:Thiazepines / Q000008:administration & dosage* / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D024042:Collagen Type I; D024061:Collagen Type III; D007093:Imidazoles; D012333:RNA, Messenger; D013777:Tetrazoles; D013841:Thiazepines; D016212:Transforming Growth Factor beta; D000068557:Olmesartan Medoxomil; D009320:Atrial Natriuretic Factor; C055603:temocapril hydrochloride; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D001920:Bradykinin; D009638:Norepinephrine