A twelve-week, multicenter, randomized, double-blind, parallel-group, noninferiority trial of the antihypertensive efficacy and tolerability of imidapril and candesartan in adult patients with mild to moderate essential hypertension: the Iberian Multicenter Imidapril Study on Hypertension (IMISH).
OBJECTIVE
The aim of this study was to evaluate the annhypertensive efficacy and tolerability of the angiotensin-converting enzyme inhibitor imidapril and the angiotensin II type 1 receptor antagonist candesartan in mild to moderate essential hypertension.


METHODS
The trial was conducted at 8 centers across Portugal and Spain (the Iberian Multicenter Imidapril Study on Hypertension [IMISH] Study Group). Patients aged between 30 and 70 years with essential hypertension were eligible. Following a 2- to 4-week, single-blind, placebo run-in period, patients were randomly assigned to receive imidapril at doses of up to 20 mg/d, or candesartan at doses up to 16 mg/d, once daily in a double-blind, parallel-group design with a 12-week active-treatment period. To achieve the target systolic/diastolic blood pressure (SBP/DBP) of <140/<90 mm Hg, imidapril was titrated from 5 to 20 mg/d and candesartan was titrated from 4 to 16 mg/d. The main end point was the change from baseline in sitting blood pressure (BP) at trough. Secondary end points were response rate, evaluation of SBP and DBP throughout the study, and change of SBP and DBP in subgroup of patients with moderate hypertension, as well as incidence and severity of adverse events related to treatment reported throughout the study.


RESULTS
The intent-to-treat analysis consisted of 122 patients (imidapril group, 60 patients; 32 men, 28 women; mean [SD] age, 54.7 [9.2] years; white race, 59 [99.2%], Hispanic race, 1 [0.8%]; mean [SD] weight, 80.1 [12.8] kg; candesartan group, 62 patients; 36 men, 26 women; mean [SD] age, 53.9 [9.9] years; white race, 62 [100%]; mean [SD] weight, 77.6 [14.1] kg). In the imidapril group, the mean (SD) SBP and DBP were, respectively, 155.7 (10.2) and 96.7 (4.7) mm Hg at baseline and 139.4 (11.9) and 86.9 (7.6) mm Hg at the end of the 12-week treatment period (visit 5); SBP had decreased significantly from baseline, by 10.5% (mean [SD] Delta, -16.3 [12.3] mm Hg [95% CI, -19.5 to -13.1; P < 0.001]) and DBP had decreased significantly, by 10.1% (mean [SD] A, -9.8 [7.8] mm Hg [95% CI, -11.8 to -7.8; P < 0.001]). In the candesartan group, the mean (SD) SBP and DBP values were, respectively, 158.4 [11.2] and 98.3 [4.1] mm Hg at baseline and 139.8 [12.5] and 87.6 7.5] mm Hg at 12 weeks, corresponding to decreases of 11.7% in SBP (mean [SD] A, -18.6 [12.8] mm Hg [95% CI, -21.9 to -15.4; P < 0.001]) and 10.9% in DBP (mean [SD] A, -10.7 [7.3] mm Hg [95% CI, -12.5 to -8.8; P < 0.001]). Response rates were 78.3% (47/60) with imidapril and 69.4% (43/62) with candesartan, and BP normalization (<140/<90 mm Hg) was achieved in 55.0% (33/60) of patients with imidapril and 45.2% (28/62) of patients with candesartan. The incidences of adverse events were similar between groups. Most (73.9%) adverse events were mild in intensity. A serious adverse event (severe anxiety) was reported in the candesartan group and led to study discontinuation. No cases of dry cough or hypotension were reported.


CONCLUSIONS
The results of this study suggest that imidapril once daily at doses up to 20 mg and candesartan once daily at doses up to 16 mg were effective in this population of mildly to moderately hypertensive patients. Both treatments were well tolerated.
Palma Gámiz
José Luis
JL
Department of Cardiology, Hospital Ramón y Cajal, Madrid, Spain. jlpalma@meditex.es
Pêgo
Mariano
M
Contreras
Emilio Márquez
EM
Anglada
Montserrat Pujol
MP
Martínez
Josefina Oliván
JO
Esquerra
Eduardo Alegría
EA
Sagastagoitia Gorostiza
José Domingo
JD
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D048289:Imidazolidines / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011174:Portugal; D012720:Severity of Illness Index; D013030:Spain; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D048289:Imidazolidines; D013777:Tetrazoles; C065166:imidapril; C081643:candesartan