Regression of left ventricular hypertrophy in hypertensive patients after 1 year of treatment with rilmenidine: a double-blind, randomized, controlled (versus nifedipine) study.
OBJECTIVE
To assess the effect of 1-year treatment with rilmenidine, an oxazoline compound that exerts its antihypertensive effects through binding to imidazoline receptors in the brainstem, on left ventricular hypertrophy (LVH) secondary to essential, mild-to-moderate hypertension [supine diastolic blood pressure (DBP)95-115 mmHg].


METHODS
We performed a double-blind, randomized, controlled (versus slow-release nifedipine) trial. Adjustment of treatment took place every month (M) between inclusion (MO) and an evaluation after 6 months (M6), then during M9 and after 1 year (M12) to achieve supine DBP values < or = 90 mmHg. Patients were dropped from our study if they had DBP> 95mmHg during two consecutive visits or DBP>115 mmHg on one occasion. The daily dosage of rilmenidine was 1 mg, and could be increased to 2 mg/day. The daily dosage of slow-release nifedipine was started from the beginning at the maximum dosage of 40 mg/day, so that there was no true adjustment of treatment despite the allocation of patients to a different unit in the case of DBP> 95 mmHg. The primary criterion was the change in left ventricular mass index (LVMI, g/m2), assessed by echocardiography, between MO and M12 for patients who completed the trial.


RESULTS
After a 1-month placebo run-in period, 76 patients were selected and 73 were included (35 treated with rilmenidine and 38 treated with nifedipine). Fifteen patients withdrew from the study and two completed the study with a major deviation from protocol, leaving 56 patients (24 treated with rilmenidine and 32 treated with nifedipine) for a per-protocol analysis. Baseline demographic characteristics and history of arterial hypertension for the rilmenidine and nifedipine groups were similar, for included patients and for those taken into account for the per-protocol analysis. Between MO and M12, DBP in members of the per-protocol population was adequately controlled for those in the rilmenidine group (102.7+/-4.6 versus 88.5+/-7.1 mmHg, respectively) and for those in the nifedipine group (102.7+/-5.1 versus 85.6+/-79 mmHg, respectively). During MO, LVMI of patients in the rilmenidine group (176.9+/-41.3 g/m2) was slightly higher than that of patients in the nifedipine group (172.6+/-35.1 g/m2). During M12, LVMI was observed to have decreased both for patients in the rilmenidine group (to 154.8+/-40.2 g/m2, a decrease of 22.1+/-23.3 g/m2, P< 0.001) and for those in the nifedipine group (to 145.6+/-36.4 g/m2, a decrease of 26.9+/-29.5 g/m2, P< 0.001) but the difference between these two groups was not significant (P= 0.5).


CONCLUSIONS
One-year treatment with a daily dosage of 1 or 2 mg rilmenidine achieves a significant reduction of left ventricular mass, which is not statistically different than that occurring with a daily dosage of 40 mg of slow-release nifedipine.
Sadowski
Z
Z
Department of Ischemic Heart Disease, National Institute of Cardiology, Warsaw, Poland.
Szwed
H
H
Kuch-Wocial
A
A
Kubasik
A
A
Januszewicz
W
W
Krupa-Wojciechowska
B
B
Polak
G
G
Stejfa
M
M
Dvorak
I
I
Balazovjech
I
I
Dubai
G
G
Simon
K
K
D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D003971:Diastole; D004311:Double-Blind Method; D004452:Echocardiography; D015716:Electrocardiography, Ambulatory; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000627:therapeutic use; D010080:Oxazoles / Q000627:therapeutic use*; D000077769:Rilmenidine; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D010080:Oxazoles; D009543:Nifedipine; D000077769:Rilmenidine