Global efficacy and tolerability of losartan, an angiotensin II subtype 1-receptor antagonist, in the treatment of hypertension.
Losartan is the first drug of a new therapeutic class, the angiotensin II (A II)-receptor antagonists, to be clinically studied and become available for the management of hypertension. Clinical experience with losartan from worldwide, double-blind, controlled studies has been obtained in more than 2900 hypertensive patients treated with losartan alone or in combination with hydrochlorothiazide, with 1700 patients receiving treatment for more than a year. The efficacy of losartan was evaluated in the young and old, in different degrees of hypertension, in blacks and nonblacks, and in patients with renal impairment. Tolerability parameters were assessed by subgroup as well. In dose-ranging studies, 50 mg once daily has generally been shown to produce near maximum effects and a dose of 100 mg does not produce additional effects. The efficacy of losartan (50 to 100 mg once daily) has been compared to atenolol (50 to 100 mg once daily), felodipine ER (5 to 10 mg once daily), and enalapril (20 mg once daily). The blood pressure-lowering effect of losartan was comparable to felodipine, enalapril, and atenolol. The efficacy of losartan was demonstrated using ambulatory blood pressure monitoring, which showed that losartan 50 mg once daily produced gradual reduction in blood pressure, providing 24-h control without affecting the body's circadian rhythm. In subgroups of study populations, no differences in efficacy were noted with respect to age, gender and the severity of hypertension. No initial dosage adjustment is necessary in the elderly and patients with renal impairment (even those on dialysis). Among blacks, the mean response of losartan was lower, which is not surprising given the lesser activation of the renin-angiotensin system in this population. A subgroup safety and tolerability analysis confirmed that there were no important differences in adverse events when assessed by age, race, or gender. The data obtained from controlled clinical trials conducted with losartan, the first A II-receptor antagonist, has shown that a single daily 50-mg dose provides adequate 24-h control of blood pressure in most patients with comparable efficacy to other classes and is well tolerated.
Centre Hospitalier, Universitaire de Grenoble, Hôpital Michallon, France.
J M
JM
Mallion
A I
AI
Goldberg
D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D019808:Losartan; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D013777:Tetrazoles / Q000009:adverse effects* / Q000627:therapeutic use
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D019808:Losartan