Objective To describe a new class of antihypertensive agents, the angiotensin II receptor antagonists, with emphasis on the prototype losartan. Pharmacokinetic data and clinical trials are reviewed, as well as adverse reactions, drug interactions, and dosing guidelines. Data Sources A MEDLINE search of English-language literature published from 1966 through 1995 was performed. In addition, Merck and Co. provided bibliographic data on file for losartan. Study Selection Emphasis was placed on clinical and pharmacokinetic studies in humans. Controlled, double-blind studies were evaluated to assess the efficacy and adverse effect profile of losartan. Data Synthesis Losartan is a nonpeptide, competitive antagonist of the type 1 angiotensin II receptor. In comparative clinical trials, losartan appears to have antihypertensive efficacy similar to that of the angiotensin-converting enzyme (ACE) inhibitors. Losartan is well tolerated, with an adverse effect profile similar to that of placebo and a reduced incidence of cough versus that with ACE inhibitors. A combination product consisting of losartan 50 mg and hydrochlorothiazide 12.5 mg has also received approval for the treatment of hypertension. The combination product is not indicated for initial therapy, but is recommended for patients who do not respond adequately to losartan monotherapy. The angiotensin II receptor antagonists are also being investigated for beneficial effects in patients with ventricular hypertrophy, renal disease, and heart failure. Conclusions Losartan, the first angiotensin II receptor antagonist to receive approval for use in the US, appears to be an effective new antihypertensive agent with an adverse effect profile similar to that of placebo. Losartan may be an alternative for patients who cannot tolerate ACE inhibitors. However, the effect of losartan on mortality remains to be evaluated. The role of the angiotensin II receptor antagonists in areas such as ventricular hypertrophy, renal function, and heart failure has yet to be determined.
Maximally Recommended Doses of Angiotensin-Converting Enzyme (ACE) Inhibitors Do Not Completely Prevent ACE-Mediated Formation of Angiotensin II in Chronic Heart Failure
