ANGIOTENSIN-II RECEPTOR ANTAGONISTS - THE PROTOTYPE LOSARTAN

OBJECTIVE: TO describe a new class of antihypertensive agents, the ang iotensin II receptor antagonists, with emphasis on the prototype losar tan. Pharmacokinetic data and clinical trials are reviewed, as well as adverse reactions, drug interactions, and dosing guidelines. DATA SOU RCES: A MEDLINE search of English-language literature published from 1 966 through 1995 was performed. In addition, Merck and Co. provided bi bliographic data on file for losartan. STUDY SELECTION: Emphasis was p laced on clinical and pharmacokinetic studies in humans. Controlled, d ouble-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 compa rative clinical trials, losartan appears to have antihypertensive effi cacy similar to that of the angiotensin-converting enzyme (ACE) inhibi tors. Losartan is well tolerated, with an adverse effect profile simil ar to that of placebo and a reduced incidence of cough versus that wit h ACE inhibitors. A combination product consisting of losartan 50 mg a nd hydrochlorothiazide 12.5 mg has also received approval for the trea tment of hypertension. The combination product is not indicated for in itial therapy, but is recommended for patients who do not respond adeq uately to losartan monotherapy. The angiotensin II receptor antagonist s 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 a pproval for use in the US, appears to be an effective new antihyperten sive agent with an adverse effect profile similar to that of placebo. Losartan may be an alternative for patients who cannot tolerate ACE in hibitors. However, the effect of losartan on mortality remains to be e valuated. The role of the angiotensin II receptor antagonists in areas such as ventricular hyper-trophy, renal function, and heart failure h as yet to be determined.