Angiotensin II antagonists

Abstract

Angiotensin II antagonists (AIIAs) are a new and rapidly growing class of therapeutic agents competing in a 13 billion dollar worldwide antihypertensives market. These agents act by blocking the effects of angiotensin II (AII) at the AT1 receptor. Losartan was the first member of this class, and the safety and efficacy of this molecule in hypertensive patients have led to rapid market acceptance and prompted the development of many additional agents. Losartan has also stimulated scientific research in the area of AII receptor heterogeneity and in characterising the pathologic role of AII. Losartan and other members of this class, such as valsartan, candesartan, irbesartan, and eprosartan, have been approved for hypertension, and losartan has now been approved for heart failure in several countries in Europe. Studies with the other AII antagonists are ongoing for heart failure and renal dysfunction indications. The excellent tolerability of this class of drugs is expected to enhance patient compliance compared to other commonly used agents: this high degree of patient acceptance is likely to result in better control of blood pressure in a higher percentage of patients and a greater reduction in the occurrence of cardiovascular morbid events. AIIAs will largely replace other antihypertensive agents such as diuretics, calcium channel blockers, beta-blockers and ACE inhibitors for the initial treatment of hypertension-related cardiovascular disease in the future. The rapidity of the switch away from current therapeutic agents will depend in large part on health economic factors and the availability of positive end-point data from the large ongoing trials with losartan (LIFE, ELITE II, RENAAL, OPTIMAAL), and other AIIAs (VALUE, VAL-HEFT). The quality of the therapeutic effect of AIIAs with regard to efficacy and safety, and the magnitude of their market potential have combined to fuel an unprecedented international clinical development and marketing effort for this exciting new class of cardiovascular agents.