AT1-receptor blockers in hypertension and heart failure: clinical experience and future directions.

In various manifestations of cardiovascular disease, blockade of the renin–angiotensin system by angiotensin converting enzyme (ACE) inhibitors has been shown to prevent or delay disease progression effectively and improve prognosis in terms of mortality and morbidity. Angiotensin type 1-receptor (AT1-receptor) blockers, on the other hand, are used for more specific and efficacious blockade of the renin–angiotensin system, by blocking the deleterious effects of the activated renin–angiotensin system selectively and effectively at the receptor level. The introduction of this pharmacological principle is in line with the general development of more refined drug interaction with biological systems. Several AT1receptor blockers are available, and those currently accessible for clinical use are listed in Table 1. Pharmacological differences exist between AT1receptor blockers (Table 2), but no definite data indicate that these differences have clinical relevance. Indeed, according to the American Food and Drug Administration, there are no differences between AT1-receptor blockers in terms of blood pressure lowering. However, recent results from studies in patients with heart failure using different AT1-receptor blockers are conflicting, raising the question of whether clinically relevant differences might exist. Losartan, first registered in Sweden in September 1994 for use in hypertension, is the first and, so far, the most extensively documented substance in this group. In many countries, several AT1-receptor blockers have since become available for clinical use, including for the treatment of heart failure (Table 1). Clinical experience in general practice is extensive and AT1-receptor blockers have been prescribed to several million patients