New therapeutic agents in the management of hypertension: angiotensin II-receptor antagonists and renin inhibitors

OBJECTIVE: To review the chemistry, pharmacokinetics, and clinical trials of two new classes of antihypertensive drugs, angiotensin II-receptor antagonists and renin inhibitors. DATA SOURCES: Primary literature on angiotensin II-receptor antagonists and renin inhibitors was identified through a comprehensive medical literature search from 1961 through 1993. This search included journal articles, abstracts, and reports of both animal and human research published in the English language. Indexing terms included renin-angiotensin aldosterone system, renin inhibitors, angiotensin II antagonists, DuP 753, losartan, MK954, A-64662, and Ro 42-5892. STUDY SELECTIONS: Emphasis was placed on clinical and pharmacokinetic studies in humans for drugs that are currently in Phase I-III research protocols in the US. DATA EXTRACTION: All available data from human studies were reviewed. DATA SYNTHESIS: Angiotensin II-receptor antagonists and renin inhibitors may be effective antihypertensives with few adverse effects noted in the small studies completed. Their potential advantage over angiotensin-converting enzyme (ACE) inhibitors includes a possible smaller adverse effect profile. In the past, the clinical utility of angiotensin II-receptor antagonists and renin inhibitors has been limited because of poor oral bioavailability, although newer agents are more readily bioavailable. CONCLUSIONS: Angiotensin II-receptor antagonists and renin inhibitors may be the next new classes of antihypertensives marketed. However, definitive conclusions about their roles in the management of hypertension are not possible until larger clinical trials assessing their efficacy and safety and comparing them with ACE inhibitors are completed.