INHIBITION OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM IN HEART-FAILURE - NEW INSIGHTS FROM BASIC CLINICAL RESEARCH

It is sobering to recall that, despite much basic research and many sm all and large clinical trials, we still do not know how angiotensin-co nverting enzyme inhibitors work. This is true both in terms of their f undamental mode of action at a cellular level as well as in the patien t in the clinical setting. New pharmaceutical compounds such as renin inhibitors, angiotensin II receptor antagonists and aldosterone antago nists are bringing new insights not only into the importance of differ ent components of the renin-angiotensin-aldosterone system in heart fa ilure but also into the mode of action of angiotensin-converting enzym e inhibitors. This manuscript also provides a brief update on the orga nization of the renin-angiotensin-aldosterone system and other angiote nsin-II-forming pathways with special relevance to heart failure. Data on the potential relevance of genetic polymorphisms of the renin-angi otensin-aldosterone system are discussed. Possibly the single most imp ortant observation in clinical cardiovascular medicine in 1995 was the reporting of a highly significant interaction between angiotensin-con verting enzyme inhibitors and aspirin on mortality in patients with ve ntricular dysfunction with or without heart failure. This has called i nto question the safety of aspirin use in heart failure.