Aldosterone blockade over and above ACE-inhibitors in patients with coronary artery disease but without heart failure.
Recent evidence points to a role for the renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of atherosclerosis and its complications, including acute angina pectoris. Two large trials in heart failure have clearly demonstrated that blocking aldosterone improves mortality and that this benefit occurs over and above standard therapy with angiotensin-converting enzyme (ACE) inhibitors. The question that naturally arises from these landmark studies is whether aldosterone blockade would produce the same benefits in patients with coronary artery disease (CAD) but no heart failure. There are three reasons to believe this might be the case. Firstly, angiotensin II (Ang II) and aldosterone produce similar biological effects and Ang II withdrawal has been shown to benefit patients with angina; aldosterone blockade may therefore follow in the footsteps of ACE inhibitors, as it did in heart failure, and produce benefits in vascular patients without heart failure. Secondly, one of the main mechanisms which is thought to be responsible for the benefit of aldosterone blockade in the Randomised ALdactone Evaluation Study (RALES) and Eplerenone Post-AMI Heart Failure Survival Study (EPHESUS), is that it improves endothelial/vascular function and endothelial/vascular dysfunction is the fundamental abnormality in angina pectoris. Finally, aldosterone blockade has been shown to reduce atherosclerosis in animal studies of atherosclerosis without heart failure, which are analogous to CAD patients.
Shah
Nimit C
NC
Department of Medicine and Therapeutics, Ninewells Hospital, Dundee, UK. n.shah@dundee.ac.uk
Pringle
Stuart
S
Struthers
Allan
A
D000450:Aldosterone / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002986:Clinical Trials as Topic; D003324:Coronary Artery Disease / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D006333:Heart Failure; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D013148:Spironolactone / Q000494:pharmacology / Q000627:therapeutic use
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone