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J Pharmacol Sci. 2010;113(4):292-5. Epub 2010 Jul 27.

New approaches to blockade of the renin-angiotensin-aldosterone system: evidence from randomized controlled trials (RCTs) of angiotensin-converting enzyme inhibitors and angiotensin II-receptor blockers--questions remain unsolved.

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Department of Clinical Pharmacology & Therapeutics, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.


Recent randomized controlled trials showed that blockade of the renin-angiotensin system (RAS) by angiotensin-converting enzyme (ACE) inhibitors and angiotensin II-receptor blockers (ARBs) reduced cardiovascular and renal events. These drugs are widely used in the management of cardiovascular and renal diseases. Results from Randomized Controlled Trials (RCTs) so far, however, also raise several questions to be addressed. It should be noted that the residual event rate in the treatment arm in outcome studies that have employed ACE inhibitors or ARBs remains high. Such insufficient efficacy of RAS inhibition may result from the fact that neither ACE inhibitors nor ARBs completely suppress activity of RAS. Since then effort has been made to determine whether the dual blockade of RAS could provide further improvement in cardiovascular and renal outcome. This review extracts unsolved questions in the treatment with RAS inhibitors from outcome studies and discusses them from the clinical pharmacological point of view.

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