Luis I Juncos and Caputo Joaquin
The renin-angiotensin system (RAS) exerts wide-ranging effects on cardiovascular and kidney function. Oddly, this system that was designed to preserve normal hemodynamics may become harmful in certain clinical situations. For this reason, RAS inhibition is a highly effective therapeutic approach, not only to lower blood pressure but also to reduce kidney and cardiovascular disease morbidity and mortality. In some patients however, these beneficial effects of RAS inhibition are incomplete or absent. For these less than ideal results, several reasons have been proposed; e.g.: angiotensin escape, over production of angiotensin from negative feedback, local tissue RAS, etc. To secure better RAS blocking, some clinicians have proposed increasing the dose of angiotensin converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB’s) beyond the recommended doses or combining two RAS inhibitors. In high-risk patients though, this more intensive RAS inhibition should be undertaken with great precaution, as tissue perfusion may be highly renin-dependent and serious adverse side effects could take place. This issue is yet to be settled as patients with significant proteinuria can be benefitted by intensive RAS inhibition. The purpose of this article is to review the evidences accrued on the use of intensive or dual blocking of RAS. We analyze potential purposes and hazards in the light of actual population data as published in recent trials.
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