Volume 1, Number 3, September 2000

Effectively targetting the renin-angiotensin-aldosterone system in cardiovascular and renal disease: rationale for using angiotensin II receptor blockers in combination with angiotensin-converting enzyme inhibitors
Marc S Weinberg, Adam J Weinberg, Dion H Zappe

Combining angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACE-I) is a new therapeutic approach to improving outcomes in hypertension, heart failure and renal disease. Evidence suggests that long-term ACE-inhibition results in incomplete renin-angiotensin-aldosterone system (RAAS) blockade, thus potentially reducing its full tissue protective effects. Recent studies have confirmed the importance of using ACE-I at doses higher than the recommended levels for blood pressure (BP) control in cardiovascular disease states where the RAAS is known to be chronically activated. Chronic RAAS activation results in progressive damage to target, end-organ function (e.g. vasculature, kidneys, heart), attributed to BP elevation and haemodynamic changes but also through its local, tissue-based effects (e.g. hypertrophy, fibrosis, remodelling). Combining two RAAS blockers that act at different sites of the renin-angiotensin cascade, rather than increasing the dose of either agent alone, should allow more effective tissue-based RAAS blockade, while sparing maximal doses of medications. A majority of the clinical studies, involving the addition of an ARB to ACE-I therapy, demonstrated additional but small reductions in BP when compared with high-dose monotherapy. The benefits of combining ACE-I and ARB therapies are to provide optimal tissue-RAAS blockade in order to maximally reduce target organ disease. The combined therapy of ARBs and ACE-I allows optimal blockade of the RAAS at relatively lower doses of both agents and is preferable to titrating to higher doses than the ACE-I to some undefined optimal level.

JRAAS 2000;1:217-233.

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