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Activation of the renin–angiotensin–aldosterone system (RAAS) has been shown to play an important role in cardiac and vascular injury and, conversely, inhibition and/or blockade of this system reduces cardiovascular mortality and morbidity across a wide spectrum of cardiovascular diseases. There remains, however, controversy as to how best to negate the adverse effects of RAAS activation. The results of the ONTARGET1 and TRANSCEND2 studies in patients with high-risk vascular disease, as well as a number of recent meta-analyses of randomised trials comparing the efficacy and safety of angiotensin converting enzyme inhibitors (ACEIs) with angiotensin receptor blocking agents (ARBs) and their combination in patients with heart failure (HF), hypertension, and chronic kidney disease, have focused attention on the RAAS and have provided some further insight into the most effective strategy to prevent the adverse effects of RAAS activation. These insights may, however, need to be modified as the results of new strategies to block/inhibit the RAAS become available. Furthermore, the question as to how best to inhibit/block the RAAS may be disease-specific. It should also be emphasised that despite over two decades of intensive preclinical and clinical investigation our understanding of the RAAS, the consequences of its activation and the most effective strategy to prevent its activation remain incomplete.
COMPARISON OF AN ACEI WITH AN ARB
The HOPE3 and EUROPA4 studies demonstrated the effectiveness of ACEIs ramipril and perindopril in reducing cardiovascular risk in patients with high-risk vascular disease without evidence of clinical HF. The results of PEACE5 examining the ACEI trandolapril and QUIET6 examining quinapril, although less convincing, are compatible with those of HOPE3 and EUROPA.4 While the results of HOPE3 and EUROPA4 have led to an indication for the use of ACEIs in patients with high-risk vascular disease there remains some controversy as to whether their effectiveness …