RAAS inhibition--a practice of medical progress.

The therapeutic utility of inhibiting the RAAS remains one of the major therapeutic successes in cardiovascular medicine over the past decades (1). The angiotensin-converting enzyme (ACE) inhibitors, when first introduced in 1980ies, were indicated only for treatment of refractory hypertension. Since then, they have been shown to reduce morbidity or mortality in hypertension, congestive heart failure, myocardial infarction, diabetes mellitus, chronic renal insufficiency, and atherosclerotic cardiovascular disease (1). These conditions were also targeted by the angiotensin receptor blockers (ARBs), and this class of drugs proved to be beneficial in cardiovascular, renal and metabolic disease as well. As a result of extensive research over the years, it was demonstrated that the pathologies underlying the target organ damage in these conditions were at least partly linked to the reninangiotensin-aldosterone system (RAAS). The end product, angiotensin II is involved in development of structural damage causing endothelial dysfunction, altered renal hemodynamics, as well as vascular and cardiac hypertrophy. Initially the ACE inhibitors and later the ARBs were shown to attenuate or prevent such expressions of target organ damage, an effect that could be translated into improved patient outcomes to the benefit of the individual. The beneficial clinical effects of ACE inhibitors or ARBs which were demonstrated in a number of classical outcome trials, include prevention of myocardial infarction (fatal and nonfatal), re-infarction, angina, stroke, end-stage renal disease, as well as reduction of morbidity and mortality associated with heart failure. In addition to this, these classes of drugs were shown to be generally well tolerated and have few contraindications (2,3). A large number of landmark trials during the past decades have clearly confirmed the benefits of ACE inhibitor or ARB therapy in patients’ cardiovascular and renal disease. Despite the strongly favourable clinical evidence and recent guideline recommendations, RAAS inhibition remains underused in the everyday clinic. When using an ACE inhibitor or an AT1 antagonist, combination with a low dose diuretic is often very attractive when choosing combination therapy. There is increasing evidence that such combination therapies should be utilized more for the initial treatment of hypertensive patients. The collective evidence from major clinical trials in the elderly, diabetics, stroke patients, and other multiple risk patient groups all indicate that combination therapy is necessary to control blood pressure in a reasonable proportion of patients. Although most recent guidelines acknowledge the value of combination therapy, this remains a difficult issue to implement in practice. Several combination therapies such as an ACE inhibitor or an ARB and a diuretic, or an ACE inhibitor or ARB with a calcium antagonist have been shown to be effective in patients who do not respond to monotherapy alone (2,3). This Therapeutic Issue of Blood Pressure, outlines the usefulness of ACE inhibition or ARB alone or in combination with low dose diuretics. Leonetti and coworkers (4) find a high rate of normalisation of blood pressure in mild to moderate hypertension with zofenopril as well as candesartan, supporting the use of these therapies in the first line management of hypertensive patients. Furthermore, the work of Parati and coworkers (5) as well as Abst and coworkers (6) both add important information supporting the utility of RAAS inhibition, i.e. zofenopril or valsartan, and a thiazide diuretic in the management of hypertensive patients not controlled on monotherapy alone. Clearly, if we are to improve the proportion of hypertensive patients reaching desirable blood pressure targets, individualization of antihypertensive therapy will remain an essential issue. Indeed, Blood Pressure. 2006; 15(Suppl 1): 5–6