REVIEW Angiotensin-II receptor blockers: benefits beyond blood pressure reduction? M Volpe 1 , LM Ruilope 2 , GT McInnes 3 , B Waeber 4 and MA Weber 5 1 Division of Cardiology, II Faculty of Medicine, University of Rome ‘La Sapienza’, Sant’Andrea Hospital, Rome, and IRCCS Neuromed—Pozzilli (IS), Italy; 2 Hypertension Unit, Hospital 12 de Octubre, Madrid, Spain; 3 University of Glasgow, Glasgow, UK; 4 Lausanne University, Lausanne, Switzerland; 5 State University of New York, Brooklyn, NY, USA Effective treatment of hypertension is essential to reduce the risk of renal and cardiovascular (CV) morbidity. The risks associated with hypertension are modulated by the presence of other factors. This has prompted the quest for agents that have benefits beyond blood pressure (BP) lowering. The angiotensin II receptor blocker (ARB) class of antihypertensive agents represents an important addition to the thera- peutic options for elevated BP. Their ability to control BP is equivalent to existing therapies and there is a considerable and mounting evidence-base for their ability to reduce hypertension-associated target organ damage and comorbidities. Studies show that ARBs have clinical benefits across the spectrum of disease severity. In particular, recent large studies have demon- strated that these benefits extend to patients with conditions predisposing to CV events, such as diabetes, left ventricular hypertrophy and microalbuminuria, and where risk factors coexist. Data from these studies suggest that the CV protective effects of ARBs are at least, in part, independent from the BP lowering action. In addition, ARBs are extremely well tolerated, and strong evidence suggests that compliance with therapy — a key factor in achieving adequate BP control — with ARBs is higher than with other antihypertensive agents. Furthermore, flexible dosing and good tolerability profile mean that, where necessary, ARBs can be combined with other classes of antihypertensive agents to achieve adequate BP control and reduce the risk of hypertension-associated morbidity. Journal of Human Hypertension (2005) 19, 331–339. doi:10.1038/sj.jhh.1001831 Published online 3 March 2005 Keywords: angiotensin II receptor blockers; antihypertensive therapy; blood pressure; cardiovascular risk Introduction Elevated blood pressure (BP) is clearly and con- tinuously related with cardiovascular (CV) morbid- ity and mortality. A recent meta-analysis has assessed the age-specific relevance of BP to cause- specific mortality. The study analysed information derived from about one million adults with no evidence of previous vascular disease. 1 The inves- tigators found that throughout middle and old age, BP is strongly and directly related to vascular and overall mortality. Furthermore, there was no evidence of a threshold down to a BP of at least 115/75 mmHg. Treatment of hypertension can prolong life, pre- vent or delay the development of heart failure and nephrosclerosis, and reduce the incidence of cor- onary events and stroke. 2 There is a direct relation- ship between the reduction in BP attained and the prognosis for hypertensive patients. Even small reductions in BP are associated with large reduc- tions in CV risk, especially in hypertensive patients with additional CV risk factors such as diabetes. 3 However, there remains a divergence in survival rates between treated hypertensive and nonhyper- tensive men of similar age. 4 This poorer prognosis, even in the presence of active antihypertensive therapy, was observed in patients who were mainly treated with diuretics and b-blockers and followed for up to 23 years. 4 Many factors, including the frequent, concomitant presence of risk factors including diabetes, late initiation of antihypertensive therapy and inade- quate control of BP could account for the poorer prognosis observed in the hypertensive population. In particular, elevated levels of BP are associated with progressive target organ damage, which a late initiation of therapy cannot reverse. The different classes of antihypertensive drugs may have different capacities for organ protection. In particular, those Received 11 October 2004; revised 5 December 2004; accepted 8 December 2004; published online 3 March 2005 Correspondence: Dr M Volpe, Division of Cardiology, II Faculty of Medicine, University ‘La Sapienza’ of Rome, Sant’Andrea Hospital, Via di Grottarossa, 1035-39, 00189 Rome, Italy. E-mail: volpema@uniroma1.it Journal of Human Hypertension (2005) 19, 331–339 & 2005 Nature Publishing Group All rights reserved 0950-9240/05 $30.00 www.nature.com/jhh