Indications for and utilization of angiotensin receptor II blockers in patients at high cardiovascular risk

Abstract

The worldwide burden of cardiovascular disease is growing. In addition to lifestyle changes, pharmacologic agents that can modify cardiovascular disease processes have the potential to reduce cardiovascular events. Antihypertensive agents are widely used to reduce the risk of cardiovascular events partly beyond that of blood pressure-lowering. In particular, the angiotensin II receptor blockers (ARBs), which antagonize the vasoconstrictive and proinflammatory/pro-proliferative effects of angiotensin II, have been shown to be cardio vascularly protective and well tolerated. Although the eight currently available ARBs are all indicated for the treatment of hypertension, they have partly different pharmacology, and their pharmacokinetic and pharmacodynamic properties differ. ARB trials for reduction of cardiovascular risk can be broadly categorized into those in patients with/without hypertension and additional risk factors, in patients with evidence of cardiovascular disease, and in patients with severe cardiovascular disease, such as heart failure. These differences have led to their indications in different populations. For hypertensive patients with left ventricular hypertrophy, losartan was approved to have an indication for stroke prevention, while for most patients at high-risk for cardiovascular events, telmisartan is an appropriate therapy because it has a cardiovascular preventive indication. Other ARBs are indicated for narrowly defined high-risk patients, such as those with hypertension or heart failure. Although in one analysis a possible link between ARBs and increased risks of cancer has surfaced, several meta-analyses, using the most comprehensive data available, have found no link between any ARB, or the class as a whole, and cancer. Most recently, the US Food and Drug Administration completed a review of the potential risk of cancer and concluded that treatment with an ARB medication does not increase the risk of developing cancer. This review discusses the clinical evidence supporting the different indications for each of the ARBs and the outstanding safety of this drug class.

Aliskiren – an antihypertensive renin inhibitor in the treatment of patients with chronic kidney disease

“…As the blockade of the RAAS system with ACE inhibitors or ARBs has been proven to be a powerful tool for treating hypertension and heart failure [10], and slow or prevent progression of chronic proteinuric nephropathies [14], the research on drugs affecting the RAAS system continues. Aliskiren is the first orally bioavailable direct renin inhibitor approved for the treatment of hypertension [16].…”

“…In kidney, ANG II basically induces vasoconstriction in the efferent glomerular arteries leading to glomerular hypertrophy [8] and vasoconstriction of glomerular capillaries, which affects the glomerular filtration rate [9]. ANG II has multiple biological effects in addition to causing vasoconstriction of arteries and modulating blood pressure, including acting as a proinflammatory mediator at all stages of the cardiovascular and renal disease [10]. The actions of ANG II are mediated by AT 1 and AT 2 receptors, which are seven transmembrane glycoproteins with 30% sequence similarity [11].…”

“…The actions of ANG II are mediated by AT 1 and AT 2 receptors, which are seven transmembrane glycoproteins with 30% sequence similarity [11]. ANG II induces acute vasoconstriction by binding mainly to AT 1 receptors while AT 2 receptors activation is thought to have the opposite effects of those mediated by the AT 1 receptors, which are beneficial to the cardiovascular system and help protect target organs from damage [10]. By blocking the formation of ANG II in blood, ACE inhibitors significantly lower systemic vascular resistance, lower blood pressure, and improve cardiac function [12].…”

“…By blocking the formation of ANG II in blood, ACE inhibitors significantly lower systemic vascular resistance, lower blood pressure, and improve cardiac function [12]. Apart from blocking the actions of ANG II that are mediated by AT 1 receptors, angiotensin II receptor blockers (ARBs) may induce endorgan protection by leaving AT 2 receptors free to be activated by ANG II [10]. ACE inhibitors and ARBs are routinely used drugs in the treatment of hypertension and heart failure [10,12].…”

“…Apart from blocking the actions of ANG II that are mediated by AT 1 receptors, angiotensin II receptor blockers (ARBs) may induce endorgan protection by leaving AT 2 receptors free to be activated by ANG II [10]. ACE inhibitors and ARBs are routinely used drugs in the treatment of hypertension and heart failure [10,12]. Furthermore, these drugs are also effective in reducing proteinuria and may delay or even prevent end-stage renal disease (ESRD) in both diabetic and non-diabetic proteinuric CKD [13].…”