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.

Keywords: angiotensin II receptor blocker; cardiometabolic risk; cardiovascular disease; cardiovascular prevention.

Figure 1

Scheme of the renin-angiotensin system. Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blockers; NO, nitric oxide; SNS, sympathetic nervous system; tPA, tissue plasminogen activator; AT₁, angiotensin II type 1 receptor; AT₂, angiotensin II type 2 receptor.