Angiotensin Receptor Blockers Should Be Regarded as First-Line Drugs for Stroke Prevention in Both Primary and Secondary Prevention Settings

“It is a wise man’s part, rather to avoid sickness, than to wish for medicines.” — —Thomas More (1475 to 1535), Utopia Angiotensin II receptor blockers (ARBs) are hypothesized to have superior stroke protection as compared with other antihypertensives based on their moderating effects of the renin–angiotensin–aldosterone system. Activation of the renin–angiotensin–aldosterone system plays an important role in both the pathophysiology of hypertension and atherosclerotic vascular disease. ARB attenuate renin–angiotensin–aldosterone system activation by competitively inhibiting the binding of angiotensin II (Ang II) to AT1 receptors while allowing for unopposed stimulation of the AT2 receptors.1 AT1 blockade interrupts a negative feedback loop leading to a 3- to 5-fold increase in Ang II levels from baseline with hyperstimulation of AT2 receptors. AT2 activation is hypothesized to protect against stroke by recruiting cerebral collateral vessels and enhancing neuronal resistance to anoxia2 and by attenuating prothrombosis, inflammation, and endothelial dysfunction that mediate atherosclerosis.1Analyses of multiple large clinical trials do not, however, support any unique blood pressure-“independent” effects of ARB on stroke prevention. In a meta-analysis of ARB versus any active comparator or placebo by these authors (n=53 318, 11 trials), ARB did …