Targeting mechanisms of hypertensive vascular disease with dual calcium channel and renin-angiotensin system blockade

Abstract

Patients with hypertension, particularly those with diabetes mellitus, are at heightened risk for cardiovascular and renal disease. Accumulated evidence indicates that the majority of hypertensive patients at high risk will require more than one antihypertensive agent to reach their blood pressure (BP) target. A reasonable strategy is to use agents with complementary mechanisms of action to enhance BP-lowering efficacy and prevent target organ damage. In experimental models, the combination of a calcium channel blocker (CCB) with an agent that blocks the renin-angiotensin system (RAS), an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker, improves measures of endothelial function, inflammation, ventricular remodelling and renal function to a greater degree than these classes given as monotherapy. In clinical trials, calcium channel/RAS blockade combination therapy has been shown to provide greater BP reductions and improve renal function in patients with diabetic and nondiabetic renal disease earlier and to a greater extent than monotherapy. In addition, dual calcium channel/RAS blockade increases arterial compliance, arterial distensibility and flow-mediated vasodilation. Expanding upon extensive research on the benefits of calcium channel blockade and RAS blockade for the prevention of vascular events and preclinical and clinical trial evidence suggests added effects of combination therapy by targeting the underlying mechanisms of hypertensive vascular disease.