Hypertension Express Report

Publication date: 2004-12-28

Understanding the Antihypertensive Effect of ACE Inhibitor/Calcium-channel Blocker Combination Therapy

This report was reviewed for medical and scientific accuracy by George L. Bakris, MD, FACP, FAHA, FCP, Professor, Departments of Preventive and Internal Medicine and Director, Hypertension Research Center, Rush University Medical Center, Chicago, Illinois

Introduction

Hypertension is a common condition affecting more than 50 million Americans and approximately 1 billion individuals worldwide.¹ However, despite the availability of numerous antihypertensive therapies and increases in awareness and treatment of hypertension over the last 25 years, approximately two-thirds of patients remain inadequately controlled (have systolic and/or diastolic blood pressures above targets for patients with uncomplicated disease).¹ Moreover, 30% are still unaware they have hypertension.

Excellent clinical trial outcome data demonstrate that lowering blood pressure with several classes of pharmacologic agents, including angiotensin-converting-enzyme (ACE) inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, and thiazide-type diuretics, will all reduce the complications of hypertension.^2-9

Whereas there is some disagreement among published guidelines regarding which agent or agents should be used as first-line therapy, most concur that the majority of patients will require concomitant therapy with 2 or more antihypertensive agents to achieve optimal blood pressure control.¹⁰ According to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), more than two-thirds of hypertensive patients will require therapy with 2 or more agents from different antihypertensive classes to achieve target blood pressure goals.¹ Effective blood pressure control is associated with significant health benefits, including reductions in stroke incidence (35% to 40%), myocardial infarction (20% to 25%), and heart failure (>50%).²

A multitude of combination therapies has been studied for the treatment of hypertension. More specifically, interest in combination ACE inhibitor/calcium-channel blocker therapy has been perpetuated by the complementary mechanisms of action of these 2 classes of antihypertensive drugs.^10,11 Agents from both classes of drugs reduce vascular resistance and promote natriuresis; however, the mechanisms by which they do so are different. Some synergistic effects have been described (eg, antihypertensive effects of ACE inhibitors are enhanced by the negative sodium balance produced by calcium-channel blockers). Furthermore, combination therapy may overcome some of the unwanted effects of monotherapy (eg, ACE inhibitors may blunt the undesirable stimulation of the renin-angiotensin system triggered by calcium-channel blocker activity). Use of the non-dihydropyridine calcium antagonist verapamil in such combinations avoids the undesirable sympathetic activation (reflex tachycardia) that can occur with dihydropyridine calcium antagonists.¹²

There are currently 3 commercially available combinations of ACE inhibitor/calcium-channel blocker therapies for the treatment of hypertension — trandolapril/verapamil extended-release (ER) (Tarka), amlodipine besylate/benazepril hydrochloride (Lotrel), and enalapril maleate/felodipine (Lexxel). Trandolapril/verapamil-ER has been shown to produce significant blood pressure lowering effects and consistent 24-hour blood pressure control with once-daily administration.^10,11,13 This Hypertension Express Report will focus on recent data on the role of combination trandolapril/verapamil-ER therapy in the treatment of hypertension.

Efficacy and Safety of Combination Trandolapril/Verapamil-ER Therapy

Clinical studies have shown that, in patients with mild to moderate essential hypertension, combination therapy with trandolapril and verapamil-ER produces blood pressure lowering effects superior to placebo and superior to those produced by either agent admini