Review Article

Rationale for Combination Therapy in Hypertension Management: Focus on Angiotensin Receptor Blockers and Thiazide Diuretics

Authors: David T. Nash, MD

Abstract

Despite recognition that hypertension is a major risk factor for cardiovascular events and mortality, blood pressure control rates remain low in the US population. Reflecting clinical trial results, hypertension management guidelines assert the clinical benefit of achieving current blood pressure goals and indicate that most patients will require 2 or more drugs to reach goal. Well-designed drug combinations counter hypertension via complementary mechanisms that increase antihypertensive efficacy, potentially with lower rates of adverse events than higher dose monotherapy regimens. Lower adverse event rates, in turn, may contribute to greater adherence with treatment. The combination of a low-dose diuretic with agents that block the effects of the renin-angiotensin system (RAS), such as angiotensin receptor blockers, has been found in numerous clinical trials to be highly effective for lowering blood pressure in patients with uncomplicated as well as high-risk hypertension, with a comparable favorable side effect profile compared with monotherapy. Moreover, agents that block the RAS are associated with a lower risk of new-onset diabetes mellitus than other antihypertensive classes. Complementary combinations of antihypertensive agents provide an efficient and effective approach to hypertension management.


Key Points


* Results of large-scale clinical trials indicate that most patients, particularly those at high risk for cardiovascular events require 2 or more antihypertensive agents to reach blood pressure goals recommended by current clinical guidelines.


* Because the pathophysiology of hypertension is multifactorial, well-designed combination regimens that target complementary blood pressure-lowering mechanisms provide an effective approach to achieving goals.


* The combination of an angiotensin receptor blocker with a thiazide diuretic provides several advantages for treating essential hypertension as well as patients at high risk for cardiovascular or renal disease events, based on their additive efficacy and lower rate of adverse effects and treatment discontinuations compared with higher dose component monotherapy or other antihypertensive regimens.


* Rates of patient adherence to antihypertensive therapy are higher with angiotensin receptor blockers than other antihypertensive classes in several observational studies.


* Agents that block the renin-angiotensin system also are associated with a lower incidence of new-onset diabetes than other antihypertensive classes or placebo.

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