Combination therapy for the clinical management of hypertension

Abstract

Effective treatment of hypertension represents a key strategy for preventing major cardiovascular events, including myocardial infarction, stroke, congestive heart failure and cardiovascular death. In spite of these well-established concepts, hypertension remains poorly controlled, worldwide. To reduce this gap and to improve blood pressure control at general population level, the use of rational, synergistic and integrated pharmacological strategies have been proposed over the last few years. Indeed, a more extensive use of dual or triple combination therapy, particularly in fixed formulation, is progressively emerging as a cornerstone of a more effective treatment of hypertension in clinical practice. Among different combination therapies currently available for the clinical management of hypertension, those based on the association of drugs inhibiting the renin-angiotensin system, renal tubular reabsorption of electrolytes and transmembrane influx of calcium ions, both in dual- and in triple-fixed combination formulations, have been demonstrated to be very effective in lowering both systolic and diastolic, clinic as well as 24-h ambulatory blood pressure levels with a good tolerability and safety profile. In the present chapter, we provide a systematic and updated overview of the evidence supporting the use of combination therapies with different classes of antihypertensive drugs, with a particular focus on those based on drugs inhibiting the renin-angiotensin system (e.g. angiotensin-converting enzyme inhibitors, angiotensin AT1 receptor blockers), reabsorption of sodium chloride and water (e.g. thiazide diuretics) and calcium channels (e.g. amlodipine). In addition, we review the currently available clinical data addressing the effects of combination therapies on adherence and persistence on prescribed antihypertensive medications compared to monotherapies, as well as safety and tolerability profile of such different treatment strategies.