Endothelin antagonist for the treatment of resistant hypertension

Abstract

Introduction: More aggressive lowering of blood pressure (BP) is widely considered an important strategy in reducing cardiovascular morbidity and mortality, yet despite increased awareness and extensive use of combination therapy, recommended BP goals are frequently not achieved. Resistant hypertension is defi ned as the failure to achieve guideline-recommended BP goals in patients who are adherent to an appropriate three-drug regimen including a diuretic. The prevalence of resistant hypertension, probably less than 5% in an unselected hypertensive population, may be as high as 50% in patients followed in specialty referral clinics. Thus additional therapeutic modalities are needed. Endothelin receptor antagonists (ERAs) have been shown to have modest antihypertensive effects in prior studies, particularly in patients with more severe hypertension. Darusentan, a selective endothelin type A receptor ERA, has been effective and well tolerated, and the authors hypothesized that, because it lowers BP by a different mechanism than other classes, it might be useful as add-on therapy in patients with resistant hypertension.