Endothelin antagonism: a new era for resistant hypertension?

Hypertension, defined as a blood pressure (BP) above which treatment provides more benefit than harm, is the leading cause of morbidity and mortality worldwide and is strongly associated with the development of a range of diseases, including cerebrovascular, chronic kidney, and coronary disease. Between 1990 and 2019 the global prevalence of hypertension doubled and it is now estimated to affect ~1 in 4 adults worldwide.1 Despite an extensive therapeutic armamentarium, only 1 in 5 individuals with hypertension achieves adequate BP control..2 The reasons for this are multifactorial and include therapeutic inertia partly as a consequence of physicians doubting the accuracy of office BP measures,3 and poor medication adherence.4 However, there is a particularly high-risk group of patients with treatment-resistant hypertension (TRH) who, despite lifestyle measures and adherence to maximally tolerated doses of three or more different classes of antihypertensive including a diuretic, continue to have uncontrolled BP.