Are Diuretics a Clandestine Risk Factor for Patients With Treatment-Resistant Hypertension?

The control of blood pressure in patients with treatment-resistant hypertension is paramount and requires the use of thiazide or loop diuretics to enhance renal salt excretion and reduce expanded body fluid volumes. However, the use of diuretics in patients with treatment-resistant hypertension without suppressing the production of aldosterone and MR (mineralocorticosteroid receptor) activation and signaling may not be sufficient to prevent the development of heart failure and excessive cardiovascular mortality and the progression of chronic kidney disease. This review examines the evidence that diuretic therapy for treatment-resistant hypertension may constitute a risk factor for preventable cardiovascular and renal disease progression that is concealed by the strong offsetting effects of a fall in blood pressure. To gain the full benefits of diuretic therapy in treatment-resistant hypertension may require the earlier prescription of MR antagonists coincident with diuretics rather than delaying their use to fourth-line agents in those who remain uncontrolled. This will require testing in appropriate clinical trials.