DORADO: Opportunity Postponed

Abstract

Treatment-resistant hypertension (TRH) describes a situation where blood pressure (BP) remains above target in spite of the concurrent use of 3 antihypertensive agents of different classes, with 1 of the agents a diuretic, and all ideally given at an optimized dose. TRH is a common clinical problem, perhaps occurring in 20% to 30% of participants in hypertension trials, and is likely to become increasingly common in the future because BP targets are reducing, and older age and obesity are 2 of the strongest risk factors for its occurrence.1 A number of interventions have been shown to reduce BP substantially in patients with TRH, and, with its growing prevalence and the excellent cost-effectiveness of current first-line treatments, it is increasingly becoming a valuable indication in its own right for newly licensed medicines. One such intervention that has shown promise in this indication is the use of endothelin receptor antagonists (ETRAs). In a major study (DORADO) published last year,2 the ETRA darusentan, at doses of 50, 100, and 300 mg daily, was studied in 379 patients with TRH using a randomized, double-blind, placebo-controlled design. Comorbidities in these patients included type 2 diabetes mellitus and chronic kidney disease. Reduction in the coprimary end points of seated systolic and diastolic BPs at week 14 of treatment were 17/10, 18/10, and 18/11 mm Hg with increasing doses of darusentan but significantly less with placebo at only 9/5 …