DERA Class for Managing Resistant Hypertension

Endothelin Antagonists - A New Treatment Option

Endothelin is one of the most potent vasoconstrictors, and while there has long been interest in antagonizing the endothelin system, finding a safe, predictable, and effective drug has been challenging. A recently approved dual endothelin antagonist that blocks both ETA and ETB receptors now provides blood pressure reduction in a safe and well-tolerated manner, representing the first new class of antihypertensives in decades. This mechanism complements existing therapies by directly addressing the vasoconstriction common in resistant hypertension patients, enhancing blood pressure reduction when added to background therapy.

Aprocitentan, this dual endothelin antagonist, was studied in clinical trials showing effective and consistent blood pressure reduction on top of background three-drug therapy for resistant hypertension. Since becoming available, it has been used as a fourth or fifth medication with results mirroring clinical trials. It has found a unique position for patients with chronic kidney disease who have more limited treatment options, showing efficacy and good tolerability in this population. The main side effect to monitor is leg swelling, which is often mild and can be treated with diuretics. While contraindicated in pregnancy due to teratogenicity, it represents an important new class for resistant hypertension treatment.

Having an entirely new antihypertensive drug class is particularly valuable for patients who have tried most available medications without success due to tolerability issues or perceived ineffectiveness. The novel mechanism of action complements existing treatments and provides a new option for difficult cases, especially patients with chronic kidney disease or those who haven't tolerated other antihypertensive classes. This expands the therapeutic arsenal for treating resistant hypertension cases that previously had limited options.