Emerging concepts for patients with treatment-resistant hypertension

Treatment-resistant hypertension (TRH) is defined as elevated blood pressure despite treatment with three properly dosed antihypertensive drugs, and is associated with adverse cardiovascular and renal outcomes and increased mortality. Treatment of patients with TRH focuses on maximizing the doses of antihypertensive drugs and adding drugs with complementary mechanisms of action, including a combination of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, calcium channel blockers, and thiazide-like diuretics. Randomized clinical trials have demonstrated the efficacy of the mineralocorticoid receptor antagonist spironolactone as a fourth-line therapy for patients with TRH. Other pharmacologic considerations include adding α-blockers, combined α–β-blockers, centrally acting α-agonists, or direct vasodilators. However, a small, but important subset of patients remain hypertensive despite combination regimens with multiple antihypertensive drugs, underscoring the need for novel blood pressure-lowering therapies. Over recent years, alternative approaches for treating TRH have emerged, including agonists of natriuretic peptides, endothelin-receptor antagonists, and additional vasoactive drugs. Lastly, device-based interventions, such as renal denervation or carotid baroreflex activation, may supplement drug therapy for these patients. This review summarizes current knowledge on the management of TRH, with focus on novel therapeutic strategies designed to achieve optimal blood pressure control.