New Approaches in the Treatment of Hypertension

Abstract

Hypertension is the most common modifiable risk factor for cardiovascular disease and death, and lowering blood pressure with antihypertensive drugs reduces target organ damage and prevents cardiovascular disease outcomes. Despite a plethora of available treatment options, a substantial portion of the hypertensive population has uncontrolled blood pressure. The unmet need of controlling blood pressure in this population may be addressed, in part, by developing new drugs and devices/procedures to treat hypertension and its comorbidities. In this Compendium Review, we discuss new drugs and interventional treatments that are undergoing preclinical or clinical testing for hypertension treatment. New drug classes, eg, inhibitors of vasopeptidases, aldosterone synthase and soluble epoxide hydrolase, agonists of natriuretic peptide A and vasoactive intestinal peptide receptor 2, and a novel mineralocorticoid receptor antagonist are in phase II/III of development, while inhibitors of aminopeptidase A, dopamine β-hydroxylase, and the intestinal Na + /H + exchanger 3, agonists of components of the angiotensin-converting enzyme 2/angiotensin(1–7)/Mas receptor axis and vaccines directed toward angiotensin II and its type 1 receptor are in phase I or preclinical development. The two main interventional approaches, transcatheter renal denervation and baroreflex activation therapy, are used in clinical practice for severe treatment resistant hypertension in some countries. Renal denervation is also being evaluated for treatment of various comorbidities, eg, chronic heart failure, cardiac arrhythmias and chronic renal failure. Novel interventional approaches in early development include carotid body ablation and arteriovenous fistula placement. Importantly, none of these novel drug or device treatments has been shown to prevent cardiovascular disease outcomes or death in hypertensive patients.

The circle of Willis predicts the antihypertensive effects of carotid artery stenting

“…Numerous studies, and indeed many of our current stroke guidelines, have previously emphasized that BP drives end-organ perfusion in the acute setting. 4,14,15 Our study suggests that inadequate intracranial perfusion via high-resistance pial pathways may be an additional factor that increases long-term systemic BP and that these effects are independent of confounders such as diabetes and hyperlipidemia. While secondary causes of hypertension such as renal artery stenosis, excessive fluid or volume status, pheochromocytoma, hypercortisolism, hyperaldosteronism, and lifestyle factors have been previously described, this is, to the best of our knowledge, the first study to specifically explore the interaction of intracranial and extracranial anatomy as a cause of sustained systemic hypertension.…”

“…4,14,15 While the pathogenesis of these two diseases is known to intersect, the pathophysiological mechanism that these diseases share is not well established. Several studies have examined the clinical response that treating carotid artery stenosis had on BP, with most finding a greater reduction of hypertension in stenting group compared with the carotid endarterectomy group.…”

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FOCUS

Neurosurg Focus 42 (4):E18, 2017T he diagnosis and treatment of hypertension and atherosclerotic stenosis of the carotid artery are imperative clinical objectives for preventing stroke, 8,14 and yet the pathophysiological mechanisms linking these two diseases remains incompletely characterized. In addition to the transient carotid artery baroreceptor -mediated hypotension that may complicate carotid artery stent (CAS) placement, 17 stenting has been shown to exert durable reductions in postoperative blood pressure (BP) and requirements for antihypertensive medications.

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Pacemaker‐Mediated Programmable Hypertension Control Therapy

“…These include baroreceptor activation therapy,17, 18, 19 renal denervation,7, 20 arteriovenous shunting,10, 21 carotid body resection or denervation,12, 22 and mechanical stimulation of the baroreceptors 23. Prior review articles have provided overviews and comparisons of these different approaches and will not be repeated here,24, 25 other than to say that treatment of isolated systolic hypertension (ie, patients with office diastolic blood pressure <90 mm Hg), which is characterized by increased vascular stiffness, has proved to be particularly challenging for some of these approaches, with such patients excluded from the recently complete SPYRAL HTN‐OFF MED study 19, 26. It is therefore noteworthy that 78% of patients in the present study had isolated systolic hypertension with an excellent response rate.…”

Introduction to a Compendium on Hypertension

“…This implies that only early therapeutic interventions can successfully normalize the risk, challenging the belief that treatment is highly cost-effective, and should thus be implemented, only when cardiovascular risk is elevated. Finally, Oparil and Schmieder 16 provide an overview of the antihypertensive drugs under current investigation as well as of the 2 main nonpharmacological interventions (renal denervation and baroreceptor stimulation) that have come to attention in the past few years, mentioning in each case available evidence, potential, and limitations.…”