New and developing pharmacotherapies for hypertension

ABSTRACT

Introduction

Despite the significant contribution of hypertension to the global burden of disease, disease control remains poor worldwide. Considering this unmet clinical need, several new antihypertensive drugs with novel mechanisms of action are under development.

Areas covered

The present review summarizes the recent advances in the development of emerging pharmacological agents for the management of hypertension. The latest technological innovations in the design of optimized formulations of available antihypertensive drugs and the potential role of the modification of intestinal microbiota to improve blood pressure (BP) control are also covered.

Expert opinion

Significant efforts have been made to develop new antihypertensive agents with novel actions that target the main mechanisms involved in resistant hypertension. Sacubitril/valsartan may emerge as a potential first-line drug due to its superiority over renin angiotensin system inhibitors, and SGLT2 inhibitors can reduce BP in difficult-to-control hypertensive patients with type 2 diabetes. In addition, firibastat and aprocitentan may expand the therapeutic options for resistant hypertension by novel mechanism of actions. Since gut dysbiosis not only leads to hypertension but also causes direct target organ damage, prebiotics and probiotics could represent a potential strategy to prevent or reduce the development of hypertension and to contribute to BP control.

KEYWORDS:

• Resistant hypertension
• sacubitril/valsartan
• aprocitentan
• SGLT2 inhibitors
• firibastat
• microbiota
• novel drug delivery systems

Article highlights

• Although there are many effective options to treat hypertension with a good tolerability profile, the development of new antihypertensive drugs with novel mechanisms of action may eventually help to control high blood pressure.

• Sacubitril/valsartan emerges as a new antihypertensive combination due to its greater BP lowering efficacy when compared with ARBs.

• Firibastat may constitute a potential alternative therapy in the management of high-risk patients with difficult-to-treat or resistant hypertension in whom monotherapy with blockers of the systemic RAS is poorly effective.

• The BP lowering effect of esaxerenone was established in key clinical trials including patients with essential hypertension, diabetic nephropathy, hypertension due to primary aldosteronism, and hypertension with type 2 diabetes and albuminuria or moderate renal impairment.

• Aprocitentan represents an oral non-selective ET-1 receptor antagonist with promising results for the management of arterial hypertension in phase 2 clinical trials.

• Novel drug delivery systems can potentially improve blood pressure control in hypertensive patients due to their ability to offer long-lasting antihypertensive effects.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.