This article provides a comprehensive review of recent developments and clinical trials in pharmacological approaches for uncontrolled hypertension. It covers a wide range of novel agents and treatment strategies, including:
Single-Pill Combinations (SPCs): SPCs offer a convenient and cost-effective approach to managing hypertension. Studies have shown that SPCs, such as amlodipine, hydrochlorothiazide, and valsartan, are more effective than doubling the dose of a single drug and lead to reduced cardiovascular events.
Quadpills: Quadpills, containing low-dose combinations of four antihypertensive drugs, have demonstrated significant BP reduction compared to single-agent therapy.
Synthetic Small Interfering RNAs (siRNAs): siRNAs, such as zilebesiran, target the synthesis of angiotensinogen, a key protein involved in RAAS activation. Clinical trials have shown promising results with zilebesiran, leading to significant BP reductions.
Antisense Oligonucleotides: IONIS-AGT-LRx, a subcutaneous antisense oligonucleotide targeting AGT mRNA, has shown potential in reducing plasma angiotensinogen levels, but further research is needed to confirm its efficacy in lowering BP.
Aldosterone Synthase Inhibitors (ASIs): ASIs, such as baxdrostat and lorundrostat, provide a mechanism to consistently reduce aldosterone synthesis. Phase III trials are ongoing to evaluate their efficacy and safety.
Mineralocorticoid Receptor Antagonists (MRAs): MRAs, such as spironolactone, eplerenone, esaxerenone, and finerenone, reduce fluid overload and lower BP by preventing sodium reabsorption. Newer non-steroidal MRAs offer improved selectivity and adverse effect profiles.
Angiotensin Receptor-Neprilysin Inhibitors (ARNIs): ARNIs, such as sacubitril-valsartan, combine an angiotensin receptor blocker with a neprilysin inhibitor, leading to effective antihypertensive and antifibrotic effects.
Natriuretic Peptide Pathway Agonists: REGN5381, an agonist antibody that directly activates natriuretic peptide receptor 1, has shown potential in lowering BP in a first-in-human study.
Endothelin Receptor Antagonists (ERAs): ERAs, such as bosentan, darusentan, and aprocitentan, block the effects of endothelin-1, a potent vasoconstrictor. Aprocitentan has recently been approved by the FDA for the treatment of uncontrolled hypertension.
Phosphodiesterase Type 5 (PDE5) Inhibitors: PDE5 inhibitors, such as sildenafil, increase cGMP availability, leading to vasodilation and BP reduction. Further research is needed to explore their potential as antihypertensive drugs.
This article highlights the ongoing research and development of novel pharmacological approaches for uncontrolled hypertension. These advancements offer promising new treatment options for patients with this prevalent condition.