Despite the availability of effective antihypertensive therapies, global blood pressure control rates remain unacceptably low. Contributing factors, such as low treatment adherence, therapeutic inertia, and rising multimorbidity, underscore the need for innovative approaches to improve hypertension care. New antihypertensive drug therapies that act on physiological pathways beyond those targeted by conventional drug classes are emerging. These therapies include small interfering RNA agents that inhibit angiotensinogen synthesis as a novel approach to inhibit the renin-angiotensin system, and new strategies to more selectively modulate aldosterone, such as aldosterone synthase inhibitors and non-steroidal mineralocorticoid receptor antagonists. There is also growing interest in therapies to enhance the action of the natriuretic peptide system. Although these innovations present valuable therapeutic opportunities, their benefits must be carefully balanced against considerations of safety, cost, clinical outcomes, and equitable access-all of which are crucial to reducing the residual burden of cardiovascular and chronic kidney disease.
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