zilebesiran + indapamide

**zilebesiran + indapamide** is a combination of two antihypertensive agents investigated for the treatment of uncontrolled hypertension. Zilebesiran is a chemically modified small interfering RNA (siRNA) therapeutic that selectively inhibits the hepatic synthesis of angiotensinogen, a key precursor of the renin-angiotensin-aldosterone system (RAAS), thus reducing blood pressure. Indapamide is a thiazide-like sulfonamide diuretic that acts at the proximal segment of the distal convoluted tubule in the nephron to inhibit the Na+/Cl– cotransporter, promoting renal sodium and fluid excretion, and thereby lowering blood pressure. This combination has shown significant and sustained reductions in 24-hour and office systolic blood pressure when zilebesiran is added to indapamide therapy, according to phase 2 clinical trial data (KARDIA-2 trial). Primary indication: Hypertension (uncontrolled or inadequately controlled). Developers: zilebesiran was developed by Alnylam Pharmaceuticals; indapamide is a long-established generic drug.