A promising new injectable treatment offers hope for millions struggling with high blood pressure that resists standard daily medications.
High blood pressure drives heart attacks, strokes, and other serious issues, yet many patients can’t achieve good control even on multiple pills—often due to adherence challenges.
The KARDIA-2 Phase 2 trial, published in JAMA, tested zilebesiran (from Alnylam and Roche) in 663 adults with persistently elevated readings despite ongoing therapy. Participants kept their usual meds, but some received a single subcutaneous injection of zilebesiran every six months.
Those getting the shot experienced significantly greater and more sustained blood pressure reductions compared to placebo—clinically meaningful drops that lasted up to six months.
Zilebesiran uses RNA interference to target the liver’s production of angiotensinogen, a key driver of vessel constriction in the renin-angiotensin system. Lowering it relaxes blood vessels for longer-lasting control, potentially slashing the need for daily pills.
As Dr. Manish Saxena, a lead investigator, noted: “This could transform management for patients with poor control—one injection every six months improves adherence and consistency.”
The drug showed a favorable safety profile in this add-on setting.
Since the trial, the program has progressed: KARDIA-3 provided further insights in higher-risk patients, paving the way for the ongoing ZENITH Phase 3 cardiovascular outcomes trial (started late 2025), which will test if zilebesiran reduces major events like heart attacks and strokes in ~11,000 high-risk patients.
If successful, this biannual approach could mark a major shift in hypertension care—delivering steadier control, better adherence, and fewer complications for those not helped enough by traditional treatments. Exciting times ahead in cardiovascular innovation!