Phase Ii Trial Finds Zilebesiran Lowers Systolic Blood Pressure In Patients With Uncontrolled Hypertension

The double-blind, placebo-controlled, randomized proceedings was conducted successful 5 countries. The proceedings included big patients pinch established CVD aliases precocious cardiovascular consequence (10-year atherosclerotic CVD consequence people >15% aliases an estimated glomerular filtration complaint [eGFR] 30-59 mL/min/1.73 m2) pinch uncontrolled hypertension (mean screening agency systolic BP [SBP] 140-170 mmHg and 24-hour mean ambulatory SBP 130-170 mmHg) connected 2 to 4 antihypertensives (including either a calcium transmission blocker aliases a diuretic). Results were analysed from participants pinch eGFR ≥45 mL/min/1.73 m2; results from participants pinch eGFR 30 to <45 mL/min/1.73 m2 will beryllium reported separately. Participants successful this study were randomized 1:1:1 to a azygous subcutaneous dose of zilebesiran 300 mg aliases 600 mg aliases placebo. In nan first 3 months, investigators were encouraged not to alteration nan inheritance antihypertensive therapy unless SBP was >160 mmHg aliases unless clinically indicated. After 3 months, investigators could intensify antihypertensive therapy for patients pinch persistent SBP >140 mmHg. The superior result was alteration from baseline successful mean agency SBP astatine 3 months.

The 270 patients analysed had a median property of 67 years and 45% were female. Approximately 23% had anterior CVD and 77% were astatine precocious cardiovascular risk. At baseline, mean agency SBP and diastolic BP (DBP) were 144 mmHg and 80 mmHg, respectively, while mean 24-hour ambulatory SBP and DBP were 142 mmHg and 79 mmHg, respectively. Participants were connected 2 (53%), 3 (36%) aliases 4 (11%) antihypertensives astatine baseline.

For nan superior endpoint, nan placebo-adjusted mean alteration successful agency SBP astatine Month 3 was − 5.0 mmHg (95% assurance interval [CI] −9.9 to −0.2) pinch zilebesiran 300 mg and −3.3 mmHg (95% CI −8.2 to 1.6) pinch zilebesiran 600 mg. Neither were statistically important aft adjusting for multiplicity.

Placebo-adjusted mean changes successful agency SBP astatine Month 6 were −3.9 (95% CI −8.5 to 0.7) and −3.6 (95% CI −8.2 to 1.0) for zilebesiran 300 mg and 600 mg, respectively. Placebo-adjusted mean changes successful 24-hour ambulatory SBP astatine Month 6 were −5.5 mmHg (95% CI −9.4 to −1.5) and −7.4 mmHg (95% CI −11.3 to −3.4) for zilebesiran 300 mg and 600 mg, respectively. Placebo-adjusted alteration successful nighttime SBP astatine Month 6 was −6.6 mmHg (95% CI −11.0 to −2.2) pinch 300 mg and −8.2 mmHg (95% CI −12.6 to −3.8) pinch 600 mg. Because nan superior endpoint was not statistically significant, value for secondary outcomes could not beryllium claimed.

In a post-hoc study of patients receiving a diuretic pinch SBP ≥140 mmHg astatine baseline, zilebesiran 300 mg resulted successful placebo-adjusted mean agency SBP lowering of −9.2 mmHg (95% CI −17.3 to −1.2) astatine Month 3.

For nan double-blind period, astir adverse events, including hyperkalaemia, kidney dysfunction and hypotension, were mild aliases moderate, non-serious and transient, pinch fewer requiring intervention. Across study arms, superior adverse events were observed successful 3.8% and 4.5% successful zilebesiran and placebo-treated patients, respectively.

Summarizing, Doctor Pagidipati said: "In KARDIA-3, a azygous dose of zilebesiran 300 mg led to a 5-mmHg simplification successful SBP astatine 3 months compared pinch placebo, a quality which did not scope statistical significance. However, nan proceedings met its nonsubjective of informing nan creation of early trials. The totality of nan grounds from nan shape II programme supports nan behaviour of a shape III outcomes proceedings to further measure nan imaginable of zilebesiran for improving cardiovascular outcomes successful patients pinch uncontrolled hypertension."