- Question
- Can inclisiran, a small interfering RNA that inhibits hepatic PCSK9 synthesis, produce sustained LDL cholesterol reductions with infrequent dosing in patients with atherosclerotic cardiovascular disease?
- Design
- Phase 3, randomized 1:1, double-blind, placebo-controlled trial enrolling 1561 patients in ORION-10; the publication reports this trial together with ORION-11. Follow-up covered 540 days.
- Population
- Patients with atherosclerotic cardiovascular disease and elevated LDL cholesterol despite maximum tolerated statin therapy. Mean baseline LDL cholesterol was 104.7 mg/dl (2.71 mmol/l).
- Intervention
- Inclisiran 284 mg by subcutaneous injection on day 1, day 90, and every 6 months thereafter.
- Control
- Placebo (saline) given by subcutaneous injection on the same schedule.
- Primary outcome
- The two coprimary end points were the placebo-corrected percentage change in LDL cholesterol from baseline to day 510 and the time-adjusted percentage change in LDL cholesterol after day 90 and up to day 540.
- Results
- In ORION-10, inclisiran reduced LDL cholesterol by 52.3% (95% CI, 48.8 to 55.7) at day 510, and the time-adjusted reduction was 53.8% (95% CI, 51.3 to 56.2), with P<0.001 versus placebo for both comparisons.
- Safety
- Adverse events were generally similar between inclisiran and placebo, although injection-site reactions were more frequent with inclisiran (2.6% vs. 0.9% in ORION-10); they were generally mild and none were severe or persistent.
- Conclusion
- Inclisiran given subcutaneously every 6 months produced LDL cholesterol reductions of approximately 50%, with more injection-site reactions than placebo.
- Why it matters
- It showed that a twice-yearly treatment can durably lower LDL cholesterol in patients not at goal on statins, expanding lipid-lowering options built on the PCSK9 pathway.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 14, 2026