Inclisiran add-on to max statins yields steep LDL reductions

  • Ray KK & al.
  • N Engl J Med
  • 18.03.2020

  • von Emily Willingham, PhD
  • Clinical Essentials
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Takeaway

  • Inclisiran in patients at high risk for cardiovascular disease on their maximum-tolerated statin dose yielded additional ~50% decreases in low-density lipoprotein cholesterol (LDL).
  • This pair of phase 3 trials (ORION-10 and ORION-11) suggest benefit of inclisiran injection every 6 months.

Why this matters

  • These results confirm preliminary findings and open the way to another therapeutic option in this high-risk patient group.

Key results

  • ORION-10 included 1561 patients, and ORION-11 included 1617.
  • Most patients were on high-intensity statins:
    • ORION-10: 68.0%. 
    • ORION-11: 78.6%.
  • Mean baseline LDL:
    • ORION-10: 104.7±38.3 mg/dL.
    • ORION-11: 105.5±39.1 mg/dL.
  • At 510 days, LDL reductions from baseline with inclisiran vs placebo:
    • ORION-10: 52.3% (95% CI, 48.8%-55.7%).
    • ORION-11: 49.9% (95% CI, 46.6%-53.1%).
    • Both P<.001 vs placebo.>
  • Serious adverse events vs placebo:
    • ORION-10: 22.4% vs 26.3%.
    • ORION-11: 22.3% vs 22.5%.
  • These rates included deaths, as follows:
    • ORION-10: 1.5% vs 1.4%.
    • ORION-11: 1.7% vs 1.9%.

Study design

  • 2 randomized controlled trials.
  • Inclisiran 284 mg administered via subcutaneous injection, day 1, day 90, and every 6 months thereafter to 540 days.
  • Funding: Medicines Company.

Limitations

  • Small number of nonadjudicated cardiovascular events.
  • Defined clinical population; generalizability not clear.