Inclisiran in patients with prior myocardial infarction: A post hoc pooled analysis of the ORION-10 and ORION-11 Phase 3 randomised trials

Atherosclerosis. 2023 Dec:386:117354. doi: 10.1016/j.atherosclerosis.2023.117354. Epub 2023 Oct 18.


Background and aims: Among patients with prior myocardial infarction (MI), the risk of future ischaemic cardiovascular events is increased, and intensive lipid-lowering therapy (LLT) is indicated to achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals. Here, the efficacy and safety of inclisiran, a small interfering ribonucleic acid, were evaluated in patients with or without prior MI from the pooled ORION-10 and ORION-11 Phase 3 trials.

Methods: Patients (n = 2636) were randomised 1:1 to receive 284 mg inclisiran (300 mg inclisiran sodium) or placebo on Day 1, Day 90, and 6-monthly thereafter over 18 months, along with background oral LLT, including statins. Of these, 1643 (62.3%) patients had an MI prior to randomisation, stratified as recent (>3 months to <1 year) or remote (≥1 year), and 993 (37.7%) patients were without a prior MI. The percentage change in LDL-C from baseline and safety were assessed.

Results: Baseline characteristics were well balanced across the treatment arms and MI strata. The mean (95% confidence interval) placebo-corrected LDL-C reductions from baseline to Day 510 with inclisiran were 52.6% (40.1, 65.1), 50.4% (47.0, 53.8), and 51.6% (47.4, 55.9) for recent, remote, and no prior MI, respectively. Corresponding time-adjusted LDL-C reductions were 50.0% (41.4, 58.7), 52.2% (49.8, 54.7), and 51.2% (48.1, 54.2). In each MI stratum, treatment-emergent adverse events (TEAEs) at the injection site (all mild to moderate) were observed more in inclisiran-treated patients than placebo, without an excess of other TEAEs.

Conclusions: Inclisiran provided effective and consistent LDL-C lowering, irrespective of MI status.

Keywords: Inclisiran; LDL-C goals; Myocardial infarction.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents* / therapeutic use
  • Cholesterol, LDL
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects
  • Myocardial Infarction* / chemically induced
  • Myocardial Infarction* / drug therapy
  • Proprotein Convertase 9
  • RNA, Small Interfering / adverse effects


  • Cholesterol, LDL
  • RNA, Small Interfering
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Anticholesteremic Agents
  • Proprotein Convertase 9