Prediction of inclisiran efficacy in patients with established atherosclerotic cardiovascular disease: the SIRIUS in-silico modelling of cardiovascular outcomes - Summary - MDSpire

Prediction of inclisiran efficacy in patients with established atherosclerotic cardiovascular disease: the SIRIUS in-silico modelling of cardiovascular outcomes

  • By

  • Denis Angoulvant

  • Emmanuel Peyronnet

  • Bertrand Cariou

  • Pierre Amarenco

  • Franck Boccara

  • Jean-Pierre Boissel

  • Alexandre Bastien

  • Eulalie Courcelles

  • Alizée Diatchenko

  • Anne Filipovics

  • Solène Granjeon-Noriot

  • Riad Kahoul

  • Guillaume Mahé

  • Lolita Portal

  • Solène Porte

  • Yishu Wang

  • Emmanuelle Bechet

  • Philippe Gabriel Steg

  • December 26, 2025

  • 0 min

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Objective:

To predict the efficacy of inclisiran on major adverse cardiovascular events (MACE) in virtual patients with atherosclerotic cardiovascular disease (ASCVD) using the SIRIUS in-silico modelling programme.

Key Findings:
  • Inclisiran predicted to reduce LDL-C by 49.7% compared to placebo.
  • 25.2% reduction in 5-year risk of 3-point MACE (11.3% vs. 14.9%).
  • 34.8% reduction in myocardial infarction risk (5.7% vs. 8.6%; HR 0.65).
  • 26% reduction in ischaemic stroke risk (2.6% vs. 3.4%; HR 0.74).
  • 34.1% reduction in major adverse limb events (0.5% vs. 0.8%; HR 0.66).
  • 7.1% relative reduction in cardiovascular death (4.2% vs. 4.5%; HR 0.93).
Interpretation:

The SIRIUS model provides early insights into inclisiran's potential cardiovascular benefits, suggesting significant reductions in LDL-C and MACE risk in ASCVD patients.

Limitations:
  • Model did not account for non-adherence, recurrent events, or adverse effects.
Conclusion:

The SIRIUS in-silico simulation offers a predictive framework for understanding inclisiran's impact on cardiovascular outcomes, pending results from ongoing Phase 3 trials.

Original Source(s)

Prediction of inclisiran efficacy in patients with established atherosclerotic cardiovascular disease: the SIRIUS in-silico modelling of cardiovascular outcomes

  • by Denis Angoulvant, Emmanuel Peyronnet, Bertrand Cariou, Pierre Amarenco, Franck Boccara, Jean-Pierre Boissel, Alexandre Bastien, Eulalie Courcelles, Alizée Diatchenko, Anne Filipovics, Solène Granjeon-Noriot, Riad Kahoul, Guillaume Mahé, Lolita Portal, Solène Porte, Yishu Wang, Emmanuelle Bechet, Philippe Gabriel Steg

  • December 26, 2025

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