Sustained LDL-c lowering with PCSK9 siRNA in patients with prior MI
The effect of inclisiran in patients with prior myocardial infarction: a post hoc pooled analysis from the orion-10 and orion-11 randomized controlled trials
News - Apr. 19, 2022Presented at ACC.22 by Prof. Ulf Landmesser, MD (Berlin, Germany)
Introduction and methods
Patients who have experienced an MI are at increased risk of an recurrent ASCVD event. Major guidelines recommend stringent LDL-c goals in these patients.
This post hoc pooled analysis from the ORION-10 and ORION-11 randomized controlled trials investigated the efficacy of inclisiran on LDL-c lowering in patients with a history of MI.
A total of 1643 patients with prior MI were randomized in a 1:1 ratio to receive either 300 mg inclisiran sodium (284 mg inclisiran), or placebo on top op statin and/or ezetimibe. Inclisiran or placebo was administered at baseline, day 90 and every 6 months thereafter.
Outcomes of this analysis included percentage and absolute change in LDL-c from baseline to day 510 and time-adjusted change after day 90 and up to day 540. The analysis was stratified by time since last MI: recent (>3 months to <1 year) or remote (≥1 year).
Main results
Efficacy outcomes
Inclisiran effectively lowered LDL-c compared to placebo in patients with prior MI. There was no interaction of treatment and MI stratum on LDL-c changes:
- Between-group difference in percentage change in LDL-c from baseline to day 510 was -52.6% (95% CI -65.1 to -40.1, P≤0.0001) in patients with recent MI and -50.4% (95% CI -53.8 to -47.0, P≤0.0001) in patients with a remote MI.
- Between-group difference in absolute change from baseline to day 510 was -54.2 mg/dL (95% CI -65.7 to -42.7, P≤0.0001) in patients with recent MI and -52.2 mg/dL (95% CI -55.2 to -49.2, P≤0.0001) in patients with a remote MI.
- Between-group difference in time-adjusted change after day 90 and up to day 540 was -50.0% (95% CI -58.7 to -41.4, P≤0.0001) in patients with recent MI and -52% (95% CI -54.7 to -49.8, P≤0.0001) in patients with a remote MI.
- Between-group difference in absolute change after day 90 and up to day 540 was -50.5 mg/dL (95% CI -59.3 to -41.7, P≤0.0001) in patients with recent MI and -51.7 mg/dL (95% CI -54.0 to -49.3, P≤0.0001) in patients with a remote MI.
Safety outcomes
- A higher proportion of mild-moderate clinically relevant treatment-emergent adverse events (TEAEs) at the injection site was observed in the inclisiran arm compared to the placebo arm. Other TEAEs were similar between treatment arms and between MI strata.
Conclusion
Treatment with inclisiran, compared with placebo, in addition to statin and/or ezetimibe led to an effective and sustained LDL-c lowering in patients with prior MI.
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