First clinical experiences with inclisiran in a real-world setting

Janneke W C M Mulder; Annette M H Galema-Boers; Jeanine E Roeters van Lennep

doi:10.1016/j.jacl.2023.09.005

First clinical experiences with inclisiran in a real-world setting

J Clin Lipidol. 2023 Nov-Dec;17(6):818-827. doi: 10.1016/j.jacl.2023.09.005. Epub 2023 Sep 18.

Authors

Janneke W C M Mulder¹, Annette M H Galema-Boers¹, Jeanine E Roeters van Lennep²

Affiliations

¹ Department of Internal Medicine, Erasmus University Medical Center, PO Box 2040, Rotterdam, CA 3000, the Netherlands.
² Department of Internal Medicine, Erasmus University Medical Center, PO Box 2040, Rotterdam, CA 3000, the Netherlands. Electronic address: j.roetersvanlennep@erasmusmc.nl.

PMID: 37775462
DOI: 10.1016/j.jacl.2023.09.005

Abstract

Background and objective: Inclisiran is the first-in-class small interfering RNA (siRNA) proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor. In clinical trials inclisiran showed effective and sustained low-density lipoprotein cholesterol (LDL-C) reduction of ± 50 %. As data in clinical setting are scarce, we aim to investigate the efficacy and safety in clinical practice.

Methods: We describe a registry of consecutive patients who started with inclisiran at a lipid clinic of a university hospital. Patients were eligible if they fulfilled the reimbursement criteria in the Netherlands. Patients were included if they started with inclisiran as first line (group 1) or switched from PCSK9 monoclonal antibody (mAbs) to inclisiran (group 2). LDL-C levels were measured at 3 and 9 months after initiation of inclisiran. Median change of LDL-C levels was calculated on an individual and group level.

Results: We analysed 65 patients (36 women), median [25^th percentile; 75^th percentile] age of 63 [54; 68] years. Of these, 44 patients had both a 3 month and 9 month visit. At 3 months, patients who newly started inclisiran (group 1, n = 45) showed a LDL-C decrease of 38 [-49;-33] %. Patients who used statins as co-medication (n = 15) had a higher median LDL-C decrease compared to those without statin use (n=30; 45 % vs 38 %). However, patients who switched from mAbs to inclisiran (group 2, n = 20) had an increase in LDL-C of 38 [+4; +97] %. Adverse effects associated with inclisiran were mild and consisted of mild injection site reactions. Efficacy was slightly less whereas safety results were similar at 9 months.

Conclusion: Our initial experience of inclisiran in a clinical setting showed less reduction in LDL-C levels compared to clinical trials but a similar safety profile. Moreover, patients who switched from PCSK9 mAbs to inclisiran generally showed an increase in LDL-C levels implying that inclisiran is less potent in LDL-C reduction compared to PCSK9 mAbs.

Keywords: Cardiovascular disease; Efficacy; Lipid lowering therapy; PCSK9 inhibition; Safety.

MeSH terms

Anticholesteremic Agents* / therapeutic use
Cholesterol, LDL
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
Proprotein Convertase 9
RNA, Small Interfering / adverse effects

Substances

Cholesterol, LDL
PCSK9 protein, human
Proprotein Convertase 9
ALN-PCS
RNA, Small Interfering
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents