Efficacy of Inclisiran in patients having familial hypercholesterolemia: heterozygous compared to homozygous trait, a systematic review and meta analysis

Rahul Rai; Payal Devi; Kapeel Kumar; Kainat Naeem; Hanesh Kumar; Kajal Kumari; Anish Kumar; Aman Kumar; Aqeel Muhammad; Muhammad Sohaib Khan; Ghulam Qadir; Shaheryar Ali; Mahveer Maheshwari; Muhammad Jawwad

doi:10.1097/HPC.0000000000000353

Efficacy of Inclisiran in patients having familial hypercholesterolemia: heterozygous compared to homozygous trait, a systematic review and meta analysis

Crit Pathw Cardiol. 2024 Mar 6. doi: 10.1097/HPC.0000000000000353. Online ahead of print.

Authors

Affiliations

¹ Department of Medicine and Surgery, Liaquat University of medical and health sciences, Jamshoro, Pakistan.
² Department of Medicine and Surgery, People university of medical and health sciences, Nawabshah, Pakistan.
³ Department of Medicine and Surgery, Avicenna medical college, Lahore, Pakistan.
⁴ Department of Medicine and Surgery, Hubei university of arts and science medical college, Hubei, China.
⁵ Department of Medicine and Surgery, Dow University of Health Sciences, Karachi, Pakistan.
⁶ Department of Medicine and Surgery, Chandka Medical College(SMBBMU) Larkana, Pakistan.

PMID: 38446086
DOI: 10.1097/HPC.0000000000000353

Abstract

Objective: To find out whether Inclisiran sodium has different efficacy in heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH) patient groups.

Methods: We conducted the systematic review and meta analysis of ORION Clinical Trials Pubmed, Embase and Clinicaltrials.gov databases were searched for the relevant studies.Atheroscalerotic parameters considered for our objective were LDL-C,Total cholesterol,PCSK9, Apolipoportien-B, and Non HDL-C. Primary outcomes were the percentage difference in atheroscalerotic parameters at followup relative to baseline values. Our study examined these primary outcomes in order to determine whether there is a statistically significant difference between the HeFH and HoFH groups. Risk of bias was assessed by Cochrane risk of bias tool. Meta-analysis was performed when at least two studies reported on the same variable.

Results: Four ORION Clinical Trials provided the data related to the mean difference in the atheroscalerotic parameters at followup relative to baseline, of HeFH and HoFH patient populations, after administration of 300mg inclisiran subcutaneously. We pooled together these mean difference for each group and applied a statistical test to analyse if the values were significantly different between the groups. The results of our study unveiled the significant difference in pooled mean differences in LDL-C (HeFH:-48.62% HoFH:-9.12% p<0.05) Total cholesterol (HeFH:-30.31% HoFH:-11.50% p<0.05),Apolipoprotein(HeFH:-39.97% HoFH:-14.68% p<0.05), non HDL(HeFH:-44.51% HoFH:-12.22% p<0.05) between HeFH and HoFH groups. However the difference in pooled mean difference in PCSK9 values (HeFH:-68.41% HoFH:-56.25% p=0.2)between HeFH and HoFH groups, was statistically insignificant. Studies were of high quality.

Conclusion: There was significant difference in the reductions in atherosclerotic lipid parameters in heterozygous and homozygous populations after the administration of Inclisiran except for PCSK9 parameter. Further studies are needed to support this conclusion.