The impact of inclisiran on lipid profiles in adults with hyperlipidemia: a meta-analysis and meta-regression of randomized controlled trials
Abstract
Hyperlipidemia is one of the most prominent risk factors for heart diseases, and current treatments are sometimes insufficient to control it. Inclisiran, a small interfering RNA targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), provides a novel, long-acting approach to improve hyperlipidemia. This meta-analysis was conducted following the PRISMA guidelines. A total of 5 out of 185 studies screened met the inclusion criteria. The primary outcome was a reduction in the LDL-C level compared to control group. Statistical analysis used a random-effect model to calculate the mean difference (MD) for with 95% confidence interval (CI). A total of 5 randomized controlled trials comprised 4,072 patients, divided into the Inclisiran arm (n = 2,129) and the Control arm (n = 1,943). Compared with control, this study showed Inclisiran substantially reduces LDL-C (MD, -51.25%; 95% CI, [-56.58 to -45.92], p <0.00001), total cholesterol (MD, -27.75%; 95% CI, [-30.39 to -25.10], p <0.00001), apolipoprotein B (MD, -36.65%; 95% CI, [-45.93 to -27.37], p = 0.00039), triglycerides (MD, -12.39%; 95% CI, [-21.49 to -3.28], p = 0.02275), PCSK9 level (MD, -77.00%; 95% CI, [-86.89 to -67.11], p = 0.00014), and lipoprotein (a) (MD, -21.77%; 95% CI, [-24.29 to -19.24], p = 0.000018). Inclisiran also significantly increases HDL-C levels by a mean difference of +5.86% (MD, 95% CI, [+4.77 to +6.95], p = 0.0001). This meta-analysis demonstrates that Inclisiran significantly improves lipid prof…
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PCSK9-directed siRNA therapy (inclisiran) predominantly lowers LDL-C with modest triglyceride effects.
“Finally, PCSK9-directed siRNA therapy (inclisiran), which predominantly lowers LDL-C with modest triglyceride effects, further illustrates how distinct RNAi targets yield divergent lipid profiles (Khalil et al., 2025).”
From Efficacy and safety of small interfering RNA (siRNA) therapies for hypertriglyceridemia and mixed dyslipidemia: an updated systematic review and meta-analysis (2026) · cites this paper as Khalil et al., 2025
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- Authors
- Khalil, I., Rahman, M. T., & Hossain, I.
- Affiliations
- Dhaka Medical College and Hospital (BD)
- University of Dhaka (BD)
- Corresponding author
- Khalil, Ibrahim
- Venue
- The American Journal of Cardiology
- Publisher
- Elsevier BV
- Published
- 2025-09
- Volume
- 250
- Pages
- 20-29
- ISSN
- 0002-9149 (ISSN-L)
- OpenAlex
- W4409661757
- Cited by
- 8
- References
- 30
- Citations by year
- 2026: 7 · 2025: 1
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- The American Journal of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- inclisiran, hyperlipidemia, PCSK9 inhibition, siRNA, LDL cholesterol, lipid profile, apolipoprotein B, triglycerides, lipoprotein(a), HDL cholesterol, PCSK9, cardiovascular risk reduction, statin-resistant hypercholesterolemia, familial hypercholesterolemia, LDL apheresis
- MeSH terms
- Proprotein Convertase 9, Humans, Hyperlipidemias, Lipids, Cholesterol, LDL, Triglycerides, Randomized Controlled Trials as Topic
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