Inclisiran: a systematic review exploring the revolutionary approach of twice-yearly dosing regimen in the treatment of hypercholesterolemia
Open accessAbstract
The global burden of hyperlipidemia is on the rise, along with an increase in associated cardiovascular complications. Since most of the patients affected by hyperlipidemia are elderly individuals with multiple comorbidities, the introduction of even a single additional drug for asymptomatic conditions such as hyperlipidemia can drastically reduce treatment compliance due to their long medication history. Hence, researchers are trying to come up with a drug with a long duration of action requiring less frequent dosing without compromising compliance and improving the outcome. This led to the discovery of inclisiran, a "wonder drug" that utilizes small interference RNA and requires only twice-yearly administration to maintain patients' lipid levels at optimal levels. We conducted a systematic review by following standardized guidelines on the long-term efficacy and safety of the new drug, inclisiran, in the treatment of hypercholesterolemia. We conducted an advanced search on PubMed using the MeSH strategy and then employed appropriate keywords to search other major databases, such as PubMed Central and Medline, using various inclusion and exclusion criteria, which yielded 94 articles from various databases. We narrowed down the search to 10 randomized controlled trials (ORION trials) after removing duplicates and screening for irrelevant titles for inclusion in the study. The ORION trials on inclisiran evaluated the drug's impact on various parameters, such as low-density lipoprotein-cholesterol (LDL-C), proprotein convertase subtilisin/kexin type 9 (PCSK9), high-density lipoprotein (non-HDL), apolipoprotein B (apoB), and so on, while considering the safety aspects of the drug. All the trials indicate greater efficacy of inclisiran and long-term maintenance of the results achieved when compared to a placebo and showed a long dosing interval, thereby increasing treatment compliance. Additionally, as the drug's dose increased, we observed greater reductions in the mentioned parameters without a significant increase in the incidence of adverse events. According to the review's data analysis, inclisiran, with its greater efficacy, has the potential to replace conventional pharmacological therapy in the near future, with the best results achieved when combined with lifestyle modifications. However, a long-term assessment of the drug's efficacy and safety is required before implementing it in clinical practice to identify any potential safety concerns, particularly related to the administration of higher dosage over a longer period.
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Inclisiran's twice-yearly dosing schedule may improve adherence, particularly in high-risk populations where sustained LDL-C reduction is critical.
“Its twice-yearly dosing schedule may improve adherence, particularly in high-risk populations where sustained LDL-C reduction is critical.17”
From Small Interfering RNA for LDL-Cholesterol Reduction (2026) · cites this paper as [17]
The Review (page not provided) says twice-yearly dosing may improve adherence while maintaining substantial LDL-C reductions. It also reports sustained LDL-C reductions in patients with high cardiovascular risk factors, but does not establish that the adherence benefit is particularly pronounced in high-risk populations. (LLM, conf=0.84)
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Small Interfering RNA for LDL-Cholesterol Reduction
Batista, F., Mamede, I., & Dacoregio, M. (2026) · JACC: Advances · doi:10.1016/j.jacadv.2026.102932
- Authors
- Singareddy, S., Dhakal, S., Limbaña, T. A., Murugan, V., Nazmin, F., Garcia, J., & Khan, S.
- Affiliations
- California Institute of Behavioral Neurosciences and Psychology (United States) (US)
- Corresponding author
- Singareddy, Sanjana
- Venue
- Cureus
- Published
- 2024-09-22
- Volume
- 16
- Issue
- 9
- Pages
- e69918-e69918
- ISSN
- 2168-8184 (ISSN-L)
- PMC
- PMC11495418
- OpenAlex
- W4402714716
- Cited by
- 0
- References
- 26
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- diamond
- dx.doi.org
- Licence
- cc-by
- Locations
- Cureus (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- 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, hypercholesterolemia, hyperlipidemia, siRNA, PCSK9 inhibition, LDL cholesterol, apolipoprotein B, non-HDL cholesterol, medication adherence, drug safety, lifestyle modification
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