Affiliation:
1. Sharif University of Technology
2. Shahid Beheshti University of Medical Sciences
3. Shahid Bahonar University of Kerman
4. Zabol University of Medical Sciences
5. University of Kashan
6. Ilam University
7. Kermanshah University of Medical Sciences
8. Gerash University of Medical Sciences
Abstract
Abstract
Background:
Familial Hypercholesterolemia (FH) is a genetic disorder in lipoprotein metabolism caused by mutations that increase LDL and total cholesterol levels. High LDL and cholesterol levels increase atherosclerosis risk. FH mutations impact the LDL receptor (LDLR) gene, apolipoprotein B, and PCSK9. About 20% of FH cases have a polygenic basis that affects LDL levels. We decided to conduct a systematic review of the available research in this field to provide a thorough genes/proteins network meta-analysis on the impact of drug combinations on the management of heterozygous Familial Hypercholesterolemia (HeFH). This paper reviews and analyzes the literature on the effects of medication combinations on HeFH management. This study investigates articles that analyzed the management and adjuvants of HeFH to recommend forceful drug combinations.
Methods:
This systematic review and network meta-analysis analyzed the Science Direct, Embase, Scopus, PubMed, Web of Science (ISI), and Google Scholar databases without a lower time limit and up to July 2022. The current study consists of three fundamental stages. Firstly, drug combinations are recommended by reinforcement learning. In the second stage, we used a systematic review to analyze RL's outcomes in diverse populations (with a variety of ages, sex, etc.). Natural Language Processing (NLP) employs context to search these articles. We contrasted manual and NLP-based searches and discovered that NLP could find articles based on MeSH, not simply words. In stage three, we analyze RL outcomes using network meta-analysis.
Results:
This study uses the RAIN method to investigate the most effective medication combination for managing Heterozygous Familial Hypercholesterolemia (HeFH). Results from the method indicate that the best-recommended scenario is 2.7 times more efficient than the prescription of Ezetimibe as the initial scenario.
Conclusion:
Our systematic review and network meta-analysis review indicate that a drug combination of Ezetimibe, Pravastatin, and Simvastatin is highly effective. However, additional high-quality clinical trials are required to determine the efficacy and safety of other treatments.
Publisher
Research Square Platform LLC
Reference56 articles.
1. Cuchel M, Bruckert E, Ginsberg HN, Raal FJ, Santos RD, Hegele RA et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014 Aug 21;35(32):2146–57.
2. Khera AV, Won HH, Peloso GM, Lawson KS, Bartz TM, Deng X et al. Diagnostic Yield and Clinical Utility of Sequencing Familial Hypercholesterolemia Genes in Patients With Severe Hypercholesterolemia.J Am Coll Cardiol. 2016 Jun7;67(22):2578–89.
3. The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients;Jansen ACM;J Intern Med
4. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment;Rader DJ;J Clin Invest
5. Graham CA, Latten MJ, Hart PJ. Molecular diagnosis of familial hypercholesterolaemia.Curr Opin Lipidol. 2017Aug;28(4):313–20.