Publication bias in pharmacogenetics of statin-associated muscle symptoms: A meta-epidemiological study.

IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
A Gougeon, I Aribi, S Guernouche, J C Lega, J M Wright, C Verstuyft, A Lajoinie, F Gueyffier, G Grenet
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引用次数: 0

Abstract

Background and aims: Statin-associated muscle symptoms (SAMS) are a major cause of treatment discontinuation. Clinical Pharmacogenetics Implementation Consortium (CPIC) recommend dose adjustment for statin treatment according to known SLCO1B1 genotype to reduce SAMS. We hypothesized that the association between SLCO1B1 genotype and SAMS is misestimated because of publication bias.

Methods: We searched published systematic reviews on the association between SLCO1B1 genotype and SAMS. To assessed publication bias, we used funnel plot visual inspection, Egger's test, and the Bayes Factor (BFPublication-bias) from Robust Bayesian Meta-Analysis (RoBMA). We compared the odds ratios (ORUncorrected) from meta-analyses before and after correcting for publication bias using trim-and-fill (ORTrim&Fill) and RoBMA (ORRoBMA) methods.

Results: We included 8 cohort and 11 case-control studies, totaling 62 OR of three SLCO1B1 genotypes and six statin drugs. In the primary analysis, the funnel plot was suggestive of publication bias, confirmed by Egger's test (p=0.001) and RoBMA (BFPublication-bias = 18). Correcting the estimate for publication bias resulted in loss of the association, from a significant ORUncorrected (1.31 95%CI [1.13-1.53]) to corrected ORs suggesting no difference: ORTrim&Fill (1.07 95%CI [0.89-1.30]) and ORRoBMA (1.02 95%CI [1.00-1.33]). This suggested that publication bias overestimated the association by 18 % and 23 %, respectively. Similar results were found for genotype rs4149056, simvastatin and atorvastatin.

Conclusions: The effect of the SLCO1B1 genotype on the risk of developing SAMS is overestimated in the published literature, especially rs4149056. This could lead prescribers to incorrectly decreasing statin doses or even avoiding statin use, leading to a loss of the potential cardiovascular benefit of statins.

他汀类药物相关肌肉症状药物遗传学的发表偏差:一项荟萃流行病学研究。
背景和目的:他汀类药物相关肌肉症状(SAMS)是导致治疗中断的主要原因。临床药物遗传学实施联合会(CPIC)建议根据已知的 SLCO1B1 基因型调整他汀类药物治疗剂量,以减少 SAMS。我们假设,由于发表偏倚,SLCO1B1 基因型与 SAMS 之间的关联被错误估计:我们检索了已发表的有关 SLCO1B1 基因型与 SAMS 之间关系的系统综述。为了评估发表偏倚,我们使用了漏斗图目测、Egger 检验和稳健贝叶斯荟萃分析(Robust Bayesian Meta-Analysis,RoBMA)中的贝叶斯因子(BFPublication-bias)。我们比较了使用修剪与填充(ORTrim&Fill)和RoBMA(ORRoBMA)方法纠正发表偏倚前后荟萃分析的几率比(ORUncorrected):我们纳入了 8 项队列研究和 11 项病例对照研究,共计 62 个 OR,涉及 3 种 SLCO1B1 基因型和 6 种他汀类药物。在主要分析中,漏斗图提示存在发表偏倚,Egger 检验(P=0.001)和 RoBMA(BFP 发表偏倚 = 18)证实了这一点。对发表偏倚的估计值进行校正后,相关性消失,从显著的未校正 OR(1.31 95%CI [1.13-1.53])变为校正 OR,表明没有差异:ORTrim&Fill(1.07 95%CI [0.89-1.30])和 ORRoBMA(1.02 95%CI [1.00-1.33])。这表明,发表偏倚分别高估了 18% 和 23% 的相关性。基因型 rs4149056、辛伐他汀和阿托伐他汀也发现了类似的结果:结论:在已发表的文献中,SLCO1B1 基因型对罹患 SAMS 风险的影响被高估了,尤其是 rs4149056。这可能会导致处方者错误地减少他汀类药物的剂量,甚至避免使用他汀类药物,从而失去他汀类药物对心血管的潜在益处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Atherosclerosis
Atherosclerosis 医学-外周血管病
CiteScore
9.80
自引率
3.80%
发文量
1269
审稿时长
36 days
期刊介绍: Atherosclerosis has an open access mirror journal Atherosclerosis: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Atherosclerosis brings together, from all sources, papers concerned with investigation on atherosclerosis, its risk factors and clinical manifestations. Atherosclerosis covers basic and translational, clinical and population research approaches to arterial and vascular biology and disease, as well as their risk factors including: disturbances of lipid and lipoprotein metabolism, diabetes and hypertension, thrombosis, and inflammation. The Editors are interested in original or review papers dealing with the pathogenesis, environmental, genetic and epigenetic basis, diagnosis or treatment of atherosclerosis and related diseases as well as their risk factors.
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