Effects of Delivering SLCO1B1 Pharmacogenetic Information in Randomized Trial and Observational Settings
Effects of Delivering SLCO1B1 Pharmacogenetic Information in Randomized Trial and Observational Settings
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DOI：
10.1161/circgen.118.002228
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发表时间：
2018-09-01
影响因子：
7.4
通讯作者：
Voora, Deepak
中科院分区：
文献类型：
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作者：
Peyser, Bruce;Perry, Emily P.;Voora, Deepak
背景技术背景：根据溶质载体有机阴离子转运蛋白家族成员1B 1（SLCO 1B 1）药物遗传毒性信息定制他汀类药物对患者，供应商和药理学结局的结果是未知的。方法：该试验随机分配159例患者不服用他汀类药物，因为以前他汀类药物肌痛1：1接受SLCO 1B 1 GIST（基因型知情他汀类药物治疗）与常规护理（UC），并随访长达8个月。UC组在试验后收到了SLCO 1B 1结果。主要结局是使用Morisky药物依从性量表评估他汀类药物依从性，该量表在重新开始他汀类药物治疗的患者中进行评估。在所有参与者中评估的次要结局包括试验内和试验后他汀类药物重新开始和LDL c（低密度脂蛋白胆固醇）。使用商业实验室数据，系列LDLc之间进行了比较1907患者接受SLCO 1B 1测试和倾向匹配，未经测试的controls.RESULTS：试验参与者25% SLCO 1B 1 *5载体。两组间他汀类药物依从性相似（GIST与UC的Morisky药物依从性量表，6.8 +/- 1.5 vs 6.9 +/- 1.6，P=0.96）。GIST导致更多的新他汀类药物处方（55.4% vs 38.0%，P=0.04）和3个月时较低的LDL c（131.9 +/- 42.0 vs 144.4 +/- 43.0 mg/dL; P=0.048），8个月时的幅度相似（128.6 +/- 37.9 vs 141.0 +/- 44.4; P=0.12）。SLCO 1B 1 *5携带者在GIST中的LDLc下降幅度大于UC（相互作用P=0.048）。试验后，与分配至GIST的受试者相比，交叉至GIST的UC受试者的LDL c降低（-14.9 +/- 37.8 vs +9.0 +/- 37.3 mg/dL，P=0.03）。患者测试SLCO 1B 1虽然商业实验室有更大的低密度脂蛋白降低（P=0.04）相比controls.CONCLUSIONS：交付SLCO 1B 1药物遗传学测试，解决他汀类肌痛改善他汀类药物重新启动和低密度脂蛋白，但没有改善自我报告的他汀类药物依从性。
BACKGROUND: Outcomes of tailoring statin-type based on solute carrier organic anion transporterfamily member 1B1 (SLCO1B1)pharmacogenetic toxicity information on patient, provider, and pharmacological outcomes are unknown.METHODS: The trial randomized 159 patients not taking statins because of prior statin myalgia 1:1 to receiving SLCO1B1 GIST (Genotype Informed Statin Therapy) versus usual care (UC) and followed for up to 8 months. The UC arm received their SLCO1B1 results post-trial. The primary outcome was statin adherence using the Morisky Medication Adherence Scale, which was assessed in those patients who reinitiated statins. Secondary outcomes assessed in all participants included statin reinitiation and LDLc (low-density lipoprotein cholesterol), within and post-trial. Using commercial laboratory data, serial LDLc were compared between 1907 patients receiving SLCO1B1 testing and propensity-matched, untested controls.RESULTS: Trial participants were 25% SLCO1B1*5 carriers. Statin adherence was similar between arms (Morisky Medication Adherence Scale in GIST versus UC, 6.8 +/- 1.5 versus 6.9 +/- 1.6, P=0.96). GIST led to more new statin prescriptions (55.4% versus 38.0%, P=0.04) and lower LDLc at 3 months (131.9 +/- 42.0 versus 144.4 +/- 43.0 mg/dL; P=0.048) with similar magnitude at 8 months (128.6 +/- 37.9 versus 141.0 +/- 44.4; P=0.12). SLCO1B1*5 carriers exhibited a greater drop in LDLc with GIST versus UC (interaction P=0.048). Post-trial, LDLc decreased in UC participants who crossed over to GIST compared with those allocated to GIST (-14.9 +/- 37.8 versus +9.0 +/- 37.3 mg/dL, P=0.03). Patients tested for SLCO1B1 though a commercial laboratory had a greater LDLc decrease (P=0.04) compared with controls.CONCLUSIONS: Delivery of SLCO1B1 pharmacogenetic testing that addresses statin myalgia improved statin reinitiation and LDLc but did not improve self-reported statin adherence.