VA Boston Healthcare System, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Boston, MA, USA.
VA Boston Healthcare System, Boston, MA, USA.
Contemp Clin Trials. 2018 Dec;75:40-50. doi: 10.1016/j.cct.2018.10.010. Epub 2018 Oct 24.
The association between the SLCO1B1 rs4149056 variant and statin-associated muscle symptoms (SAMS) is well validated, but the clinical utility of its implementation in patient care is unknown.
The Integrating Pharmacogenetics in Clinical Care (I-PICC) Study is a pseudo-cluster randomized controlled trial of SLCO1B1 genotyping among statin-naïve primary care and women's health patients across the Veteran Affairs Boston Healthcare System. Eligible patients of enrolled primary care providers are aged 40-75 and have elevated risk of cardiovascular disease by American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Patients give consent by telephone in advance of an upcoming appointment, but they are enrolled only if and when their provider co-signs an order for SLCO1B1 testing, performed on a blood sample already collected in clinical care. Enrolled patients are randomly allocated to have their providers receive results through the electronic health record at baseline (PGx + arm) versus after 12 months (PGx- arm). The primary outcome is the change in low-density lipoprotein cholesterol (LDL-C) after one year. Secondary outcomes are concordance with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for simvastatin prescribing, concordance with ACC/AHA guidelines for statin use, and incidence of SAMS. With 408 patients, the study has >80% power to exclude a between-group LDL-C difference of 10 mg/dL (non-inferiority design) and to detect between-group differences of 15% in CPIC guideline concordance (superiority design).
The outcomes of the I-PICC Study will inform the clinical utility of preemptive SLCO1B1 testing in the routine practice of medicine, including its proposed benefits and unforeseen risks.
SLCO1B1 rs4149056 变异与他汀类药物相关肌肉症状（SAMS）之间的关联已得到充分验证，但该变异在患者护理中的临床应用价值尚不清楚。
Integrating Pharmacogenetics in Clinical Care（I-PICC）研究是一项在退伍军人事务部波士顿医疗保健系统中的初级保健和妇女健康患者中进行 SLCO1B1 基因分型的伪聚类随机对照试验。符合条件的患者为年龄在 40-75 岁之间的初级保健提供者的患者，且根据美国心脏病学会/美国心脏协会（ACC/AHA）指南具有较高的心血管疾病风险。患者在预约前通过电话提前同意，但只有在其提供者共同签署 SLCO1B1 检测订单时才会登记，该订单是在临床护理中已经采集的血液样本上进行的。登记的患者被随机分配，让他们的提供者在基线时（PGx+臂）或 12 个月后（PGx-臂）通过电子健康记录获得结果。主要结局是一年后低密度脂蛋白胆固醇（LDL-C）的变化。次要结局是与临床药物基因组学实施联盟（CPIC）辛伐他汀处方指南的一致性、与 ACC/AHA 他汀类药物使用指南的一致性以及 SAMS 的发生率。该研究纳入 408 例患者，具有 >80%的效能排除组间 LDL-C 差异 10mg/dL（非劣效性设计），并可检测组间 CPIC 指南一致性差异 15%（优效性设计）。
I-PICC 研究的结果将为在常规医学实践中进行预防性 SLCO1B1 检测的临床应用价值提供信息，包括其预期的益处和意想不到的风险。
