IMPORTANCE Nonadherence to statin guidelines is common. The solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotype is associated with simvastatin myopathy risk and is proposed for clinical implementation. The unintended harms of using pharmacogenetic information to guide pharmacotherapy remain a concern for some stakeholders. OBJECTIVETo determine the impact of delivering SLCO1B1 pharmacogenetic results to physicians on the effectiveness of atherosclerotic cardiovascular disease (ASCVD) prevention (measured by low-density lipoprotein cholesterol [LDL-C] levels) and concordance with prescribing guidelines for statin safety and effectiveness. DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial was performed from December 2015 to July 2019 at 8 primary care practices in the Veterans Affairs Boston Healthcare System. Participants included statin-naive patients with elevated ASCVD risk. Data analysis was performed from October 2019 to September 2020. INTERVENTIONS SLCO1B1 genotyping and results reporting to primary care physicians at baseline (intervention group) vs after 1 year (control group). MAIN OUTCOMES AND MEASURES The primary outcome was the 1-year change in LDL-C level. The secondary outcomes were 1-year concordance with American College of Cardiology-American Heart Association and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for statin therapy and statin-associated muscle symptoms (SAMS). RESULTS Among 408 patients (mean [SD] age, 64.1 [7.8] years; 25 women [6.1%]), 193 were randomized to the intervention group and 215 were randomized to the control group. Overall, 120 participants (29%) had a SLCO1B1 genotype indicating increased simvastatin myopathy risk. Physicians offered statin therapy to 65 participants (33.7%) in the intervention group and 69 participants (32.1%) in the control group. Compared with patients whose physicians did not know their SLCO1B1 results at baseline, patients whose physicians received the results had noninferior reductions in LDL-C at 12 months (mean [SE] change in LDL-C, −1.1 [1.2] mg/dL in the intervention group and −2.2 [1.3] mg/dL in the control group; difference, −1.1 mg/dL; 90% CI, −4.1 to 1.8 mg/dL; P < .001 for noninferiority margin of 10 mg/dL). The proportion of patients with American College of Cardiology-American Heart Association guideline-concordant statin prescriptions in the intervention group was noninferior to that in the control group (12 patients [6.2%] vs 14 patients [6.5%]; difference, −0.003; 90% CI, −0.038 to 0.032; P < .001 for noninferiority margin of 15%). All patients in both groups were concordant with CPIC guidelines for safe statin prescribing. Physicians (continued) Key Points Question Can pharmacogenetic results for statin myopathy risk be used clinically without the unintended harms of statin avoidance or underdosing? Findings In this randomized clinical trial including 408 patients, statin-naive patients whose physicians knew their SLCO1B1 genotype results at baseline did not have poore...

Demonstrated improvements in patient outcomes will facilitate the clinical implementation of pharmacogenetic testing. Using the association between solute carrier organic anion transporter family member 1B1 (SLCO1B1) and statin-associated muscle symptoms (SAMSs) as a model, we conducted a systematic review of patient outcomes after delivery of SLCO1B1 results. Using PubMed and Embase searches through December 19, 2017, we identified 37 eligible records reporting preliminary or final outcomes, including six studies delivering only SLCO1B1 results and five large healthcare system-based implementation projects of multipharmacogene panels. Two small trials have demonstrated at least short-term improvements in low-density lipoprotein cholesterol after SLCO1B1 testing among previously statin intolerant patients. Evidence from large implementation projects suggests that SLCO1B1 results may change prescribing patterns for some high-risk patients. No study has reported improvements in SAMSs or cardiovascular events or tracked the economic outcomes of SLCO1B1 testing. Ongoing studies should collect and report outcomes relevant to pharmacogenetics stakeholders.

This study documents trends in risk-adjusted quality and cost for a variety of surgical procedures, and explores innovation in treatment among Medicare beneficiaries from 2002 through 2011. Methods: We consider 11 classes of surgery, characterized by AHRQ's Clinical Classification System; the surgical classes studied range from tracheostomy to heart valve procedures to colorectal resection to wound debridement. For each surgical class, we assess trends in treatment costs and health outcomes among Medicare beneficiaries receiving these procedures during hospital stays. Quality was defined as rate of 30-day survival with the avoidance of unplanned readmissions, while costs include hospital costs and concurrent physician and ancillary services. Quality and costs are adjusted for patient severity based on demographics, comorbidity, and community context. Surgical innovations are operationalized as clinically distinctive procedures with nonexistent or limited use in 2002, identified using ICD-9 procedure codes. Results: Analysis found significant and positive quality growth for 6 surgical classes: heart valve procedures (3.49%), CABG (2.00%), gastrostomy (5.32%), tracheostomy (5.01%), wound debridement (2.78%), and excision of lysis peritoneal adhesions (1.68%). Preliminary analysis also found significant and negative cost trends for 3 surgical classes: tracheostomy (-15.05%), PTCA (-11.11%) and wound debridement (-9.69%). In addition, significant cost increases were observed for gastrostomy (5.51%), colorectal resection (4.06 %), and exploratory laparotomy (30.72 %). Substantial treatment innovation occurred with respect to surgical procedures utilized for colorectal resection. Conclusions: In 2 out of 11 surgical classes, the quality of surgical care improved while treatment costs declined. Four other surgical classes exhibited either a cost decrease or quality improvement. While cost increased for 3 other surgical classes, only 1 of them was associated with improved quality of care. In the remaining 2 surgical classes, there was no significant change in quality or cost. These trends were associated with measurable innovation in treatment for only one surgical class.

No abstract