Effect of Pharmacogenetic Testing for Statin Myopathy Risk vs Usual Care on Blood Cholesterol A Randomized Clinical Trial

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 poorer low-density lipoprotein cholesterol reductions after 1 year, compared with patients who received usual care. Meaning Although these findings do not support the widespread adoption of stand-alone preemptive SLCO1B1 genotype testing, they may allay stakeholder concerns about the potential unintended harms of the clinical use of such information. This randomized clinical trial examines the impact of delivering SLCO1B1 pharmacogenetic results to physicians on low-density lipoprotein cholesterol levels and concordance with prescribing guidelines for statin safety and effectiveness. 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. Objective To 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 interventio