SLCO1B1 gene-based clinical decision support reduces statin-associated muscle symptoms risk with simvastatin
Abstract
Background:SLCO1B1 variants are known to be a strong predictor of statin-associated muscle symptoms (SAMS) risk with simvastatin. Methods: The authors conducted a retrospective chart review on 20,341 patients who had SLCO1B1 genotyping to quantify the uptake of clinical decision support (CDS) for genetic variants known to impact SAMS risk. Results: A total of 182 patients had 417 CDS alerts generated, and 150 of these patients (82.4%) received pharmacotherapy that did not increase risks for SAMS. Providers were more likely to cancel simvastatin orders in response to CDS alerts if genotyping had been done prior to the first simvastatin prescription than after (94.1% vs 28.5%, respectively; p < 0.001). Conclusion: CDS significantly reduces simvastatin prescribing at doses associated with SAMS.
Papers of special note have been highlighted as: • of interest
References
- 1. . Temporal trends in the remaining lifetime risk of cardiovascular disease among middle-aged adults across 6 decades: the Framingham Study. Circulation 145(17), 1324–1338 (2022).
- 2. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: A Systematic Review for the U.S. Preventive Services Task Force. Pacific Northwest Evidence-Based Practice Center, OR, USA (2022).
- 3. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J. Am. Coll. Cardiol. 74(10), 1376–1414 (2019).
- 4. The SLCO1B1*5 genetic variant is associated with statin-induced side effects. J. Am. Coll. Cardiol. 54(17), 1609–1616 (2009).
- 5. Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction. Eur. Heart J. 27(10), 1153–1158 (2006).
- 6. . Adherence to statins, beta-blockers and angiotensin-converting enzyme inhibitors following a first cardiovascular event: a retrospective cohort study. Can. J. Cardiol. 21(6), 485–488 (2005).
- 7. A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study. Lancet 401(10374), 347–356 (2023). • Preemptive pharmacogenomic testing significantly decreased adverse effects.
- 8. Progression of precision statin prescribing for reduction of statin-associated muscle symptoms. Pharmacogenomics 23(10), 585–596 (2022). • SLCO1B1 testing can help mitigate risk for developing statin-associated muscle symptoms.
- 9. The Clinical Pharmacogenetics Implementation Consortium guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and statin-associated musculoskeletal symptoms. Clin. Pharmacol. Ther. 111(5), 1007–1021 (2022).
- 10. Effects of delivering SLCO1B1 pharmacogenetic information in randomized trial and observational settings. Circ. Genom. Precis. Med. 11(9), e002228 (2018).
- 11. . Pharmacogenetics of statin-induced myotoxicity. Front. Genet. 11, 575678 (2020).
- 12. Merck. ZOCOR (simvastatin) Tablets. Initial U.S. Approval: 1991 Merck Sharp & Dohme Ltd (2012).
- 13. Common nonsynonymous substitutions in SLCO1B1 predispose to statin intolerance in routinely treated individuals with Type 2 diabetes: a go-DARTS study. Clin. Pharmacol. Ther. 89(2), 210–216 (2011).
- 14. . Outcomes in 45 patients with statin-associated myopathy. Arch. Intern. Med. 165(22), 2671–2676 (2005).
- 15. . Statin-induced rhabdomyolysis: a comprehensive review of case reports. Physiother. Can. 66(2), 124–132 (2014).
- 16. . Statin-induced myopathy: a review and update. Expert Opin. Drug Saf. 10(3), 373–387 (2011).
- 17. Implementation of wide-scale pharmacogenetic testing in primary care. Pharmacogenomics 20(12), 903–913 (2019).
- 18. The Pharmacogenomics Research Network Translational Pharmacogenetics Program: overcoming challenges of real-world implementation. Clin. Pharmacol. Ther. 94(2), 207–210 (2013).
- 19. . Implementing pharmacogenomics at your institution: establishment and overcoming implementation challenges. Clin. Transl. Sci. 9(5), 233–245 (2016).
- 20. . Biomedical data science and informatics challenges to implementing pharmacogenomics with electronic health records. Annu. Rev. Biomed. Data Sci. 289–314 (2020).
- 21. Integrating pharmacogenomics into the electronic health record by implementing genomic indicators. J. Am. Med. Inform. Assoc. 27(1), 154–158 (2020).
- 22. Physician response to implementation of genotype-tailored antiplatelet therapy. Clin. Pharmacol. Ther. 100(1), 67–74 (2016).
- 23. Clinical pharmacogenetics implementation: approaches, successes, and challenges. Am. J. Med. Genet. C Semin. Med. Genet. 166c(1), 56–67 (2014).
- 24. Prescriber adoption of SLCO1B1 genotype-guided simvastatin clinical decision support in a clinical pharmacogenetics program. Clin. Pharmacol. Ther. 113(2), 321–327 (2023). • Providers with pharmacogenomic training were significantly more likely to accept clinical decision support for genetic guided simvastatin prescribing.
- 25. Impact of automated best practice advisories on provider response to CYP2C19 genotyping results for patients on clopidogrel. J. Pharm. Pract. 36(3), 487–493 (2023).
- 26. Clinician adherence to pharmacogenomics prescribing recommendations in clinical decision support alerts. J. Am. Med. Inform. Assoc. 30(1), 132–138 (2022).
- 27. Pharmacogenomics-based point-of-care clinical decision support significantly alters drug prescribing. Clin. Pharmacol. Ther. 102(5), 859–869 (2017).
- 28. . Pharmacogenomic clinical decision support: a scoping review. Clin. Pharmacol. Ther. 113(4), 803–815 (2023).
- 29. Precision population medicine in primary care: the Sanford Chip experience. Front. Genet. 12(274), 626845 (2021).
- 30. Improved provider preparedness through an 8-part genetics and genomic education program. Genet. Med. 24(1), 214–224 (2022).
- 31. . Integration of genomics in primary care.. Am. J. Med. 128(11), 1251.e1251–1255 (2015).
- 32. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. Circulation 139(25), e1082–e1143 (2019).
- 33. . Akaike's information criterion in generalized estimating equations. Biometrics 57(1), 120–125 (2001).
- 34. R Core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria (2017).
- 35. Benefit of preemptive pharmacogenetic information on clinical outcome. Clin. Pharmacol. Ther. 103(5), 787–794 (2018).
- 36. . Preemptive panel-based pharmacogenetic testing: the time is now. Pharm. Res. 34(8), 1551–1555 (2017).
- 37. Preemptive pharmacogenomic testing for precision medicine: a comprehensive analysis of five actionable pharmacogenomic genes using next-generation DNA sequencing and a customized CYP2D6 genotyping cascade. J. Mol. Diagn. 18(3), 438–445 (2016).
- 38. . Evolving health care through personal genomics. Nat. Rev. Genet. 18(4), 259–267 (2017).
- 39. . Researchers and policymakers point to successes and challenges in personalized medicine. In: American Association for the Advancement of Science (AAAS). (2009). https://www.aaas.org/news/researchers-and-policymakers-point-successes-and-challenges-personalized-medicine
- 40. SLCO1B1 variants and statin-induced myopathy – a genomewide study. N. Engl. J. Med. 359(8), 789–799 (2008).
- 41. . Intolerance to statins: mechanisms and management. Diabetes Care 36(Suppl. 2), S325–S330 (2013).
- 42. . Statin induced myopathy. BMJ 337, a2286 (2008).
- 43. . Improving medication-related clinical decision support. Am. J. Health Syst. Pharm. 75(4), 239–246 (2018).
- 44. Integrating clinical decision support systems for pharmacogenomic testing into clinical routine – a scoping review of designs of user-system interactions in recent system development. BMC Med. Inform. Decis. Mak. 17(1), 81 (2017).
- 45. . Reduced effectiveness of interruptive drug–drug interaction alerts after conversion to a commercial electronic health record. J. Gen. Intern. Med. 33(11), 1868–1876 (2018).
- 46. SLCO1B1*5 allele is associated with atorvastatin discontinuation and adverse muscle symptoms in the context of routine care. Clin. Pharmacol. Ther. 111(5), 1075–1083 (2022). • Genetic variants in SLCO1B1 have been linked to patient discontinuation of atorvastatin and adverse effects.
- 47. Adoption of pharmacogenomic testing by US physicians: results of a nationwide survey. Clin. Pharmacol. Ther. 91(3), 450–458 (2012).
- 48. . Primary care physicians' knowledge of and experience with pharmacogenetic testing. Clin. Genet. 82(4), 388–394 (2012).
- 49. Assessment of primary care practitioners' attitudes and interest in pharmacogenomic testing. Pharmacogenomics 21(15), 1085–1094 (2020).
- 50. . Patient and health care provider needs and preferences in understanding pharmacogenomic and genomic testing: a meta-data analysis. Qual. Health Res. 30(1), 43–59 (2020).
- 51. Integrating pharmacogenomics into clinical practice: promise vs reality. Am. J. Med. 129(10), 1093–1099.e1091 (2016).
- 52. Warning Letter, Inova Genomics Laboratory. US FDA, Silver Spring, MD, USA (2019).
- 53. . Systematic review for the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J. Am. Coll. Cardiol. 73(24), 3210–3227 (2019).
- 54. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 139(25), e1082–e1143 (2019).
- 55. FDA Drug Safety Communication: New Restrictions, Contraindications, and Dose Limitations for Zocor (Simvastatin) to Reduce the Risk of Muscle Injury. US FDA, Silver Spring, MD, USA (2017).