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SLCO1B1*5 Allele Is Associated With Atorvastatin Discontinuation and Adverse Muscle Symptoms in the Context of Routine Care
Author(s) -
Voora Deepak,
Baye Jordan,
McDermaid Adam,
Narayana Gowda Smitha,
Wilke Russell A.,
Nicole Myrmoe Anna,
Hajek Catherine,
Larson Eric A.
Publication year - 2022
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.2527
Subject(s) - atorvastatin , hazard ratio , discontinuation , medicine , odds ratio , slco1b1 , context (archaeology) , cohort , proportional hazards model , confidence interval , statin , pharmacogenetics , genotype , biology , genetics , gene , paleontology
The SLCO1B1 genotype is known to influence patient adherence to statin therapy, in part by increasing the risk for statin‐associated musculoskeletal symptoms (SAMSs). The SLCO1B1*5 allele has previously been associated with simvastatin discontinuation and SAMSs. Prior analyses of the relationship between SLCO1B1*5 and atorvastatin muscle side effects have been inconclusive due to insufficient power. We now quantify the impact of SLCO1B1*5 on atorvastatin discontinuation and SAMSs in a large observational cohort using electronic medical record data from a single health care system. In our study cohort ( n = 1,627 patients exposed to atorvastatin during the course of routine clinical care), 56% ( n = 912 of 1,627 patients) discontinued atorvastatin and 18% ( n = 303 of 1,627 patients) developed SAMSs. A univariate model revealed that SLCO1B1*5 increased the likelihood that patients would stop atorvastatin during routine care (odds ratio 1.2; 95% confidence interval (CI), 1.1–1.5; P = 0.04). A multivariate Cox proportional hazards model further demonstrated that this same variant was associated with time to atorvastatin discontinuation (hazard ratio 1.2; 95% CI, 1.1–1.4; P = 0.004). Additional time‐to‐event analyses also revealed that SCLO1B1*5 was associated with SAMSs (hazard ratio 1.4; 95% CI, 1.1–1.7; P = 0.02). Atorvastatin discontinuation was associated with SAMSs (odds ratio 1.67; P = 0.0001) in our cohort.