SLCO1B15 Allele Is Associated With Atorvastatin Discontinuation and Adverse Muscle Symptoms in the Context of Routine Care

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 be...

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Veröffentlicht in:Clinical pharmacology and therapeutics 2022-05, Vol.111 (5), p.1075-1083
Hauptverfasser: Voora, Deepak, Baye, Jordan, McDermaid, Adam, Narayana Gowda, Smitha, Wilke, Russell A., Nicole Myrmoe, Anna, Hajek, Catherine, Larson, Eric A.
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container_end_page 1083
container_issue 5
container_start_page 1075
container_title Clinical pharmacology and therapeutics
container_volume 111
creator Voora, Deepak
Baye, Jordan
McDermaid, Adam
Narayana Gowda, Smitha
Wilke, Russell A.
Nicole Myrmoe, Anna
Hajek, Catherine
Larson, Eric A.
description 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.
doi_str_mv 10.1002/cpt.2527
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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). 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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). 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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.</abstract><cop>United States</cop><pub>John Wiley and Sons Inc</pub><pmid>35034348</pmid><doi>10.1002/cpt.2527</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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ispartof Clinical pharmacology and therapeutics, 2022-05, Vol.111 (5), p.1075-1083
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subjects Alleles
Atorvastatin - adverse effects
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects
Liver-Specific Organic Anion Transporter 1 - genetics
Muscles
Polymorphism, Single Nucleotide
Pyrroles - therapeutic use
Simvastatin - adverse effects
title SLCO1B15 Allele Is Associated With Atorvastatin Discontinuation and Adverse Muscle Symptoms in the Context of Routine Care
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