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 |
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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). Atorvastatin discontinuation was associated with SAMSs (odds ratio 1.67; P = 0.0001) in our cohort.</description><identifier>ISSN: 0009-9236</identifier><identifier>EISSN: 1532-6535</identifier><identifier>DOI: 10.1002/cpt.2527</identifier><identifier>PMID: 35034348</identifier><language>eng</language><publisher>United States: John Wiley and Sons Inc</publisher><subject>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</subject><ispartof>Clinical pharmacology and therapeutics, 2022-05, Vol.111 (5), p.1075-1083</ispartof><rights>2022 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.</rights><rights>2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4107-78174b256d7213aac95f8b1c554ecd439b6c7e05c19d5aac069a163ed89207c23</citedby><cites>FETCH-LOGICAL-c4107-78174b256d7213aac95f8b1c554ecd439b6c7e05c19d5aac069a163ed89207c23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcpt.2527$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcpt.2527$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,315,781,785,886,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35034348$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Voora, Deepak</creatorcontrib><creatorcontrib>Baye, Jordan</creatorcontrib><creatorcontrib>McDermaid, Adam</creatorcontrib><creatorcontrib>Narayana Gowda, Smitha</creatorcontrib><creatorcontrib>Wilke, Russell A.</creatorcontrib><creatorcontrib>Nicole Myrmoe, Anna</creatorcontrib><creatorcontrib>Hajek, Catherine</creatorcontrib><creatorcontrib>Larson, Eric A.</creatorcontrib><title>SLCO1B15 Allele Is Associated With Atorvastatin Discontinuation and Adverse Muscle Symptoms in the Context of Routine Care</title><title>Clinical pharmacology and therapeutics</title><addtitle>Clin Pharmacol Ther</addtitle><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.</description><subject>Alleles</subject><subject>Atorvastatin - adverse effects</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects</subject><subject>Liver-Specific Organic Anion Transporter 1 - genetics</subject><subject>Muscles</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Pyrroles - therapeutic use</subject><subject>Simvastatin - adverse effects</subject><issn>0009-9236</issn><issn>1532-6535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp1kV1P2zAUhq0JtBY2ab9g8uVuUvwRJ_ENUpYNqFTENDrt0nKd0zUoiYvtFMqvxwVWwQVX9vF5_BzLL0JfKJlQQtiJWYcJEyz_gMZUcJZkgosDNCaEyEQyno3Qkfc3sUxlUXxEIy4IT3lajNHD9ay6ot-pwGXbQgt46nHpvTWNDlDjv01Y4TJYt9E-6ND0-Efjje3jboil7bHua1zWG3Ae8OXgTVRcb7t1sJ3HEQ8rwFXk4T5gu8S_7RCvxiPt4BM6XOrWw-eX9Rj9Ofs5ry6S2dX5tCpniUkpyZO8oHm6YCKrc0a51kaKZbGgRogUTJ1yuchMDkQYKmsR2ySTmmYc6kIykhvGj9Hps3c9LDqoDfTB6VatXdNpt1VWN-ptp29W6p_dKMkJF3In-PYicPZ2AB9UFz8B2lb3YAevWBYH5YREfI8aZ713sNyPoUTtolIxKrWLKqJfXz9rD_7PJgLJM3DXtLB9V6SqX_Mn4SOVeZ5X</recordid><startdate>202205</startdate><enddate>202205</enddate><creator>Voora, Deepak</creator><creator>Baye, Jordan</creator><creator>McDermaid, Adam</creator><creator>Narayana Gowda, Smitha</creator><creator>Wilke, Russell A.</creator><creator>Nicole Myrmoe, Anna</creator><creator>Hajek, Catherine</creator><creator>Larson, Eric A.</creator><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>202205</creationdate><title>SLCO1B15 Allele Is Associated With Atorvastatin Discontinuation and Adverse Muscle Symptoms in the Context of Routine Care</title><author>Voora, Deepak ; Baye, Jordan ; McDermaid, Adam ; Narayana Gowda, Smitha ; Wilke, Russell A. ; Nicole Myrmoe, Anna ; Hajek, Catherine ; Larson, Eric A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4107-78174b256d7213aac95f8b1c554ecd439b6c7e05c19d5aac069a163ed89207c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Alleles</topic><topic>Atorvastatin - adverse effects</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects</topic><topic>Liver-Specific Organic Anion Transporter 1 - genetics</topic><topic>Muscles</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Pyrroles - therapeutic use</topic><topic>Simvastatin - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Voora, Deepak</creatorcontrib><creatorcontrib>Baye, Jordan</creatorcontrib><creatorcontrib>McDermaid, Adam</creatorcontrib><creatorcontrib>Narayana Gowda, Smitha</creatorcontrib><creatorcontrib>Wilke, Russell A.</creatorcontrib><creatorcontrib>Nicole Myrmoe, Anna</creatorcontrib><creatorcontrib>Hajek, Catherine</creatorcontrib><creatorcontrib>Larson, Eric A.</creatorcontrib><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Voora, Deepak</au><au>Baye, Jordan</au><au>McDermaid, Adam</au><au>Narayana Gowda, Smitha</au><au>Wilke, Russell A.</au><au>Nicole Myrmoe, Anna</au><au>Hajek, Catherine</au><au>Larson, Eric A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SLCO1B15 Allele Is Associated With Atorvastatin Discontinuation and Adverse Muscle Symptoms in the Context of Routine Care</atitle><jtitle>Clinical pharmacology and therapeutics</jtitle><addtitle>Clin Pharmacol Ther</addtitle><date>2022-05</date><risdate>2022</risdate><volume>111</volume><issue>5</issue><spage>1075</spage><epage>1083</epage><pages>1075-1083</pages><issn>0009-9236</issn><eissn>1532-6535</eissn><abstract>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.</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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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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