Literature DB >> 30354330

Effects of Delivering SLCO1B1 Pharmacogenetic Information in Randomized Trial and Observational Settings.

Bruce Peyser1, Emily P Perry2, Kavisha Singh1, Rosalynn D Gill3, Michael R Mehan3, Susanne B Haga4, Michael D Musty4, Nicholas A Milazzo2, Dillon Savard2, Yi-Ju Li2, Gloria Trujilio1, Deepak Voora1,4.   

Abstract

BACKGROUND: Outcomes of tailoring statin-type based on solute carrier organic anion transporterfamily member 1B1 ( SLCO1B1)pharmacogenetic toxicity information on patient, provider, and pharmacological outcomes are unknown.
METHODS: The trial randomized 159 patients not taking statins because of prior statin myalgia 1:1 to receiving SLCO1B1 GIST (Genotype Informed Statin Therapy) versus usual care (UC) and followed for up to 8 months. The UC arm received their SLCO1B1 results post-trial. The primary outcome was statin adherence using the Morisky Medication Adherence Scale, which was assessed in those patients who reinitiated statins. Secondary outcomes assessed in all participants included statin reinitiation and LDLc (low-density lipoprotein cholesterol), within and post-trial. Using commercial laboratory data, serial LDLc were compared between 1907 patients receiving SLCO1B1 testing and propensity-matched, untested controls.
RESULTS: Trial participants were 25% SLCO1B1*5 carriers. Statin adherence was similar between arms (Morisky Medication Adherence Scale in GIST versus UC, 6.8±1.5 versus 6.9±1.6, P=0.96). GIST led to more new statin prescriptions (55.4% versus 38.0%, P=0.04) and lower LDLc at 3 months (131.9±42.0 versus 144.4±43.0 mg/dL; P=0.048) with similar magnitude at 8 months (128.6±37.9 versus 141.0±44.4; P=0.12). SLCO1B1*5 carriers exhibited a greater drop in LDLc with GIST versus UC (interaction P=0.048). Post-trial, LDLc decreased in UC participants who crossed over to GIST compared with those allocated to GIST (-14.9±37.8 versus +9.0±37.3 mg/dL, P=0.03). Patients tested for SLCO1B1 though a commercial laboratory had a greater LDLc decrease ( P=0.04) compared with controls.
CONCLUSIONS: Delivery of SLCO1B1 pharmacogenetic testing that addresses statin myalgia improved statin reinitiation and LDLc but did not improve self-reported statin adherence. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01894230.

Entities:  

Keywords:  SLCO1B1 protein; clinical trial; genotype; hydroxymethylglutaryl-CoA reductase inhibitors; myalgia; patients; pharmacogenetics

Mesh:

Substances:

Year:  2018        PMID: 30354330     DOI: 10.1161/CIRCGEN.118.002228

Source DB:  PubMed          Journal:  Circ Genom Precis Med        ISSN: 2574-8300


  17 in total

Review 1.  Genetics, Dyslipidemia, and Cardiovascular Disease: New Insights.

Authors:  Ricardo Stein; Filipe Ferrari; Fernando Scolari
Journal:  Curr Cardiol Rep       Date:  2019-06-21       Impact factor: 2.931

2.  The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms.

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Journal:  Clin Pharmacol Ther       Date:  2022-03-11       Impact factor: 6.903

3.  The Integrating Pharmacogenetics in Clinical Care (I-PICC) Study: Protocol for a point-of-care randomized controlled trial of statin pharmacogenetics in primary care.

Authors:  Jason L Vassy; Charles A Brunette; Nilla Majahalme; Sanjay Advani; Lauren MacMullen; Cynthia Hau; Andrew J Zimolzak; Stephen J Miller
Journal:  Contemp Clin Trials       Date:  2018-10-24       Impact factor: 2.226

4.  Pharmacogenomic-Based Decision Support to Predict Adherence to Medications.

Authors:  Carlton Christian; Brittany A Borden; Keith Danahey; Kiang-Teck J Yeo; Xander M R van Wijk; Mark J Ratain; Peter H O'Donnell
Journal:  Clin Pharmacol Ther       Date:  2020-05-25       Impact factor: 6.875

Review 5.  Pharmacogenetics to guide cardiovascular drug therapy.

Authors:  Julio D Duarte; Larisa H Cavallari
Journal:  Nat Rev Cardiol       Date:  2021-05-05       Impact factor: 32.419

6.  Preferences for and acceptability of receiving pharmacogenomic results by mail: A focus group study with a primarily African-American cohort.

Authors:  Priscilla A Chan; Katie L Lewis; Barbara B Biesecker; Lori H Erby; Grace-Ann Fasaye; Sandra Epps; Leslie G Biesecker; Erin Turbitt
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7.  Opportunity for Genotype-Guided Prescribing Among Adult Patients in 11 US Health Systems.

Authors:  J Kevin Hicks; Nihal El Rouby; Henry H Ong; Jonathan S Schildcrout; Laura B Ramsey; Yaping Shi; Leigh Anne Tang; Christina L Aquilante; Amber L Beitelshees; Kathryn V Blake; James J Cimino; Brittney H Davis; Philip E Empey; David P Kao; Daniel L Lemkin; Nita A Limdi; Gloria P Lipori; Marc B Rosenman; Todd C Skaar; Evgenia Teal; Sony Tuteja; Laura K Wiley; Helen Williams; Almut G Winterstein; Sara L Van Driest; Larisa H Cavallari; Josh F Peterson
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8.  Pragmatic Trials in Genomic Medicine: The Integrating Pharmacogenetics In Clinical Care (I-PICC) Study.

Authors:  Charles A Brunette; Stephen J Miller; Nilla Majahalme; Cynthia Hau; Lauren MacMullen; Sanjay Advani; Sophie A Ludin; Andrew J Zimolzak; Jason L Vassy
Journal:  Clin Transl Sci       Date:  2019-12-18       Impact factor: 4.689

Review 9.  Evidence to Support Inclusion of Pharmacogenetic Biomarkers in Randomised Controlled Trials.

Authors:  Danielle Johnson; Dyfrig Hughes; Munir Pirmohamed; Andrea Jorgensen
Journal:  J Pers Med       Date:  2019-09-01

10.  Genomewide Association Study of Statin-Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink.

Authors:  Daniel F Carr; Ben Francis; Andrea L Jorgensen; Eunice Zhang; Hector Chinoy; Susan R Heckbert; Joshua C Bis; Jennifer A Brody; James S Floyd; Bruce M Psaty; Mariam Molokhia; Maryse Lapeyre-Mestre; Anita Conforti; Ana Alfirevic; Tjeerd van Staa; Munir Pirmohamed
Journal:  Clin Pharmacol Ther       Date:  2019-07-31       Impact factor: 6.875

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