title: Evidence for Clinical Implementation of Pharmacogenomics in Cardiac Drugs.
abstract: OBJECTIVE
  To comprehensively assess the pharmacogenomic evidence of routinely used drugs for clinical utility.
  
  
  METHODS
  Between January 2, 2011, and May 31, 2013, we assessed 71 drugs by identifying all drug/genetic variant combinations with published clinical pharmacogenomic evidence. Literature supporting each drug/variant pair was assessed for study design and methods, outcomes, statistical significance, and clinical relevance. Proposed clinical summaries were formally scored using a modified AGREE (Appraisal of Guidelines for Research and Evaluation) II instrument, including recommendation for or against guideline implementation.
  
  
  RESULTS
  Positive pharmacogenomic findings were identified for 51 of 71 cardiovascular drugs (71.8%), representing 884 unique drug/variant pairs from 597 publications. After analysis for quality and clinical relevance, 92 drug/variant pairs were proposed for translation into clinical summaries, encompassing 23 drugs (32.4% of drugs reviewed). All were recommended for clinical implementation using AGREE II, with mean ± SD overall quality scores of 5.18±0.91 (of 7.0; range, 3.67-7.0). Drug guidelines had highest mean ± SD scores in AGREE II domain 1 (Scope) (91.9±6.1 of 100) and moderate but still robust mean ± SD scores in domain 3 (Rigor) (73.1±11.1), domain 4 (Clarity) (67.8±12.5), and domain 5 (Applicability) (65.8±10.0). Clopidogrel (CYP2C19), metoprolol (CYP2D6), simvastatin (rs4149056), dabigatran (rs2244613), hydralazine (rs1799983, rs1799998), and warfarin (CYP2C9/VKORC1) were distinguished by the highest scores. Seven of the 9 most commonly prescribed drugs warranted translation guidelines summarizing clinical pharmacogenomic information.
  
  
  CONCLUSIONS
  Considerable clinically actionable pharmacogenomic information for cardiovascular drugs exists, supporting the idea that consideration of such information when prescribing is warranted.
authors.affiliation: Pritzker School of Medicine, The University of Chicago, Chicago, IL.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Kaufman
authors.affiliation: Center for Personalized Therapeutics, The University of Chicago, Chicago, IL.
authors.forename: Jared
authors.initials: J
authors.lastname: Spitz
authors.affiliation: Center for Personalized Therapeutics, The University of Chicago, Chicago, IL.
authors.forename: Michael
authors.initials: M
authors.lastname: Jacobs
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL.
authors.forename: Matthew
authors.initials: M
authors.lastname: Sorrentino
authors.affiliation: Center for Personalized Therapeutics, The University of Chicago, Chicago, IL.
authors.forename: Shennin
authors.initials: S
authors.lastname: Yuen
authors.affiliation: Center for Research Informatics, The University of Chicago, Chicago, IL.
authors.forename: Keith
authors.initials: K
authors.lastname: Danahey
authors.affiliation: Center for Research Informatics, The University of Chicago, Chicago, IL.
authors.forename: Donald
authors.initials: D
authors.lastname: Saner
authors.affiliation: Department of Genetics, Stanford University, Palo Alto, CA.
authors.forename: Teri E
authors.initials: TE
authors.lastname: Klein
authors.affiliation: Department of Genetics, Stanford University, Palo Alto, CA; Department of Bioengineering, Stanford University, Palo Alto, CA; Department of Medicine, Stanford University, Palo Alto, CA.
authors.forename: Russ B
authors.initials: RB
authors.lastname: Altman
authors.affiliation: Center for Personalized Therapeutics, The University of Chicago, Chicago, IL; Department of Medicine, The University of Chicago, Chicago, IL; Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, IL.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Ratain
authors.affiliation: Center for Personalized Therapeutics, The University of Chicago, Chicago, IL; Department of Medicine, The University of Chicago, Chicago, IL; Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, IL. Electronic address: podonnel@medicine.bsd.uchicago.edu.
authors.forename: Peter H
authors.initials: PH
authors.lastname: O'Donnell
mesh_terms: D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D015510:Clinical Medicine; D004348:Drug Labeling; D005838:Genotype; D006801:Humans; D017063:Outcome Assessment, Health Care; D018579:Patient Selection; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D010818:Practice Patterns, Physicians'
chemical_list: D002317:Cardiovascular Agents