Mayo Clin Proc. 2015 Jun;90(6):716-29. doi: 10.1016/j.mayocp.2015.03.016.

Evidence for Clinical Implementation of Pharmacogenomics in Cardiac Drugs.

Kaufman AL¹, Spitz J², Jacobs M², Sorrentino M³, Yuen S², Danahey K⁴, Saner D⁴, Klein TE⁵, Altman RB⁶, Ratain MJ⁷, O'Donnell PH⁸.

Author information

1: Pritzker School of Medicine, The University of Chicago, Chicago, IL.
2: Center for Personalized Therapeutics, The University of Chicago, Chicago, IL.
3: Department of Medicine, The University of Chicago, Chicago, IL.
4: Center for Research Informatics, The University of Chicago, Chicago, IL.
5: Department of Genetics, Stanford University, Palo Alto, CA.
6: Department of Genetics, Stanford University, Palo Alto, CA; Department of Bioengineering, Stanford University, Palo Alto, CA; Department of Medicine, Stanford University, Palo Alto, CA.
7: 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.
8: 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.

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.

CONCLUSION:

Considerable clinically actionable pharmacogenomic information for cardiovascular drugs exists, supporting the idea that consideration of such information when prescribing is warranted.