Table 3:

Expert Guidelines Regarding Utilization of Genotype-Guided Drug/Dose Selection in Cardiovascular Disease

Class	Medication(s)	Gene(s)	Clinical Concern	Relevant Society/Regulatory Agency Recommendations	CPIC Strength	Ref.
Anti-platelet	Clopidogrel	CYP2C19	Clinical efficacy in ACS patients undergoing PCI	AHA/ACC recommendations: Due to lack of RCTs, the evidence base is insufficient to recommend routine CYP2C19 genotyping, but can be considered on a case-by-case basis for individuals at high-risk for poor outcomes.   CPIC Dosing Guidelines: Ultra-rapid - Standard dosing Extensive - Standard dosing. Intermediate - Alternative agent. Poor - Alternative agent.   FDA recommendations: Due to the estimated 2–14% of individuals who are poor metabolizers alternative dosing or anti-platelet agents should be considered. Clinical CYP2C19 genotyping is available to identify poor metabolizers	Moderate -to- strong	113, 141
β-blockers	Carvedilol Metoprolol Propranolol	ADRB1 CYP2D6 GRK4 GRK5	Therapeutic response	No recommendations have been made by CPIC, AHA/ACC, or regulatory agencies.	N/A	N/A
Statins	Simvastatin	SLCO1B1	Statin-induced myopathy	AHA/ACC recommendations: No formal recommendations.  yCPIC Dosing Guidelines: Normal function - Standard starting dose. Intermediate function - Consider alternative. Low function - Consider alternative; CK surveillance.   FDA recommendations: Simvastatin 80 mg should not be started in patients with a new clinical indication for a statin.	Strong	123
Vitamin K antagonist	Warfarin	CYP2C9 and VKORC1	Clinical efficacy and toxicity	AHA/ACC recommendations: No formal recommendations.   CPIC Dosing Guidelines: Recommend use of pharmacogenetic-guided warfarin dosing algorithms that account for CYP2C9 and VKORC1 genetic variation (e.g. http://www.warfarindosing.org).   FDA recommendations: Recommend use of electronic (e.g. http://www.warfarindosing.org) or table genetic-guided algorithms that account for CYP2C9 and VKORC1 genetic variation to establish initial dosing when possible.	Strong	142

^aACC = American College of Cardiology; ACS = acute coronary syndrome; AHA = American Heart Association; CK = creatinine kinase; CPIC = Clinical Pharmacogenomics Implementation Consortium; FDA = Food and Drug Administration; and PCI = percutaneous coronary intervention.