Clinically actionable genetic variation in patients with or at high-risk of cardiovascular diseases from the Montreal Heart Institute

Pharmacogenomics enables treatments to be tailored to individual genetic profiles, optimizing efficacy while reducing adverse effects. The Clinical Pharmacogenetics Implementation Consortium (CPIC) classifies gene-drug pairs by their level of evidence. Level A and B pairs are considered actionable, indicating that prescribers should (A) or could (B) modify therapy. This cross-sectional study aimed to assess the prevalence of actionable CPIC variants in the Montreal Heart Institute (MHI) Hospital Cohort. Genotyping was performed at the MHI Beaulieu-Saucier Pharmacogenomics Center using Agena’s MassARRAY and Illumina’s Global Screening Array. Genes ABCG2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A5, CYP4F2, DPYD, HLA-A, HLA-B, SLCO1B1, TPMT, UGT1A1, and VKORC1 were analyzed in 10,082 participants. Participants had an average of 3.9 genes with actionable variants, and among the full cohort, 99.7% carried at least one actionable variant. Of the 65 CPIC level A or B gene-drug pairs evaluated, 57 involved medications used by at least one participant. Nearly 40% of participants had at least one actionable gene-drug pair - that is, they were taking a medication for which they carried an actionable variant. This study confirms the high prevalence of actionable genetic variants in individuals with or at high risk of cardiovascular diseases.