Introduction: The safety and efficacy of cardiovascular drugs can be affected by interactions involving other drugs or genetic factors, including multifactorial drug-gene interactions. Such interactions are important considerations for optimal treatment.1
Objectives: To investigate prevalence of drug-drug interactions, drug-gene interactions and multifactorial drug-gene interactions among older Australians taking the cardiovascular drugs clopidogrel, warfarin and statins.
Methods: Co-prescription prevalence was obtained from self-reported medication data from the Hunter Community Study (HCS), an Australian population based cohort of individuals aged 55-85 years.2 Interacting drugs were identified from U.S. Food and Drug Administration (FDA), Monthly Index of Medical Specialties (MIMS), Australian Medicines Handbook (AMH) and other resource.3-6 Participants were genotyped using Affymetrix Kaiser Axiom arrays or imputation from HapMap 2 and 1000 Genome reference panels.
Results: Of 92 participants on clopidogrel, potential drug-drug interactions were identified in 84 participants (91.3%, 95% CI; 86%-97%) with 1.9 interactions on average per participant (1.9±0.9; 95% CI; 1.7-2.1). Of 116 participants on warfarin, potential drug-drug interactions were identified in 93 participants (80.2%, 95% CI; 73%-87%) with 3.0 interactions on average per participant (3.0±2.4; 95% CI; 2.6-3.5). Of 976 participants on statins, potential drug-drug interactions were identified in 303 participants (31.1%; 95% CI; 28%-34%) with 1.8 interactions on average per participant (1.8±1.2; 95% CI; 1.7-1.8). In total, 8.9% (95% CI; 7%-11%) of all participants co-prescribed interacting drugs were determined to be at risk of five or more interactions. Clinically actionable drug-gene interactions were found for 26% of participants taking cardiovascular drugs and for whom genotype data were available (95% CI; 21%-31%). Clinically actionable multifactorial drug-gene interactions were found in 14% of these participants (95% CI; 7%-21%) taking interacting drugs.
Conclusions: The findings suggest some proportion of older Australians are at serious risk of adverse cardiovascular events, providing evidence that analysing genetic status and drug-drug interactions may improve medication safety and effectiveness.