Drug–Drug–Gene Interactions in Cardiovascular Medicine

Abstract

Cardiovascular disease remains a leading cause of both morbidity and mortality worldwide. It is widely accepted that both concomitant medications (drug–drug interactions, DDIs) and genomic factors (drug–gene interactions, DGIs) can influence cardiovascular drug-related efficacy and safety outcomes. Although thousands of DDI and DGI (aka pharmacogenomic) studies have been published to date, the literature on drug–drug–gene interactions (DDGIs, cumulative effects of DDIs and DGIs) remains scarce. Moreover, multimorbidity is common in cardiovascular disease patients and is often associated with polypharmacy, which increases the likelihood of clinically relevant drug-related interactions. These, in turn, can lead to reduced drug efficacy, medication-related harm (adverse drug reactions, longer hospitalizations, mortality) and increased healthcare costs. To examine the extent to which DDGIs and other interactions influence efficacy and safety outcomes in the field of cardiovascular medicine, we review current evidence in the field. We describe the different categories of DDIs and DGIs before illustrating how these two interact to produce DDGIs and other complex interactions. We provide examples of studies that have reported the prevalence of clinically relevant interactions and the most implicated cardiovascular medicines before outlining the challenges associated with dealing with these interactions in clinical practice. Finally, we provide recommendations on how to manage the challenges including but not limited to expanding the scope of drug information compendia, interaction databases and clinical implementation guidelines (to include clinically relevant DDGIs and other complex interactions) and work towards their harmonization; better use of electronic decision support tools; using big data and novel computational techniques; using clinically relevant endpoints, preemptive genotyping; ensuring ethnic diversity; and upskilling of clinicians in pharmacogenomics and personalized medicine.

Landscape of pharmacogenetic variants associated with non-insulin antidiabetic drugs in the Indian population

“…The CYP inhibitor data were obtained by overlapping 44 NIADs and 242 metabolic disease drugs with the Flockhart table of drug–gene interactions. Known DDGIs were primarily compiled from recent review studies 14 29 30…”

Genotyping of Patients with Adverse Drug Reaction or Therapy Failure: Database Analysis of a Pharmacogenetics Case Series Study

“…After consideration of these aspects, the results of the database analysis, and indications of research, [37][38][39][40][41][42][43][44] we consider the following target groups of our patient sample to be suitable for benefiting from pharmacogenotyping: Patients taking drugs for mental or behavioral disorder, circulatory diseases, selected immunological diseases (eg, rheumatic diseases, chronic inflammatory bowel diseases (IBD)), pain patients taking analgesics or opioids on a regular basis and patients experiencing polypharmacy, especially the elderly. However, before genotyping the afore-identified target groups, we suggest to check first if their suspected substances are associated with PGx in literature at all.…”

Pharmacogenomics of Cardiovascular Drugs for Atherothrombotic, Thromboembolic and Atherosclerotic Risk

“…Pharmacogenomics is the science of understanding how genetic variability influences drug treatment outcomes. The prevalence of cardiovascular diseases is increasing over time, and heart diseases represent the leading cause of mortality globally [1]. Patients with cardiovascular diseases frequently show multimorbidity, defined as the presence of at least two pathologies, and are in need of multiple medication regimens, often resulting in polypharmacy, which is defined as five or more daily medications.…”

“…Patients with cardiovascular diseases frequently show multimorbidity, defined as the presence of at least two pathologies, and are in need of multiple medication regimens, often resulting in polypharmacy, which is defined as five or more daily medications. This condition results in an increased risk of drug-drug interactions (DDIs), drug-gene interactions (DGIs) and drug-drug-gene interactions (DDGIs) [1]. Cardiovascular drugs, in particular antiplatelets and anticoagulants, are the main causes of DDIs, DGIs, and DDGIs.…”

“…Cardiovascular drugs, in particular antiplatelets and anticoagulants, are the main causes of DDIs, DGIs, and DDGIs. Several studies [1][2][3][4][5] and guidelines [6][7][8] focus on DGIs; however, data on DDGIs remain limited.…”