Antithrombotic agents and drug–drug interactions

Abstract Drug–drug interactions affecting antiplatelet and anticoagulant medications are not uncommon, and among patients with cardiovascular disease, many receive polypharmacy thereby increasing the risk for important drug interactions. Such interactions may impact the efficacy or safety, or both, of antithrombotic medications. Since vitamin K antagonists have been widely used in clinical medicine for many years, drug interactions with agents such as warfarin are well known. Over recent years, newer and more potent antiplatelet and anticoagulant agents have been developed, and each of these has an identified potential to be impacted by other medications, primarily by affecting hepatic cytochromes involved with drug metabolism. While many interactions have been identified and alterations of plasma concentrations of drugs have been found, limited meaningful impacts on clinical outcomes have been discerned from large-scale trials. Drugs which importantly alter renal function may also pose a drug clearance issue for agents with a high proportion of the active compound being renally excreted. Lastly, the combination of anticoagulant agents poses the highest risk to patients as the antithrombotic impact is greatest as well as the risk for drug-related interactions among the antithrombotic agents and with other drugs. Recognition of these risks has led to increased scrutiny of anticoagulant safety by clinical care providers, pharmaceutical companies, health agencies, as well as accrediting bodies.