Pharmacology of Anticoagulants, Antithrombotics, and Antiplatelet Drugs

AnticoagulantAnticoagulant therapiesAgents and therapies, which include antiplateletAntiplatelet and antithromboticAntithrombotic drugs, prevent and treat many cardiovascular disorders and are some of the most universally prescribed drugs. Rapid onset anticoagulant therapy is also required to perform a number of clinical procedures including percutaneous coronary interventions (PCI), structural heart interventions, cardiovascular surgery, and other surgeries, as well as dialysis. This therapy is also used as a treatment for a number of thrombotic diseases including acute coronary syndromes (myocardial infarction and unstable angina), deep vein thrombosis, and pulmonary embolism. The hematologic system involves a complex interaction of the vascular endothelium, plateletsPlatelets, and coagulationCoagulation factors. As long as the fine-tuned interplay within the system is balanced, neither thrombus formation or bleeding and any associated consequences will take place. Perioperatively, hemostasis is often challenged but perturbations of the integrity of the vascular endothelium and subsequent platelet activation may result in acute clot formation in the arteries or veins, which ultimately manifests as arterial or venous thromboembolism. This is where anticoagulant drugs including antiplateletAntiplatelet therapies and antithromboticAntithrombotic agents are utilized to interfere with hemostasis. When selecting the most appropriate anticoagulant drug, thorough consideration of the efficacyEfficacy to safetySafety ratio is warranted. In addition, there are a number of pharmacological factors that affect a drug’s success: the absorption rate, the overall metabolismMetabolism, an active parent drug rather than a prodrug that needs to be metabolized, drug interactionsDrug interactions, interpatient variability in anticoagulant effects (e.g., drug, environment, and genetic), onset of action, pharmacokineticsPharmacokinetics with a dose-dependent drug effect, elimination, and a direct target. The overarching goal over the last several years has been to develop antithrombotic, anticoagulant, and antiplatelet drugs that carry more favorable pharmacological properties (e.g., faster onset of action, fewer interactions, and less interpatient variability in their antithrombotic effects) thus reducing thrombotic events without generation of unacceptably high bleeding rates. Besides more original drugs such as unfractionated heparin (UFH), the antiplateletAntiplatelet agents aspirinAspirin and clopidogrel and the vitamin K antagonist warfarin, modern treatment options now include anticoagulants that directly target factor IIa (bivalirudin, argatroban, dabigatran) or Xa (rivaroxaban, apixaban, edoxaban) and the next-generation antiplatelet drugs prasugrel and ticagrelor. This chapter focuses on the pharmacological properties, monitoring, and strategies for reversal of the most commonly used anticoagulantsAnticoagulant, antithrombotics,Antithrombotic and antiplatelet drugs.