Current insights on cardiovascular and neurodegenerative relations of direct oral anticoagulants and their biotransformation

An intriguing connection explored over the years is the link between neurodegenerative diseases and thrombosis. A number of studies have focused on associations between cardiovascular events and neurodegenerative diseases such as Alzheimer’s, Parkinson’s, multiple sclerosis, and Huntington’s. This evolving concept has led to numerous investigations of the role of coagulation factors and innate immune components in the pathogenesis of neurological diseases. On the other hand, it is well known that for decades, vitamin K antagonists such as warfarin and acenocoumarol were the only oral anticoagulants available for treating and preventing deep vein thrombosis (DVT), pulmonary embolism (PE), and PE following hip or knee replacement surgeries. They were also used for stroke prevention and for reducing the risk of major cardiovascular events in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD). However, the need for frequent international normalized ratio (INR) monitoring, clinic visits, and dietary restrictions posed barriers to the optimal use of vitamin K antagonists in real-world practice. The advent of non–vitamin K antagonists, also known as direct oral anticoagulants (DOACs), has provided an important alternative, and they are now recommended as preferred over warfarin or acenocoumarol whenever possible, based on clinical trial findings and real-world evidence for more than 14 years. Thus, the objective of this review is to summarize the latest advancements in the therapeutic applications of DOACs and to present insights into their biotransformation and the impact of the CYP450 enzyme system on their metabolism.