Blood clotting, or coagulation, is an important process that prevents excessive bleeding when a blood vessel is injured.
The body has an extensive system to regulate clot formation; however, if a clot forms inappropriately it can become extremely dangerous by blocking the flow of blood. Deep-vein thrombosis (DVT) is an example of an abnormal blood clot that forms in a major vein of the leg. If these clots break off from the vein, they can travel to the lung and cause pulmonary embolism (PE). DVT and PE are known collectively as a venous thromboembolism (VTE).
VTE is a serious life-threatening condition that affects more that 1 million Americans annually. “VTEs are responsible for more deaths each year than motor vehicle accidents, HIV, and breast cancer combined,” says Roy Silverstein, MD, Chair, Department of Cell Biology, Cleveland Clinic.
VTEs are treated with anticoagulant therapy. “Thinning the blood” as a preventive measure against the formation of blood clots is not a novel idea. Hippocrates, “the Father of Medicine” even thought about it. However, it wasn’t until the 1954 introduction of the oral anticoagulant warfarin, a drug that inhibits the normal protective coagulation system that keeps patients from bleeding when a blood vessel is injured, that a new era in medical therapy was ushered in.
Unfortunately, problems with the drug’s unpredictable effects, the need for very close monitoring, long onset of action, and food and drug interactions that are among the most dangerous in clinical practice, have made warfarin therapy difficult to manage. Understandably, researchers have been looking for oral anticoagulant alternatives for years, especially for the treatment of VTE.
They may have finally found that alternative with two new non-vitamin K antagonist oral anticoagulants. Earlier this year, an advisory panel to the Food and Drug Administration voted to approve a novel once-daily oral anticoagulant that blocks Factor Xa, which is involved in clotting. The new pill prevents VTE in patients undergoing hip or knee replacement.
During total joint replacement procedures, the veins of the legs that carry blood back to the heart are damaged, which can significantly increase VTE risk for patients. More than half of patients not receiving preventive anticoagulant therapy develop life-threatening clots.
Already approved in Canada and Europe, the drug’s imminent approval in the United States will provide a more convenient way to allow patients to dose themselves rather than undergoing daily injections with drugs that are tricky to monitor.
The second blood-thinning drug is a novel medication called an oral direct thrombin inhibitor (DTI). The product of more than 20 years of research and development, this drug acts as an anticoagulant by directly inhibiting the enzyme, thrombin. The medication offers a predictable and well-tolerated oral therapy for patients at risk of thrombosis, one of the major causes of cardiovascular morbidity and mortality in the developed world. Phase III clinical trials are ongoing in the United States for the treatment and prevention of VTE in hip- and knee-replacement patients.
Study results with the drug are expected in 2009-2010, as are results of long-term therapy for stroke patients with atrial fibrillation. DTIs were recently approved for use in Europe and Canada.
Where Are They Now
Venous thromboembolism (VTE), which is caused by a blood clot, is a serious life threatening condition that affects more than 1 million Americans annually. Two newly developed non-vitamin K antagonist oral anticoagulants, which target the Factor Xa and thrombin respectively, now offer predictable and well-tolerated alternatives to the oral anticoagulant warfarin and can provide a more convenient-and safe-way for patients to dose themselves and prevent blood-clot formation.
There are now 4 factor Xa inhibiting drugs available on the market, with the most recent receiving approval in 2017, and NOACs now account for 60% of the market that previously belonged to warfarins. In 2015, the FDA will begin reviewing an antidote for one of the drugs, and if approved, this could bolster the sales even more. Non-vitamin K antagonist oral anticoagulants (NOACs) were studied in a 2016 published trial in Denmark, the conclusions drawn were that NOACs are safe and effective alternatives to warfarin. The one year follow ups concluded that NOACs are associated with lower rates of systemic embolism or ischemic stroke and as a result are effective alternatives in a clinical setting.