Anticoagulants are drugs that treat or prevent blood clots by acting on the body’s clotting system. It can be used to treat blood clots in the legs (called deep vein thrombosis or DVT), blood clots in the lungs (pulmonary embolism or PE), other arterial and venous thrombosis, heart rhythm disorders (atrial fibrillation or AF) when there is an increased risk of stroke, and mechanical heart valves. For decades, warfarin has been the most commonly used anticoagulant. In recent years, several new oral anticoagulants (NOACs) have been marketed as alternatives to warfarin. Therefore, patients who need anticoagulation now have options, and the benefits, risks, side effects and convenience should be considered when choosing. Xiaoli Liu, Department of Major Internal Medicine, Shanghai Deji Hospital What is the difference between the new oral anticoagulants and warfarin? Warfarin treatment and prevention of thrombosis works by decreasing the synthesis of vitamin K-dependent coagulation factors. Warfarin is administered orally once daily, and the dose taken varies with genetic factors, the reason for the medication, and dietary factors. Because the dose varies from patient to patient, frequent monitoring of blood indicators and adjustment of the dose is required to achieve the appropriate level (this indicator is called the International Normalized Ratio or INR). If the target level is not reached, the patient is at increased risk of blood clots; while above the target level, the risk of bleeding increases. All anticoagulants increase the risk of bleeding, and when warfarin causes an increased risk of bleeding, vitamin K or blood products can be applied to supplement clotting factors. Newer oral anticoagulants work by acting on different clotting proteins. They have predictable effects when applied, so there is no need to monitor blood markers or to adjust the dose. They have a shorter duration of action than warfarin. The effect of warfarin can last for several days and the anticoagulant effect is not significantly affected if a single dose of warfarin is missed. In contrast, if a new oral anticoagulant is missed once, the anticoagulant effect decreases rapidly. If a patient bleeds, warfarin has an antidote, whereas the newer oral anticoagulants do not have a specific antidote (their antidote is currently in clinical trials and not yet available). Patients on warfarin who require surgery or invasive procedures will need to discontinue warfarin for several days, and may need to apply short-acting injectable anticoagulants or inpatient intravenous anticoagulants to prevent blood clots (called bridging) while they are discontinued. Newer oral anticoagulants rarely require bridging because of their short duration of action, and can be discontinued for one to two days before surgery. Newer oral anticoagulants are taken once or twice daily (varies by drug and by disease). Newer oral anticoagulants have a proven role in stroke prevention in atrial fibrillation and in the treatment and prevention of deep vein thrombosis and pulmonary embolism, but should not be used in patients with mechanical heart valves. Warfarin Warfarin has been used for decades in the treatment of patients with atrial fibrillation, deep vein thrombosis, pulmonary embolism, and mechanical heart valves. Its most commonly used target INR level is 2 to 3. It is inexpensive. There are some problems with warfarin application. First, it requires several days of dosing before it may reach the target. Therefore, anticoagulant injections are often required before it can take effect. The INR often fluctuates, requiring dose adjustments and frequent monitoring of blood indicators. Sometimes, brain bleeding can occur even when the INR is not exceeded. Foods high in vitamin K (dark leafy greens, such as spinach) can lower the INR, and some medications (including some antibiotics) can raise the INR. hundreds of drugs can interact with warfarin, so patients must tell their doctors about medication changes. Dabigatran For patients with atrial fibrillation, dabigatran is better than warfarin at preventing stroke and reducing the risk of brain hemorrhage. For the treatment of deep vein thrombosis and pulmonary embolism, dabigatran and warfarin are similarly effective. The dose of dabigatran is 150 mg twice daily. In renal insufficiency, the dose may need to be reduced to 75 mg twice daily. Rivaroxaban For stroke prevention in atrial fibrillation, rivaroxaban and warfarin are similarly effective, with a reduced risk of cerebral hemorrhage. For the treatment and prevention of deep vein thrombosis and pulmonary embolism, rivaroxaban and warfarin are comparable in effectiveness, with a low risk of serious bleeding complications. Dosing is by oral administration once to twice daily. Dosage may need to be reduced in patients with chronic kidney disease. Apixaban For stroke prevention in atrial fibrillation, apixaban is preferred to warfarin twice daily. For the treatment and long-term prevention of deep vein thrombosis and pulmonary embolism, the two are equivalent. Apixaban has fewer serious bleeding complications than warfarin. Apixaban has the lowest renal clearance of all the new oral anticoagulants and is mostly metabolized by the liver. Edoxaban (edoxaban) Edoxaban has similar effects to warfarin once daily for stroke prevention in atrial fibrillation and for the treatment of deep vein thrombosis and pulmonary embolism, and has fewer serious bleeding complications than warfarin. New oral anticoagulants and mechanical heart valves Mechanical valves are at increased risk of thrombosis and anticoagulants (commonly warfarin) must be used to prevent thrombus formation on the valve. Newer oral anticoagulants have been poorly studied for this indication, and one study showed that dabigatran is less effective than warfarin for mechanical valves and bleeding is more common. How to choose? There are now many options for the treatment and long-term prevention of deep vein thrombosis and pulmonary embolism, as well as stroke prevention in atrial fibrillation. For some patients, they may prefer the similar or even better results and better safety profile of newer oral anticoagulants. Other patients may prefer the classic drug (warfarin). European medical societies’ guidelines recommend that the best choice for stroke prevention in atrial fibrillation is a new oral anticoagulant. US guidelines recommend newer oral anticoagulants for patients who have difficulty maintaining an INR at target levels. Warfarin has a specific antidote, whereas specific antidotes for newer oral anticoagulants are not yet available. Medication adherence is also important. Patients who sometimes forget to take their medication may be better off with warfarin, which has a longer duration of action and INR monitoring to remind patients. In terms of convenience, the new oral anticoagulants do not require monitoring of blood markers, do not require dose adjustment, and have essentially no interaction with food and other medications. In addition, there are cost issues to consider.