Novel oral anticoagulants (NOACs), or oral direct anticoagulants (DOACs), are now increasingly used clinically in the prevention and treatment of venous thromboembolism (deep vein thrombosis, pulmonary embolism) and in stroke prevention in atrial fibrillation. Currently, dabigatran and rivaroxaban are available in China. The advantages of the new oral anticoagulants over warfarin are the application of a fixed dose (1 to 2 times daily), no need to monitor coagulation, few drug interactions, and no influence by food.
General questions.
Q: Can new oral anticoagulants be taken with food?
A: Dabigatran capsules should be taken with a meal and should not break the capsule. Rivaroxaban should be taken with a meal to increase absorption and the tablets can be crushed and taken with soft foods. Apixaban may or may not be taken with or without a meal.
Q: Are there any foods or beverages that I should not eat while taking the new oral anticoagulants?
A: Unlike warfarin, there are no food contraindications to taking the newer anticoagulants. Grapefruit juice can affect the metabolism of many drugs, but it also has no significant effect on the newer oral anticoagulants. In general, small amounts of alcohol (e.g., a glass of red wine) are allowed when taking novel oral anticoagulants.
Q: What should I do if I experience stomach upset when starting a new oral anticoagulant?
A: Stomach upset occurs in about 10% of patients when starting dabigatran and is relatively uncommon with rivaroxaban. Taking the drug with a meal may reduce the chance of stomach upset, and it often resolves on its own after a few days. Antacids may have a role, but studies are lacking.
Q: Can I take the new oral anticoagulants in my own small pillbox?
A: Rivaroxaban and Apixaban can be placed in a small pill box for a week or a month’s supply. Dabigatran should be kept in its original packaging until it is taken. Do not open the blister pack if it is in a pill box.
Q: What if I forget to take the medication at one time?
A: If you forget to take your medication one day, you should not double your dose the next day. For patients with atrial fibrillation, if you forget to take your medication once, just continue to take your regular dose the next time. However, if rivaroxaban is taken twice daily for three weeks prior to a venous thromboembolism, the missed dose should be made up as soon as possible to ensure that the two 15 mg doses of rivaroxaban were taken that day.
Q: What if a patient requires dental management?
A: For general dental management (e.g., scaling or extraction), the new oral anticoagulant may not need to be discontinued; tranexamic acid may be applied as a mouth rinse before and after the general procedure. Alternatively, the new oral anticoagulant may be discontinued the day before the operation and resumed the night after the operation. For other post-operative procedures, the guidance of a medical professional is required.
Q: What are the results for patients with prosthetic heart valves?
A: Novel oral anticoagulants are not used to treat patients with mechanical heart valves. In patients with bioprosthetic valves combined with atrial fibrillation or venous thromboembolism, novel oral anticoagulants can be applied.
Combination of novel oral anticoagulants with other medications.
Q: Can analgesics be combined with novel oral anticoagulants?
A: A class of pain relievers commonly used in clinical practice is called non-steroidal anti-inflammatory drugs (NSAIDs), which should be avoided in combination with new oral anticoagulants for a long time. However, for acute joint pain and other conditions, short-term (e.g. 3-5 days) combination applications are allowed. For arthralgia, headache, cold, flu, etc., the application of acetaminophen is safer than NSAIDs. If long-term co-administration is indeed required, special consultation with a medical professional should be sought.
Q: Are there other medications to avoid combining when taking new oral anticoagulants?
A: For dabigatran, amiodarone and azole antifungals increase blood levels and rifampin decreases blood levels. For rivaroxaban, azole antifungals and clarithromycin increase blood levels, and antiepileptics (e.g., phenytoin, carbamazepine) and rifampin decrease blood levels. For Apixaban, it may be similar to Rivaroxaban.
Q: Do herbs or supplements have any effect on the new oral anticoagulants?
A: Avoid St. John’s wort; no effect of other herbs has been found.
Patient monitoring and follow-up.
Q: Do patients taking the new oral anticoagulants require regular clinical follow-up?
A: Yes. Patients on long-term therapy should be followed up at least once every 6 to 12 months. They need to be evaluated for the presence of bleeding complications, to assess the risk of thromboembolism, to assess the risk of bleeding complications, and to assess renal function. These factors determine whether the dose of the new oral anticoagulant needs to be adjusted and whether it needs to be adjusted from one new oral anticoagulant to another or to warfarin. In addition, follow-up visits can assess patient compliance with medications, evaluate combined medications, and whether to temporarily interrupt therapy if manipulation is required.
Q: Do patients need routine coagulation tests?
A: No.
Q: Does the patient need to have any blood indicators routinely checked?
A: Yes. Renal function should be checked every 6 to 12 months, and changes in renal function determine the dose of medication or whether the medication needs to be switched.
Q: How do I switch to a new oral anticoagulant when I was taking warfarin?
A: After stopping warfarin, wait for the INR to drop to 2.0 or below before starting a new oral anticoagulant.
Some urgent questions for patients taking new oral anticoagulants.
Q: What happens when a patient has an acute ischemic stroke?
A: Management is similar to that of other patients with ischemic stroke. Thrombolysis should be considered in appropriate patients (especially if 12 to 18 hours have passed since the last dose of the new oral anticoagulant). Consider co-administration of antiplatelet agents. Interspecialist consultation should be considered in this situation.
Q: What happens when a patient has an acute coronary syndrome?
A: Management is similar to other patients with acute coronary syndromes. Interspecialist consultation is recommended.
Q: What happens when a patient has severe trauma or severe bleeding?
A: The focus is on supportive care and management of the cause of the bleeding. Interspecialist consultation is recommended.
Comparison of new oral anticoagulants.
Q: Are there any studies comparing various new oral anticoagulants?
A: There are no directly comparable randomized clinical trials. All of the current studies compare various new oral anticoagulants to traditional anticoagulants such as warfarin.
Q: Which of the newer oral anticoagulants are the most effective and safest for patients with atrial fibrillation?
A: Each has advantages and disadvantages. The choice is considered based on thrombotic risk, bleeding risk, comorbidities (history of stroke, renal insufficiency, etc.).
Consideration may be based on the following characteristics.
For AF patients at high risk of stroke (CHADS2 score of at least 3) or with a history of stroke, dabigatran 150 mg twice daily, rivaroxaban 20 mg once daily, and apixaban 5 mg twice daily can be applied.
For patients with atrial fibrillation at high risk of bleeding, apixaban 5 mg twice daily and dabigatran 110 mg twice daily may be applied.
In elderly patients (80 years or older) with decompensated renal function (CrCl <50 mL/min), apixaban 2.5 mg twice daily and rivaroxaban 15 mg once daily may be administered.
It is important to note that the above regimen is not limited to the above, and the advice of a medical professional should be followed for each case.
Q: Which new oral anticoagulant is the most effective and safest for patients with venous thromboembolism?
A: There are no directly comparable clinical trials.
Q: How do I use the medication in patients with decompensated renal function?
A: Dabigatran.
For CrCl >50 mL/min, apply 150 mg or 110 mg twice daily and recheck CrCl every 12 months.
For CrCl 30-50 mL/min, apply 110 mg or 150 mg twice daily and review CrCl every 6 months, also review CrCl in case of acute illness.
When CrCl <30 mL/min, try not to use it.
Rivaroxaban.
For CrCl >=50 mL/min, 20 mg once daily and review CrCl every 12 months.
For CrCl 30-49 mL/min, 15 mg once daily and review CrCl every 6 months, also in case of acute disease.
When CrCl < 30 mL/min, try not to use it.
Apixaban.
For CrCl >50 mL/min, 5 mg twice daily and review CrCl every 12 months.
CrCl 25-50 mL/min, 5 mg twice daily, reduced to 2.5 mg twice daily if both of the following apply: 1) creatinine >= 133 umol/L; 2) age >= 80 years; 3) weight <= 60 kg. review CrCl every 6 months, also in case of acute disease.
At CrCl 15-24 mL/min, clinical information is lacking.
When CrCl <15, try not to use it.