The new anticoagulants rivaroxaban, apixaban, and dabigatran promise several benefits, but are not suitable for all patient populations. Various questions arise in primary care practice, which were discussed at this year’s Medidays in Zurich. First, it should be decided for which patients a new setting or a switch to these substances is appropriate.
Jan-Dirk Studt, MD, from the Clinic for Hematology at the University Hospital Zurich, spoke about common problems encountered by family physicians. First, he briefly introduced the new anticoagulants available in Switzerland, the oral direct thrombin inhibitor dabigatran and the two oral direct factor Xa inhibitors rivaroxaban and apixaban.
“Dabigatran is approved in Switzerland for embolic prophylaxis in atrial fibrillation (AF) in both doses of 110 and 150 mg (2×/day each). Rivaroxaban is approved for the prophylaxis of venous thromboembolism (VTE) during major orthopedic lower extremity surgery (1×10 mg/day), for acute therapy and secondary prophylaxis of VTE (first three weeks 2×15, then 1× 20 mg/day), and for embolic prophylaxis in VCF (1×20 or 1×15 mg/day). The current approval of apixaban in Switzerland covers thromboembolism prophylaxis after total hip and total knee replacement surgery (2×2.5 mg/day),” Dr. Studt said.
These are the hard facts, but a variety of questions and unresolved issues arise from practice:
- Who should be switched to the new anticoagulants?
- What is the response for bleeding, overdose, and intervention?
- How should special patient groups be handled (tumor patients, mechanical heart valves, pregnancy, patients with renal insufficiencies)?
- Monitoring: When, Who and How?
Who should you change over?
There is currently no reason for a general switch of patients who have been treated with VKA without any problems to the new anticoagulants. However, this may be appropriate for certain patient populations, e.g.:
- Practical difficulties with Quick/INR measurement (e.g., poor accessibility of measurement site, frequent travel).
- Unstable INR setting despite good compliance or very high VKA dose requirement (“Marcoumar resistance”).
- Adverse side effects of VKA (e.g., hepatitis).
- Adverse drug interactions with VKA
- Frequent interventions with need for VKA bridging.
- Hemostaseologic special cases (e.g., preexisting factor VII deficiency, factor IX propeptide mutation).
- Because of the somewhat lower rate of intracranial hemorrhages, at least according to studies to date, the new anticoagulants could be an interesting option, especially for patients with VCF.
How to behave in case of interventions and bleeding?
Regarding interventions, for example, the following can be said for rivaroxaban:
- Dose 10 mg -> Stop at least 18 (24) hrs prior to intervention or catheter placement or removal.
- Dose 15 or 20 mg -> at least 24 hrs prior to intervention.
- Next dose from about 6-8 hrs after intervention.
These times can be considerably longer in the case of renal insufficiency. Dabigatran should be discontinued at least 24 h prior to interventions, 36-48 h prior for high-risk interventions (e.g., CNS), possibly longer if renal function is impaired.
“What should you do if you’re bleeding?” posed the question to Dr. Studt. “It should be noted up front that no specific antidote is currently available for any of the new anticoagulants. A pragmatic approach must therefore be taken.
In the case of minor bleeding, a symptomatic approach is recommended (local measures, use of tranexamic acid if necessary, postponement of the next dose if necessary). In general, however, medication does not yet have to be stopped completely.
On the other hand, in the case of more severe bleeding, interruption is advisable, as well as hospitalization. To optimize hemostasis, prothrombin complex concentrate is usually administered, sometimes also recombinant activated factor VII. In addition, for dabigatran, which is renally eliminated, dialysis may be attempted in the first few hours.”
Special patient groups
Several limitations should be noted:
- Patients with renal insufficiency: do not use the new anticoagulants if creatinine clearance <30 ml/min, careful risk-benefit evaluation and monitoring if necessary <30 ml/min. In the range between 30-50 ml/min. Careful risk-benefit evaluation, if necessary consideration of a dose reduction depending on the indication and preparation, and monitoring if necessary. Regular monitoring of kidney function is recommended, e.g. before starting medication and every six months. Besides, in advanced hepatopathy, no use of rivaroxaban.
- According to current studies, the new anticoagulants cannot be used in patients with mechanical prosthetic heart valves (contraindication for dabigatran, insufficient study data for the others).
- No use of the new anticoagulants in pregnant and breastfeeding women
- No sufficient data basis for the use of the new anticoagulants for prophylaxis or therapy of tumor-associated thromboembolism
- No approval of the new anticoagulants for thromboembolism prophylaxis in medical patients or for prophylaxis of so-called travel thrombosis.
Forgetting to take a dose
Using the example of rivaroxaban, Dr. Studt explained the correct behavior if the patient forgets to take the drug:
If taken once daily: the dose should be retaken as soon as the error is noticed, the daily dose should not be exceeded.
If taken twice daily (initial phase of acute therapy of venous thromboembolism): Immediately take the missed dose, continue the next day at the usual time.
Source: “The change in anticoagulation from three perspectives: guidelines, patient, GP”, satellite symposium of Bayer (Schweiz) AG & baumann medical ag at Medidays, September 2-6, 2013, Zurich.
HAUSARZT PRAXIS 2013; 8(11): 37-38
CONGRESS SPECIAL 2014, 6(1): 24-25
