Introduction – Anticoagulants
This is an overview of oral anticoagulants, such as warfarin and factor Xa and thrombin inhibitors, including the indications for such treatments.
Warfarin (Waran/Warfarin) has been used since the 1950s. In recent years, the prescription has gradually decreased, mainly because more and more patients with atrial fibrillation are now being introduced to new oral anticoagulants (NOAC) instead.
There are some well-known problems with warfarin treatment, of which the risk of significant bleeding is the most central. The treatment requires monitoring of the anticoagulation level by measuring the INR and individual dosing. The list of possible interactions with food and drugs is long.
New oral anticoagulants
Several new oral anticoagulants are available. Internationally, the abbreviation NOAC (New Oral Anticoagulants) is often used.
Common benefits are:
- They do not need to be monitored with INR measurements
- Rapid onset of action (1.5-3 hours)
- Lower risk of cerebral hemorrhage than warfarin
Overview – Anticoagulants
Overview of oral anticoagulants:
|Factor Xa inhibitor||No||Yes||Yes||Yes||No|
|Bioavailability (%)||6||> 80||> 50||45||100|
|Time to peak (h)||2||3||3||1.5||120|
|Renal excretion (%)||80||33||25||50||1|
* Andexanet alfa (Ondexxya) is available as an antidote to factor Xa inhibitors. Due to short (two hours), incomplete effect and high price, today it is recommended to use prothrombin concentrate (Confidex or Ocplex), instead, in clinical practice in severe bleeding or in need of urgent surgery.
Of the new oral anticoagulants, there is a thrombin inhibitor, dabigatran (Pradaxa) and three factor Xa inhibitors – rivaroxaban (Xarelto), apixaban (Eliquis) and edoxaban (Lixiana). Dabigatran is distinguished by having lower bioavailability and a higher proportion of renal excretion.
Warfarin is used today for a variety of indications, some of which are listed below.
|Prophylaxis in elective hip or knee surgery||Yes||Yes||Yes||Yes||Yes|
|Prophylaxis in surgery, trauma or other patients with increased thrombosis risk||No||No||No||No||Yes|
|Stroke prevention in nonvalvular atrial fibrillation||Yes||Yes||Yes||Yes||Yes|
|Secondary prophylaxis deep vein thrombosis (DVT) or pulmonary embolism||Yes||Yes||Yes||Yes||Yes|
|Acute coronary syndrome||No||Yes||No||No||Yes|
|Mechanical valve prosthesis||No||No||No||No||Yes|
Treatment – Anticoagulants
Practical advice on medication initiation
In general, one should be cautious in renal failure patients.
- INR, APTT
- Liver panel
Creatinine is used to calculate eGFR.
INR, APTT are important reference tests as they can later be used to estimate the anticoagulation effect in the event of any bleeding complication or need for surgery. Note that Apixaban (Eliquis) has no effect on APTT or INR even at high concentrations, so these tests cannot be used to estimate the anticoagulant effect of these drugs.
Both written and verbal information to patients should be given. This should include:
- Purpose of treatment
- Interventions in bleeding events
- Side effects
- Renal function
- Fertile women
- Missed dose risks
The patient information can be provided by a trained nurse at the anticoagulation clinic.
Patients started on NOAC should be followed up with computerized prescription support.
In addition to bleeding, the side effects are few. Dabigatran increases the risk of dyspepsia which is believed to be due to the capsules containing tartaric acid to improve the uptake of the drug.
Switch between different anticoagulants
- Switch from warfarin to new oral anticoagulant (NOAC) – quit warfarin and start NOAC when INR is <2.0.
- Change from heparin/low molecular weight heparin (LMWH) to NOAC – give first dose of NOAC 0-2 hours before the next dose of LMWH was planned or 0-2 hours after heparin infusion is stopped.
- Change from new oral anticoagulant to warfarin – please see below. The timing of initiation of warfarin depends on the patient’s estimated residual effect of the previous preparation, depending on the renal excretion of the preparation in question and the patient’s renal function estimated with eGFR.
- Change from new oral anticoagulant to heparin/LMWH – give heparin / LMWH at the time of the next scheduled dose io non-renal failure patients.
- Switch between two new oral anticoagulants – if no renal failure, the new preparation can be given at the time of the next scheduled dose.
When switching from NOAC to warfarin
- eGFR >50 ml/min:
Start warfarin treatment as usual 2-3 days before discontinuing NOAC therapy.
- eGFR 31-50 ml/min:
Start warfarin treatment 1 day before discontinuing NOAC therapy.
- eGFR 15-30 ml/min:
Start warfarin treatment 1 day after NOAC treatment ends.
- eGFR <15 ml/min:
NOAC is contraindicated, there is a high risk of bleeding. Contact coagulation experts.
- Weitz JI, Eikelboom JW, Samama MM. New Antithrombotic Drugs. Antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. CHEST 2012;141(2)(Suppl):e120S-e151S.
- ESC guidelines, EHRA practical guide NOAC.
- An updated meta-analysis of novel oral anticoagulants versus vitamin K antagonists for uninterrupted anticoagulation in atrial fibrillation catheter ablation.
- Novel Oral Anticoagulants in Peripheral Artery Disease: Current Evidence.
- Novel Oral Anticoagulation Laboratory Monitoring, Interaction and Treatment of Complications.
- Gastrointestinal bleeding in patients on novel oral anticoagulants: Risk, prevention and management.