Cardiology Internal Medicine

Anticoagulants

Anticoagulants

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

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:

Dabigatran
(Pradaxa)
Rivaroxaban
(Xarelto) 
Apixaban
(Eliquis)
Edoxaban (Lixiana)Warfarin
(Waran)
ProdrugYesNoNoNoNo
Factor Xa inhibitorNoYesYesYesNo
Thrombin inhibitorYesNoNoNoNo
Bioavailability (%)6> 80> 5045100
Time to peak (h)2331.5120
T½ (h)12-1799-149-1150
InteractionsP-glyco-proteinCYP3A4
β-glyco protein
CYP3A4
β-glyco protein
CYP3A4
β-glyco protein
Long list
Renal excretion (%)803325501
AntidoteYesNo*No*No*Yes

* 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.


Indications

Warfarin is used today for a variety of indications, some of which are listed below.

DabigatranRivaroxabanApixabanEdoxabanWarfarin
Prophylaxis in elective hip or knee surgeryYesYesYesYesYes
Prophylaxis in surgery, trauma or other patients with increased thrombosis riskNoNoNoNoYes
Stroke prevention in nonvalvular atrial fibrillationYesYesYesYesYes
Secondary prophylaxis deep vein thrombosis (DVT) or pulmonary embolismYesYesYesYesYes
Acute coronary syndromeNoYesNoNoYes
Mechanical valve prosthesisNoNoNoNoYes

Treatment – Anticoagulants

Practical advice on medication initiation

In general, one should be cautious in renal failure patients.

Testing

  • CBC
  • Creatinine
  • 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.

Patient information

Both written and verbal information to patients should be given. This should include: 

  • Purpose of treatment
  • Risks/benefits
  • Bleeding/thrombosis
  • Interventions in bleeding events
  • Side effects
  • Painkillers
  • Diet
  • Alcohol
  • Operations
  • Interventions
  • Follow-up
  • Renal function
  • Fertile women
  • Pregnancy
  • 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.


Side effects

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.

Further Reading