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Direct oral anticoagulants: Difference between revisions
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<section begin="clinical biochemistry" />'''Direct oral anticoagulants''' (DOACs) are commonly used [[anticoagulants]]. As the name suggests, they act directly on one of the [[clotting factors]] and because they’re taken orally (except argatroban).<section end="clinical biochemistry" /> | |||
DOACs are mostly used as safer and non-inferior alternatives to [[warfarin]]. | |||
They are also called '''novel oral anticoagulants''' (NOACs), although they were introduced in 2008, so this name is no longer fitting. | |||
== Compounds == | |||
* Direct thrombin inhibitors | |||
** Dabigatran (Pradaxa®) | |||
** Argatroban | |||
*** (NB! Not taken orally, so not technically a DOAC) | |||
* Direct factor X inhibitors | |||
** Apixaban (Eliquis®) | |||
** Rivaroxaban (Xarelto®) | |||
** Edoxaban (Lixiana®) | |||
* Antidotes | |||
** Idarucizumab (antidote to dabigatran) | |||
** Andexanet (antidote to apixaban and rivaroxaban) | |||
== Indications == | |||
DOACs can be used for most indications for anticoagulants, including [[stroke]] prevention in [[atrial fibrillation]] and prevention and treatment of [[venous thromboembolism]]. | |||
== Mechanism of action == | |||
These drugs bind to and inhibit certain clotting factors directly. Dabigatran and argatroban bind to and inhibit thrombin (factor IIa). Rivaroxaban, apixaban, edoxaban are factor Xa inhibitors. | |||
Idarucizumab is a monoclonal antibody which binds to and inactivates dabigatran. Andexanet is a modified recombinant factor Xa. Apixaban and rivaroxaban bind to andexanet with the same affinity as factor Xa, which frees up endogenous factor Xa. | |||
== Pharmacokinetics == | |||
DOACs are excreted renally, and so require dose adjustment in mild forms of kidney failure and possibly being contraindicated in severe forms. Dabigatran is renally excreted to a much larger degree than the factor Xa inhibitors. | |||
However, they’re also metabolised by the liver and so are also contraindicated in severe liver failure. | |||
== Contraindications == | |||
* Pregnancy | |||
* Mechanical [[prosthetic heart valve]] | |||
* Severe [[kidney failure]] | |||
* Severe [[liver failure]] | |||
* Extremes of body weight (very high or very low) | |||
** Requires dose adjustment in some DOACs and is contraindicated for others | |||
== Reversal == | |||
Idarucizumab and andexanet can be used to reverse their effect, but are not readily available and are quite expensive. They're mostly reserved for life-threatening haemorrhage. Transfusion of fresh frozen plasma (FFP) can also reverse their effect in theory, but the clinical value of doing this is uncertain. | |||
== Monitoring == | |||
<section begin="clinical biochemistry" />There is no routine monitoring of DOAC efficacy, as they have a predictable dose-effect relationship. Many labs can measure the serum level of the specific DOAC or the anti-factor Xa assay (a different assay from the one used for UFH/LMWH), but this does not correlate with therapeutic efficacy, only drug absorption. As such, monitoring is rarely indicated.<section end="clinical biochemistry" /> | |||
== Advantages of DOACs vs VKAs == | |||
* Don’t require regular monitoring | |||
* Lower bleeding risk | |||
== Disadvantages of DOACs vs VKAs == | |||
* Reversing their effect requires antidotes which are very expensive and not readily available | |||
* More expensive | |||
[[Category:Pharmacology]] | |||