The classical anticoagulants
Risk factor | Points |
---|---|
Age 65–75 years | 1 |
Age over 75 years | 2 |
Female gender | 1 |
Coronary or peripheral artery disease | 1 |
Previous stroke | 2 |
Hypertension | 1 |
Symptoms or signs of left ventricular dysfunction | 1 |
Diabetes mellitus | 1 |
The new oral anticoagulants
Class | Name | T ½ (h) | Dosing | Excretion |
---|---|---|---|---|
Anti-IIa (antithrombin) | Dabigatran (PradaxaR) | 7–9 | b.i.d. | 80 % kidney, 20 % liver |
Anti-Xa | Apixaban (EliquisR) | 8–15 | b.i.d. | 21 % kidney, 78 % liver |
Rivaroxaban (XareltoR) | 9–12 | qd | 33 % kidney, 66 % liver | |
Edoxaban (LixianaR)a
| 8–10 | qd | 35 % kidney, 65 % liver |
Class | Advantages | Disadvantages |
---|---|---|
Oral direct IIa/Xa blockers | More effective against thromboembolism than VKA | No monitoring in case of bleeding or urgent surgery |
Fast onset of action | Not applicable in severe renal failure (CrCl < 30 ml/min) | |
Fast offset of action (in case of bleeding/surgery) | Not applicable in carriers of artificial heart valves | |
Better safety, especially less intracranial bleeding than VKA | Short duration of action (thrombosis risk with poor compliance | |
Ease (no monitoring) | Antidote strategy not established | |
Some agents have interaction with anti-arrhythmic agents | ||
Vitamin K antagonists | Therapeutic window established | Monitoring of INR |
Antidote algorithm established | Drug interaction with many agents | |
Long duration of action | Food interaction | |
(low thrombosis risk with poor compliance) | Slow onset of action | |
High bleeding risk, intracranial bleeding in particular |
The trials and registries
Class | Name | Comparator | Design |
n
| Trial |
---|---|---|---|---|---|
Anti-IIa (antithrombin) | Dabigatran | Warfarin (clinic) | Open | 18,133 | RE-LY [12] |
Anti-Xa | Apixaban | Warfarin (point of care) | Double-blind | 14,264 | ROCKET-AF [19] |
Rivaroxaban | Warfarin (point of care) | Double-blind | 18,201 | ARISTOTLEF [20] | |
Edoxaban | Warfarin (point of care) | Double-blind | > 21,000 | ENGAGE AF TIMI-48a
|
Introduction of the new oral anticoagulants
Organisation | A local protocol for handling of bleeding and/or surgery must be written |
Prescription | Fill out the doctor’s statement and explain transition if the patient is on VKA |
Renal function | Creatinine clearance should be more than 30 ml/min |
Transition | Stop VKA and wait for the INR to be < 2.0 before starting NOAC |
Elective major procedure | Stop NOAC 24–48 h ahead according to renal function, no bridging |
Elective minor procedure | Consider NOAC continuation |
Minor bleeding | Consider NOAC continuation |
Moderate bleeding | Skip one NOAC dose and perform haemostasis |
Major bleeding | Stop NOAC, perform haemostasis and consider CofactR and/or CyclokapronR
|
Life-threatening bleeding | All of the above and consider NovosevenR
|
Reporting of bleeding | Severe bleeding must be reported to Lareb Monitoring Program (www.lareb.nl) |