Current Drug Therapy

Dabigatran: Will it change clinical practice?

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SPECIAL CONDITIONS

Switching from other anticoagulants to dabigatran

When making the transition from a subcutaneously administered anticoagulant, ie, a low-molecular-weight heparin or the anti-Xa inhibitor fondaparinux (Arixtra), dabigatran should be started 0 to 2 hours before the next subcutaneous dose of the parenteral anticoagulant was to be given.21,35

When switching from unfractionated heparin given by continuous intravenous infusion, the first dose of dabigatran should be given at the time the infusion is stopped.

When switching from warfarin, dabigatran should be started once the patient’s INR is less than 2.0.

Switching from dabigatran to a parenteral anticoagulant

When switching from dabigatran back to a parenteral anticoagulant, allow 12 to 24 hours after the last dabigatran dose before starting the parenteral agent.21,35

Elective surgery or invasive procedures

The manufacturer recommends stopping dabigatran 1 to 2 days before elective surgery for patients who have normal renal function and a low risk of bleeding, or 3 to 5 days before surgery for patients who have a creatinine clearance of 50 mL/min or less. Before major surgery or placement of a spinal or epidural catheter, the manufacturer recommends that dabigatran be held even longer.35

If emergency surgery is needed

If emergency surgery is needed, the clinician must use his or her judgment as to the risks of bleeding vs those of postponing the surgery.21,35

Overdose or bleeding

No antidote for dabigatran is currently available. It has a short half-life (12–14 hours), and the treatment for overdose or bleeding is to discontinue it immediately, maintain adequate diuresis, and transfuse fresh-frozen plasma or red blood cells as indicated.

The role of activated charcoal given orally to reduce absorption is under evaluation, but the charcoal must be given within 1 to 2 hours after the overdose is taken.21

Dabigatran does not bind very much to plasma proteins and hence is dialyzable—an approach that may be necessary in cases of persistent or life-threatening bleeding.

Recombinant activated factor VII or prothrombin complex concentrates may be additional options in cases of severe bleeding.18,21

TOPICS OF FUTURE RESEARCH

A limitation of the dabigatran trials was that they did not enroll patients who had renal or liver impairment, cancer, or other comorbidities; pregnant women; or children. Other topics of future research include its use in patients weighing less than 48 kg or more than 110 kg, its efficacy in patients with thrombophilia, in patients with mechanical heart valves, and in long-term follow-up and the use of thrombolytics in patients with acute stroke who are on dabigatran.

WILL DABIGATRAN CHANGE CLINICAL PRACTICE?

Despite some of the challenges listed above, we believe that dabigatran is likely to change medical practice in patients requiring anticoagulation.

Dabigatran’s biggest use will most likely be in patients with atrial fibrillation, mainly because this is the largest group of people receiving anticoagulation. In addition, the incidence of atrial fibrillation rises with age, the US population is living longer, and patients generally require life-long anticoagulation once this condition develops.

Dabigatran may be approved for additional indications in the near future. It has already shown efficacy in primary and secondary prevention of venous thromboembolism. Other important areas to be studied include its use in patients with mechanical heart valves and thrombophilia.

Whether dabigatran will be a worthy substitute for the parenteral anticoagulants (heparin, low-molecular-weight heparins, or factor Xa inhibitors) is not yet known, but it will have an enormous impact on anticoagulation management if proved efficacious.

If dabigatran becomes a major substitute for warfarin, it will affect the anticoagulation clinics, with their well-trained staff, that are currently monitoring millions of patients in the United States. These clinics would no longer be needed, and laboratory and technical costs could be saved. A downside is that patients on dabigatran will not be as closely supervised and reminded to take their medication as patients on warfarin are now at these clinics. Instead, they will likely be supervised by their own physician (or assistants), who will need to become familiar with this anticoagulant. This may affect compliance with dabigatran.

OTHER NEW ORAL ANTICOAGULANTS ARE ON THE WAY

Other oral anticoagulants, including rivaroxaban (Xarelto) and apixaban (Eliquis), have been under study and show promise in preventing both thrombotic stroke and venous thromboembolism. They will likely compete with dabigatran once they are approved.

Rivaroxaban, an oral direct factor Xa inhibitor, is being investigated for stroke prevention in patients with atrial fibrillation. It has also been shown to be not inferior to (and to be less expensive than) enoxaparin in treating and preventing venous thromboembolism in patients undergoing hip or knee arthroplasty.32,36,37 Rivaroxaban has recently been approved by the FDA for this indication.

Apixaban, another direct factor Xa inhibitor, is also being studied for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. To date, there are no head-to-head trials comparing dabigatran with either of these new oral anticoagulants.

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Proceedings of the 2010 Heart-Brain Summit

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