DECEMBER 13, 2010
Anna D. Garrett, PharmD, BCPS, CPP
Pradaxa 101: The Basics of Dabigatran Therapy
Dabigatran etexilate (Pradaxa) was approved by the full FDA in mid- October with an indication for use in patients with atrial fibrillation. There are 2 dosing regimens that are approved. For patients with normal renal function, the approved dose is 150 mg twice daily. For patients with a creatinine clearance between 15 and 30 mL/min, the approved dose is 75 mg twice daily (there are no clinical trials using this dose).
Dabigatran provides a number of advantages for patients. These include:
• Improved outcomes if international normalized ratio control is poor
• No monitoring
• No known food–drug interactions
• A limited number of drug interactions. According to the package insert, only rifampin should be “generally avoided.” Interactions are related to induction or inhibition of P-glycoprotein. Other drugs listed for potential interactions include ketoconazole, verapamil, amiodarone, quinidine, and clarithromycin
Despite these advantages, there are several considerations that may make dabigatran less appealing for use in some patient populations. These include:
• There is no way to monitor adherence. Patients with a history of nonadherence who are at high risk of stroke may be poor candidates for this therapy
• There is no reversal agent in the event of an overdose or severe bleeding event
• Cost is expected to be $6.75 per day (acquisition cost), which may make it prohibitive for some patients
• Twice-a day-dosage regimen may lead to adherence problems
• Patients need periodic monitoring of creatinine clearance and liver function test
• Increased incidence of dyspepsia compared with warfarin (11.3% vs 5.8%, respectively)
• Should not be used in patients with creatinine clearance <15 mL/min
• Surgery can be performed after holding for 2 doses
Unprovoked Venous Thromboembolism Confers High Risk of Recurrence
A recent review of studies looking at the risk of recurrent venous thromboembolism (VTE) showed that patients who had an unprovoked VTE had the highest risk of recurrence.
This meta-analysis included prospective cohort studies and randomized trials of patients with a first episode of symptomatic VTE provoked by a transient risk factor and treated for at least 3 months.
The annualized rate of recurrence at 24 months was 3.3% per patient-year for all patients with a transient risk factor, 0.7% per patient-year in the subgroup with a surgical factor, and 4.2% per patient-year in the subgroup with a nonsurgical factor. In the same studies, the rate of recurrence after unprovoked VTE was 7.4% per patient-year.
The authors concluded that the risk of recurrence is low if VTE is provoked by surgery, intermediate if provoked by a nonsurgical risk factor, and high if unprovoked. These risks affect whether patients with VTE should undergo short-term or indefinite treatment.
Elevated C-Reactive Protein and Early Stroke-Related Deep Venous Thrombosis
A study presented at the European Federation of Neurological Societies in September showed that stroke patients who have an elevated C-reactive protein (CRP) at onset of the event have a higher risk of developing deep venous thrombosis (DVT), and could benefit from DVT prophylaxis.
The study enrolled 299 patients who were admitted for acute ischemic (92.8%) or hemorrhagic stroke. Prestroke comorbidities, neurological deficit at baseline (measured by National Institutes of Health Stroke Scale), and baseline CRP level were collected. DVT development was monitored by ultrasound and was performed twice—the first time within 7 days poststroke, and subsequently between days 8 and 10.
At the first poststroke evaluation, DVT was discovered in 8.0% of patients; it was discovered in 10.7% of the patients at the second evaluation. Newly developed DVT was determined to be present in 3.0% of patients, and was predominantly distal (7 of 9 cases).
The presence of DVT increased the risk of 3-month mortality, but did not alter the combined risk of dependency and death.
The authors suggest use of additional DVT prophylaxis in patients with high CRP levels.
Dr. Garrett is manager of the Health Education Center at Mission Hospitals in Asheville, North Carolina. Coagulation Counseling