Treating DVT: Answers to 7 key questions
Complex recommendations for anticoagulant therapy raise questions for family physicians. Here are the evidence-based answers you need to manage DVT patients successfully.
Three studies, RE-MOBILIZE, RENOVATE, and RE-MODEL, compared dabigatran’s efficacy and safety with enoxaparin for the prevention of VTE after knee and hip replacement surgery. In the RE-MOBILIZE trial, dabigatran was effective compared with enoxaparin once daily, but not effective compared with twice-daily enoxaparin.16 The RE-NOVATE and RE-MODEL studies also showed dabigatran’s efficacy compared with once-daily enoxaparin.17-19 Major bleeding occurred in approximately 1% of patients in both the dabigatran and enoxaparin treatment groups, and the incidence of hepatotoxicity was similar.17-19
The RE-LY trial studied warfarin vs 2 different doses of dabigatran in atrial fibrillation for the prevention of stroke or systemic embolism. Both doses of dabigatran (110 mg twice daily or 150 mg once daily) were similar to warfarin for the study’s primary outcome, and dabigatran at the 110-mg dose had a significantly lower incidence of hemorrhagic stroke.19 Studies on the use of dabigatran in acute coronary syndrome are ongoing.
Apixaban and rivaroxaban are oral inhibitors of both free and fibrin-bound factor Xa. They are similar in activity to the currently available, injectable fondaparinux. In the RECORD 1, 2, 3, and 4 trials, rivaroxaban was compared with once- or twice-daily enoxaparin in patients undergoing hip and knee replacement surgery.20 Rivaroxaban was significantly better in preventing VTE and it had a comparable rate of major bleeding (approximately 0.2%). Rivaroxaban has been approved in Canada and Europe for thromboprophylaxis after major orthopedic surgery. Rivaroxaban was recommended for approval by an FDA advisory panel, but the FDA has not issued an approval as yet.
Phase III trials for other indications of rivaroxaban and apixaban are currently underway. The long-term safety and adverse event profiles are as yet unclear. If and when these new medications are approved, they should be used judiciously while issues related to reversibility, long-term adverse events, and monitoring are still unresolved. For some patients, warfarin may continue to be the most appropriate oral anticoagulant medication.
Your patient, a 64-year-old man, has a 4-day history of warmth and tenderness in his right calf. Two weeks earlier, he had knee replacement surgery. he left the hospital with a prescription for enoxaparin (Lovenox) 30 mg every 12 hours for 5 days (for a total of 10 doses), but he tells you that he did not get the prescription filled because of the cost. (Even with the copay, it was more than he thought the medication was worth.)
Your clinical diagnosis is a deep vein thrombosis (DVT), and this is confirmed by a venous Doppler ultrasound study showing a clot extending from the popliteal to the femoral vein. He has no signs of a pulmonary embolism (PE), no shortness of breath or chest pain, and according to your office PE prediction calculator, his probability of PE is low. He doesn’t want to go back to the hospital for treatment, and you agree that he is capable of managing his condition at home. At a weight of 98 kg, he isn’t obese and his serum creatinine and complete blood count are within normal limits.
Q How would you treat this patient?
You decide to start the patient on enoxaparin 100 mg subcutaneously every 12 hours. You teach him proper injection technique and write a prescription for 10 syringes with 1 refill. He now understands that the medication is essential and is ready to cover the copay. You also start him on warfarin 5 mg daily. You explain that when he is taking warfarin, he needs to have his blood clotting time tested frequently. He’ll need a lab test of his international normalized ratio (INR) on Day 3 and Day 5 of warfarin. If the INR is ≥2 after 5 days, he can stop enoxaparin therapy. If the INR is <2 on Day 5, he will need to continue enoxaparin until the INR is ≥2.
On Day 5, your patient’s INR is 2.5, so you tell him to stop taking enoxaparin and continue regular INR testing, getting his next test within 1 week of this office visit. His INR remains stable for 3 months on 5 mg warfarin daily. Then you get a call from the lab, telling you the patient’s INR is elevated at 4.2.
Q What could be causing your patient’s INR to be elevated?
You call the patient and ask if he has been taking his medication faithfully and whether he has been eating normally. You also ask whether he has started any new medications.
He tells you he has been taking his warfarin and hasn’t made any changes in his diet, but he is on the last day of a 7-day treatment with metronidazole for pseudomembranous colitis. He says he has had no bleeding and has not noticed any large bruises or dark stools. The elevated INR is probably a drug interaction with the metronidazole. You tell him to skip his warfarin for 1 night and then have his INR rechecked. The next day, the INR is back in the normal range. He continues on warfarin therapy. His INR remains stable and his leg pain does not recur.
