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Switch from LMWH to dabigatran prevents VTE after orthopedic surgery
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Switching patients from low–molecular-weight heparin to dabigatran after total hip or knee replacement surgery was shown to be effective for the prevention of venous thromboembolism, as well as safe, according to recent findings published in Thrombosis Journal.
“Without thromboprophylaxis, major orthopedic surgery, such as total hip or knee replacement, carries a high risk of [VTE] events, which manifests as deep vein thrombosis in two-thirds and as pulmonary embolism in approximately one-third of patients,” the researchers wrote. “This is because orthopedic surgery induces local and systemic thrombin generation, which can trigger thrombus formation and thrombotic events. … Effective anticoagulation significantly reduces the risk of VTE and is recommended in various international consensus guidelines.”
In the multicenter, open-label, prospective, single-arm study, researchers evaluated 168 patients who underwent elective primary total hip replacement (n = 81) or total knee replacement (n = 87) at one of seven orthopedic centers in Austria. Patients were started on an initial low–molecular-weight heparin (LMWH; enoxaparin) 40 mg daily for the prevention of VTE events. Enoxaparin was started before or after total hip or knee replacement surgery based on the clinical judgment of the investigator, and this treatment was switched to dabigatran (Pradaxa, Boehringer Ingelheim) 220 mg once daily at a time point also determined by the investigator. The researchers defined the study’s primary safety variable as major bleeding events from the last administration of enoxaparin until 24 hours after the last treatment with dabigatran. The co-primary efficacy endpoint was the composite of symptomatic VTE and all-cause mortality, also from the last administration of enoxaparin until 25 hours after last dosage of dabigatran.
Of the 168 patients enrolled in the study, 161 received both enoxaparin and dabigatran, two were treated with dabigatran only, and five received enoxaparin only. The majority of treated patients (82.6%) initiated oral dabigatran 22 to 26 hours after the final dose of enoxaparin, and most (88.7%) began oral dabigatran at least 24 hours postoperatively. The median time from final enoxaparin dose to initial dabigatran dose was 24 hours (range, 4-48 hours). Patients remained on dabigatran for a median of 36 days, which was similar for patients who underwent total hip replacement (median, 35.5 days) and total knee replacement (median, 37 days). No incidences of symptomatic VTE or all-cause mortality were reported at any time during the study, yielding an estimated incidence for the composite efficacy endpoint of 0% (95% CI, 0-2.24). There was only one occurrence of the primary safety variable (major bleeding event from last administration of enoxaparin until 24 hours after last administration of dabigatran). This bleeding event was at the surgical site and required treatment discontinuation after total knee replacement, but did not result in a significant drop in hemoglobin or necessitate transfusion. The event led to an estimated major bleeding event incidence of 0.61% (95% CI, 0.02-3.37). Very few bleeding events were reported overall; from last treatment with enoxaparin until 24 hours after last dose of dabigatran, minor bleeding events occurred in three additional patients. During dabigatran treatment, at least one adverse event occurred in 44 (27%) patients; of these, 13 (8%) led to cessation of dabigatran. Serious adverse events during dabigatran treatment occurred in four patients (2.5%).
“This study addressed the feasibility of switching from the LMWH, enoxaparin, to oral therapy with dabigatran, and closed a gap that has not been investigated in detail in phase 3/4 clinical trials for dabigatran in orthopedic surgery,” the researchers concluded. “The switching procedure did not raise any new safety issues or efficacy problems. The observed [adverse events] were consistent with the known safety profile of dabigatran.” – by Jennifer Byrne
Disclosure: One of the researchers was a full-time employee with Boehringer Ingelheim and is currently an employee of Novartis.
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