Less bleeding with rivaroxaban for venous thromboembolism

December 10, 2015

Studies involving more than 8,000 patients found that rivaroxaban beat out low-molecular-weight heparin/vitamin K antagonists with fewer and less challenging bleeding episodes.

A recent analysis of data from the EINSTEIN-DVT and EINSTEIN-PE trials showed that patients had fewer and less challenging bleeding episodes when treated with rivaroxaban than they did when treated with combined low-molecular-weight heparin/vitamin K  (LMWH/VKA) antagonists.

See also: Renal function decline common in patients treated with DOACs

These studies involved more than 8,000 patients assigned to receive either rivaroxaban or LMWH/VKA. Major bleeds were classified according to the severity of clinical presentation and clinical course. Rivaroxaban recipients experienced less major bleeding than LMWH/VKA recipients (HR 0.54; 95% CI, 0.37–0.79) as well as fewer severe clinical presentations (HR 0.35; P=0.006) and a less-severe clinical course (HR 0.46; P=0.04). Fresh-frozen plasma, red-cell transfusions, and prothrombin complex concentrates were given less often to rivaroxaban-treated patients than to LMWH/VKA-treated patients.

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Rivaroxaban inhibits only one clotting factor, whereas vitamin K antagonists decrease four clotting factors. Because of this and other differences, fewer bleeding complications might be anticipated with these agents than with older drugs such as warfarin. This study appears to support that hypothesis, which shows that not only the number of bleeds, but also their location, intensity, and required treatments are less challenging.

Source: Eerenberg ES, Middeldorp S, Levi M, et al. Clinical impact and course of major bleeding with rivaroxaban and vitamin K antagonists. J Thromb Haemost 2015;13:1590–1596.

PICCs increase thromboembolism risk

Peripherally inserted intravenous catheters (PICC) may increase the risk of upper-extremity deep venous thrombosis (DVT) nearly 10.5-fold. There has been marked increase over the past few years in the use of these devices because they terminate in the central veins and can be used to infuse antibiotics, deliver chemotherapy, and monitor hemodynamics. They lack the potential complications associated with placement of central venous catheters,; however, they come with their own complications, including upper-extremity DVT and pulmonary embolism (PE).

A recent data analysis of 3,790 patients with PICC lines found 876 thromboembolic events occurring in 774 patients. Overall, having a PICC was associated with a statistically significant risk for upper-extremity DVT, lower-extremity DVT, and PE. After adjustment for other risk factors, including hospitalization during the preceding year, diagnosis of cancer during the preceding year, and history of VTE, PICC use was independently associated with upper-extremity DVT and with lower-extremity DVT, but not with PE.

Source: Greene MT, Flanders SA, Woller SC, et al. The association between PICC use and venous thromboembolism in upper and lower extremities. Am J Med 2015; 128:986–983.

 

FDA approves reversal agent for dabigatran

FDA recently granted accelerated approval to idarucizumab (Praxbind) for use in patients taking dabigatran. The drug will be used in emergency situations when there is a need to quickly reverse dabigatran’s anticoagulant effects. Idarucizumab is the first reversal agent approved specifically for dabigatran and works by binding to the drug compound to neutralize its effect.

The safety and efficacy of idarucizumab were studied in three trials involving a total of 283 healthy volunteers taking dabigatran. In the subjects who were given idarucizumab, there was an immediate reduction in the amount of dabigatran in participants’ blood (measured as unbound dabigatran plasma concentration) that lasted for a period of at least 24 hours. In this study, the most common side effect from use of idarucizumab was headache.

Another trial included 123 patients taking dabigatran who received idarucizumab due to uncontrolled bleeding or because they required emergency surgery. In this ongoing trial, the anticoagulant effect of dabigatran was fully reversed in 89% of patients within four hours of receiving idarucizumab. In this study, the most common side effects were hypokalemia, confusion, constipation, fever, and pneumonia.

Reversing the effect of dabigatran exposes patients to the risk of blood clots and stroke from their underlying disease (such as atrial fibrillation). The idarucizumab labeling recommends that patients resume their anticoagulant therapy as soon as medically appropriate, as determined by their healthcare providers.

Source: FDA approves idarucizumab, the first reversal agent for the anticoagulant Pradaxa: Praxbind approved for specific emergency situations [press release]. http://bit.ly/praxbindfda. Published October 16, 2015. Accessed November 1, 2015.