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Rivaroxaban noninferior to fondaparinux for superficial vein thrombosis
Patients with superficial vein thrombosis treated with rivaroxaban experienced similar rates of progression or recurrence, all-cause mortality and major bleeding events as those treated with fondaparinux, according to results of the SURPRISE clinical study.
“To our knowledge, these findings provide the first evidence that rivaroxaban is an effective alternative to parenteral anticoagulation for treatment of superficial vein thrombosis,” Jan Beyer-Westendorf, MD, from the Carl Gustav Carus Hospital in Germany, and colleagues wrote. “Rivaroxaban could offer such patients a less burdensome and less expensive option of a once-a-day oral treatment instead of treatment with a more expensive once-a-day subcutaneous injection,”
Superficial vein thrombosis is a common, painful disorder that may lead to deep vein thrombosis if left untreated. Guidelines recommend a 45-day course of fondaparinux, an indirect Factor Xa inhibitor. However, this agent is considered “inconvenient” due to the fact it is administered by subcutaneous injection daily.
Therefore, Beyer-Westendorf and colleagues compared efficacy and risk factors of fondaparinux with rivaroxaban (Xarelto, Janssen), an oral factor Xa inhibitor that does not require daily injection and is cheaper.
The researchers randomly assigned 472 patients to receive 10 mg oral rivaroxaban (n = 236; median age, 61 years; range, 51-73; 58% women) or 2.5 mg subcutaneous fondaparinux (n = 236; median age, 61 years; range, 50-70; 63% women) once a day for 45 days. All patients had symptomatic thrombosis and at least one additional risk factor.
“Our study is the first to prospectively study a direct oral anticoagulant, rivaroxaban, against fondaparinux in superficial vein thrombosis and to show noninferiority for rivaroxaban,” the researchers wrote. “SURPRISE is also the first study that prospectively assessed patients with superficial vein thrombosis at high-risk for thromboembolic complications.”
The primary efficacy outcome of the study was a composite of symptomatic DVT or pulmonary embolism, progression or recurrence of superficial vein thrombosis, and all-cause mortality at 45 days in the per-protocol population.
The mean duration of treatment was 43.7 days (standard deviation, 7.4) in the rivaroxaban group and 44.8 days (standard deviation, 3.9) in the fondaparinux group.
Among 435 patients included in the per-protocol analysis, the primary efficacy outcome occurred in seven of 211 patients (3%; 95% CI, 1.6-6.7) treated with rivaroxaban compared with four of 224 patients (2%; 95% CI, 0.7-4.5) treated with fondaparinux after 45 days, suggesting noninferiority (HR = 1.9; 95% CI 0.6–6.4).
At 90 days, the primary efficacy outcome occurred in seven percent of patients in both groups (HR = 1.1; 95% CI, 0.5-2.2).
No major bleeds occurred in either group. Nonmajor bleeding occurred in six of 236 patients (3%) treated with rivaroxaban and one of 235 patients (< 1%) treated with fondaparinux (HR = 6.1; 95% CI, 0.7-50.3). One patient died in the rivaroxaban group due to cardiogenic shock 50 days after a type A aortic dissection, which was not treatment related.
This study suggests that rivaroxaban is a “more practical” alternative for treatment than fondaparinux, Walter Ageno, MD, and Francesco Dentali, MD, from the department of medicine and surgery at University of Insubria in Italy, wrote in a related editorial.
“This treatment has obvious practical advantages potentially improving patients’ quality of life,” Ageno and Dentali wrote.
Unlike the previous CALISTO trial, Ageno and Dentali noted there was increasing incidence of VTE between day 45 and day 90 in both study arms of the SURPRISE trial, from 3% to 7% in the rivaroxaban group and from 2% to 7% in the fondaparinux group.
“It is unlikely that this difference can be simply explained by the fact that follow-up in the SURPRISE study was about 2 weeks longer than in the CALISTO study,” they wrote. “This finding suggests the possibility that in selected higher-risk patients a longer duration of
anticoagulant treatment might be warranted.
“These results need to be confirmed by other studies in this setting, with particular focus on selected higher risk patients (eg, patients with cancer) for whom higher doses might be more effective,” they added. – by Melinda Stevens
Disclosures: Beyer-Westendorf reports research support and honoraria from Bayer, Boehringer Ingelheim, Daiichi Sankyo, LeoPharma and Pfizer. Please see the full study for a list of all other researchers’ relevant financial disclosures. Ageno reports advisory board roles with and honoraria or research funding from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb and Daiichi Sankyo. Dentali reports advisory board roles with and honoraria or research funding from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb and Daiichi Sankyo.