Management of thrombophlebitis: are the new anticoagulant drugs useful?
From time to time, I have to manage patients with thrombophlebitis. The most effective drug for this has been Fondaparinux (a synthetic low molecular weight heparin) which moderates symptoms if given daily for about 6 weeks. Alternatively, low molecular weight heparins may be used for the same duration. This strategy is supported by ACCP Guidelines and by a Cochrane review.
The problem is that these drugs can only be given by daily injections. Many patients are a little reluctant to agree to this regime. In the last decade, several of the newer oral anticoagulant drugs have been licensed for the prevention and treatment of venous thrombo-embolism. I have recommended these to my patients for some time in order to prevent DVT after varicose veins treatments in high risk patients. Published guidelines have not recommended any of this group of drugs for the treatment of thrombophlebitis since no clinical trial had been done.
A recently published paper in the Lancet addresses this issue in a randomised clinical trial. Fondaparinux and rivaroxaban were compared in a study which concluded that they were equally effective. The oral anticoagulant drug is less expensive than Fondaparinux or heparin injection and more acceptable to patients. Oral rivaroxaban looks as though it will be the definitive treatment for thrombophlebitis in the future.
Philip Coleridge Smith, Consultant Vascular Surgeon
Abstract
Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the open-label, randomised, non-inferiority SURPRISE phase 3b trial.
Beyer-Westendorf J, Schellong SM, Gerlach H, Rabe E, Weitz JI, Jersemann K, Sahin K, Bauersachs R; SURPRISE investigators.
Lancet Haematol. 2017 Mar;4(3):e105-e113. doi: 10.1016/S2352-3026(17)30014-5.
Summary
Background
Superficial-vein thrombosis can lead to deep-vein thrombosis and pulmonary embolism. Rivaroxaban, an oral factor Xa inhibitor, might simplify treatment compared with fondaparinux because it does not require daily subcutaneous injection and is cheaper. We compared efficacy outcomes in patients with superficial-vein thrombosis and additional risk factors given either rivaroxaban or fondaparinux to assess whether rivaroxaban is non-inferior to fondaparinux in the prevention of thromboembolic complications.
Methods
In this open-label, masked endpoint, randomised, non-inferiority phase 3b trial, we recruited patients aged 18 years or older with symptomatic superficial-vein thrombosis from 27 sites (academic, community hospitals, and specialist practices) in Germany. We randomly assigned patients (1:1) to receive 10 mg oral rivaroxaban or 2·5 mg subcutaneous fondaparinux once a day for 45 days. Patients were eligible if they had symptomatic thrombosis (at least 5 cm in a supragenual superficial-vein segment) and at least one additional risk factor (older than 65 years, male sex, previous venous thromboembolism, cancer, autoimmune disease, thrombosis of non-varicose veins). Main exclusion criteria were: symptoms for longer than 3 weeks, thrombus within 3 cm of the sapheno-femoral junction, indication for full-dose anticoagulation therapy, and substantial hepatic or renal impairment. Randomisation was done with a central block randomisation process. The primary efficacy outcome was a composite of symptomatic deep-vein thrombosis or pulmonary embolism, progression or recurrence of superficial vein-thrombosis, and all-cause mortality at 45 days in the per-protocol population (all randomly assigned patients without major protocol violations). We used a non-inferiority margin of 4·5% (absolute difference between rivaroxaban and fondaparinux). The main safety outcome was major bleeding. This study is registered with ClinicalTrials.gov, number NCT01499953.
Findings
Between April 25, 2012, and Feb 18, 2016, 485 patients were enrolled in the study and 472 were randomly assigned to the rivaroxaban group (n=236) or the fondaparinux group (n=236). In the 435 patients included in the per-protocol analysis set, the primary efficacy outcome occurred in seven (3%) of 211 patients (95% CI 1·6–6·7) in the rivaroxaban group and in four (2%) of 224 patients (0·7–4·5) in the fondaparinux group (hazard ratio [HR] 1·9, 95% CI 0·6–6·4; p=0·0025 for non-inferiority) at day 45. There were no major bleeds in either group. There was one death in the rivaroxaban group; this patient died from cardiogenic shock on day 50 after a type A aortic dissection, not related to treatment.
Interpretation
Rivaroxaban was non-inferior to fondaparinux for treatment of superficial-vein thrombosis in terms of symptomatic deep-vein thrombosis or pulmonary embolism, progression or recurrence of superficial vein-thrombosis, and all-cause mortality, and was not associated with more major bleeding. Therefore, rivaroxaban could offer patients with symptomatic superficial-vein thrombosis a less burdensome and less expensive oral treatment option instead of a more expensive