EINSTEIN DVT: efficacy and safety of rivaroxaban in the treatment of deep vein thrombosis
met its primary efficacy
endpoint and showed that a single-drug approach with oral rivaroxaban was at least as effective as (non-inferior to) conventional dual-drug therapy (subcutaneous enoxaparin plus vitamin K antagonist [VKA] followed by VKA
alone), with a similar safety profile, for the treatment of acute, symptomatic deep vein thrombosis
There was a significant improvement in the net clinical benefit for rivaroxaban compared with enoxaparin/VKA, achieved via a significant reduction in recurrent venous thromboembolism
and a numerically lower incidence of major bleeding.
In conclusion, EINSTEIN DVT
demonstrated that a fixed-dose regimen of oral rivaroxaban offers an effective and convenient single-drug alternative, with reassuring safety, to the current standard of care of dual-drug therapy for the treatment of acute DVT
Patients were well matched in both study arms, with similar demographic and clinical characteristics:
- Mean age: ~56 years
- ~57% were male
- ~83% had a body weight of >50 to 100 kg
- ~69% had creatinine clearance ≥80 ml/min, with a further 23% classified as having mild renal impairment (creatinine clearance 50–79 ml/min)
- ~19% had experienced a previous venous thromboembolic event before the acute, symptomatic DVT that qualified them for inclusion in the study
Primary efficacy endpoint: single-drug therapy with rivaroxaban was non-inferior to dual-drug therapy with enoxaparin plus VKA for the treatment of acute DVT
The primary efficacy
outcome occurred in 36/1731 (2.1%) patients treated with rivaroxaban, compared with 51/1718 (3.0%) patients treated with enoxaparin/VKA (p<0.001 for non-inferiority); there was a trend towards superiority for rivaroxaban.
Safety outcome: similar rates of bleeding with rivaroxaban and enoxaparin/VKA
Rivaroxaban was well-tolerated by patients in EINSTEIN DVT
, and the rate of major or non-major clinically relevant bleeding was similar to that for enoxaparin plus VKA
followed by VKA
Rivaroxaban provides superior net clinical benefit
A key secondary endpoint in the study was net clinical benefit; defined as the composite of the primary efficacy
endpoint and major bleeding.
- The net clinical benefit outcome occurred in 51/1731 (2.9%) patients who received rivaroxaban compared with 73/1718 (4.2%) patients who received enoxaparin/VKA (hazard ratio 0.67; 95% confidence interval 0.47–0.95; p=0.03)
Adverse event rates were similar in the two treatment groups during the treatment period
- 96 - The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499–2510.
- The ability of a drug to produce the desired effect.
- Formation of a clot inside a blood vessel.
- Deep vein thrombosis
- A blood clot in a deep vein, usually resulting from damage to the vein or blood flow slowing down or stopping. Usually DVTs are found in the leg, but can also be in the arm.
Distal DVTs are found in deep veins of the calf, and are the most common type of DVT.
Proximal DVTs are found in the legs above the calf muscle up to the waist.
- Vitamin K antagonist
- An anticoagulant that inhibits multiple steps in the blood clotting process. Administered orally, the dose varies by patient, and regular monitoring and dose adjustment is required. Vitamin K antagonists have interactions with food and other drugs. Due to the many limitations of this drug, many patients are actually not treated and many of those who are treated are outside of the required target INR range, which can be the cause for increased bleeding or a greater risk of stroke.
- Venous thromboembolism
- A disease process beginning with a blood clot occurring within the venous system, including deep vein thrombosis and pulmonary embolism.
- Pulmonary embolism
- A potentially fatal condition caused by a blood clot blocking a vessel in the lung: usually the clot originates from a DVT in the legs. PE can result in permanent lung damage.