Rivaroxaban Versus Vitamin K Antagonist in Antiphospholipid Syndrome - Rivaroxaban in Antiphospholipid Syndrome

Dec 20, 2019
Font Size
A
A
A
Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Bayer Hispania
Date Published:
11/19/2019
Date Updated:
12/20/2019
Original Posted Date:
12/20/2019
References

Contribution To Literature:

Rivaroxaban 20 mg daily did not meet criteria for noninferiority compared with VKAs for prevention of thrombotic events among patients with thrombotic APS.

Description:

The goal of the trial was to assess the safety and efficacy of rivaroxaban compared with vitamin K antagonists (VKAs) for preventing thrombotic events among patients with thrombotic antiphospholipid antibody syndrome (APS).

Study Design

Eligible patients with thrombotic APS were randomized in a 1:1 fashion to either rivaroxaban 20 mg daily (renal dose 15 mg) (n = 95) versus dose-adjusted VKAs (target international normalized ratio [INR], 2.0-3.0, or 3.1-4.0 in patients with a history of recurrent thrombosis) (n = 95).

  • Total screened: 234
  • Total number of enrollees: 190
  • Duration of follow-up: 33.1 months
  • Median patient age: 49 years
  • Percentage female: 61%

Inclusion criteria:

  • Objectively confirmed arterial or venous thrombosis and a positive result on aPL testing on two occasions at least 3 months apart
  • Lupus anticoagulant or moderate to high titers (≥40 GPL [immunoglobulin G {IgG} phospholipid] units) of IgG anticardiolipin, anti–2-glycoprotein I antibodies, or both, measured in accordance with international guidelines. Patients with only IgM subtypes were not eligible.

Exclusion criteria:

  • Significant bleeding diatheses (including refractory thrombocytopenia with a platelet count ≤50 × 109 cells/L)
  • Intracranial hemorrhage, stroke, or gastrointestinal bleeding within the previous 3 months
  • Pregnant or lactating
  • Severe renal impairment (creatinine clearance, calculated with the Cockcroft–Gault formula ≤30 ml/min/1.73 m2)
  • Alanine aminotransferase level more than twice the upper limit of normal
  • Child–Pugh class B or C cirrhosis
  • Nonadherent to their warfarin regimen
  • Taking cytochrome P450 3A4 inducers

Other salient features/characteristics:

  • Median duration of APS: 6.5 years
  • Clinical criteria for initial anticoagulation: venous thromboembolism (73%), arterial (37%), both (10%)
  • Recurrent thrombosis: 14%
  • Aspirin use: 13%

Principal Findings:

The primary endpoint, recurrent thrombosis for rivaroxaban vs. VKA, was 11.6% vs. 6.3% (relative risk 1.83, 95% confidence interval 0.71-4.76; p for noninferiority = 0.29; p for superiority = 0.20).

  • Arterial events: 10.5% vs. 3.2% (p = 0.06)
  • Venous events: 2.1% vs. 3.2% (p = 0.7)

Secondary outcomes for rivaroxaban vs. VKA:

  • Stroke: 10.5% vs. 0% (p = 0.05)
  • Major bleeding: 6.3% vs. 7.4% (p = 0.82)

Interpretation:

The results of this trial indicate that rivaroxaban 20 mg daily did not meet criteria for noninferiority compared with VKA for prevention of thrombotic events among patients with thrombotic APS. Recurrent arterial thrombotic events and stroke were higher with rivaroxaban compared with VKA. In the VKA group, recurrent events occurred primarily when INR was below therapeutic range. It is possible that higher anti-Xa activity may be necessary to prevent recurrent arterial events – direct oral anticoagulants are similarly not efficacious for patients with mechanical heart valves. This trial thus suggests that VKA may be the agent of choice for patients with thrombotic APS.

References:

Ordi-Ros J, Sáez-Comet L, Pérez-Conesa M, et al. Rivaroxaban Versus Vitamin K Antagonist in Antiphospholipid Syndrome: A Randomized Noninferiority Trial. Ann Intern Med 2019;171:685-94.

Editorial: Wahl D, Dufrost V. Direct Oral Anticoagulants in Antiphospholipid Syndrome: Too Early or Too Late? Ann Intern Med 2019;171:765-6.

Clinical Topics: Anticoagulation Management, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Valvular Heart Disease, Vascular Medicine, Anticoagulation Management and Venothromboembolism

Keywords: Anticoagulants, Antiphospholipid Syndrome, Aspirin, Heart Valve Diseases, Immunoglobulin G, Immunoglobulin M, International Normalized Ratio, Lupus Coagulation Inhibitor, Secondary Prevention, Stroke, Thrombosis, Venous Thrombosis, Venous Thromboembolism, Vitamin K, Warfarin, Vascular Diseases


< Back to Listings