Xarelto vs Warfarin in patients with anti-phospholipid syndrome

Xarelto vs Warfarin - Rivaroxaban (Xarelto, Roxarel, Rivoban) is a novel anticoagulant that blocks the coagulation pathway by inhibiting Factor X. Warfarin inhibits the synthesis of vitamin K dependent factors. Xarelto is commonly being used for a variety of indications.

Following are the approved indications where it may be used:

  1. Treatment of deep vein thrombosis and pulmonary embolism.
  2. Prevention of thromboembolism in patients with non-valvular atrial fibrillation
  3. Prevention of deep vein thrombosis in patients with a total knee replacement or hip arthroplasty
  4. Prevention of DVT recurrence in patients who have been treated with a full dose of anticoagulants for six months and are at risk of recurrence.
  5. In patients with coronary artery disease or peripheral arterial disease.

Xarelto vs warfarin - Xarelto is inferior to warfarin in patients with antiphospholipid syndrome!

A study published in the Annals of Internal Medicine recently has shown that rivaroxaban is inferior to warfarin in patients with antiphospholipid syndrome. The study was conducted in six university hospitals in Spain over a period of three years. A total of 190 patients were enrolled in the study aged 18 to 75 years with thrombotic antiphospholipid syndrome. Participants were given dose-adjusted warfarin to a target INR of 2.0 - 3.0 or 3.1 - 4.0 in patients with recurrent thrombosis or rivaroxaban at a dose of 20 mg daily or 15 mg daily in patients with deranged renal functions. After a follow-up of 3 years, recurrent thrombosis was seen in 11 percent in the rivaroxaban group compared to 6% in the warfarin group. Major bleeding episodes were similar in both groups. The incidence of stroke was more common in patients using rivaroxaban.

This is a Co-incidence!

Yesterday, I wrote this article and today I saw a patient of recurrent deep vein thrombosis. She was a young female who had bilateral DVT 17 years back and was treated. During her pregnancy, she developed cortical vein thrombosis followed by seizures and was again treated with rivaroxaban. One year back, she developed bilateral deep vein thrombosis again and was started on rivaroxaban which she took for one year. Initially, the DVT started resolving, however, while on treatment, her symptoms reappeared and she visited us in the OPD today. We advised her an autoimmune profile, thrombophilia screening, and work-up for antiphospholipid antibody syndrome. She was switched to warfarin and was advised to continue it lifelong.

Results of our study conducted in PIMS titled "Oral rivaroxaban in symptomatic deep vein thrombosis"

This study compared warfarin and rivaroxaban in patients with symptomatic deep vein thrombosis. Vessel patency was seen at the end of three months and six months via a doppler ultrasound. Overall, patients in the rivaroxaban group had better results, however, analysis of a subgroup of patients on warfarin who had an INR greater than 2.0 were analyzed separately. Patients on warfarin who had an INR greater than 2.0 had better results than rivaroxaban in terms of vessel patency.

Xarelto vs Warfarin - The advantages and disadvantages of Xarelto?

Rivaroxaban is preferred over warfarin for the following reasons:
  1. The risks of major bleeding episodes are less:
    • Most studies have proved that the risks of major bleeding are less compared to warfarin.
    • Minor bleedings like epistaxis and gum bleeding may be seen in both warfarin and rivaroxaban.
  2. Monitoring of INR is not required with Rivaroxaban:
    • Rivaroxaban is given in fixed doses with no monitoring required compared to warfarin which requires regular monitoring of INR.
    • Some experts believe that this is not a plus point as the treating physician is not sure whether anticoagulation is adequate or not.
    • Case reports of major bleeding episodes especially intracranial bleeds have been reported.
    • We have seen several patients in our ward getting admitted due to rivaroxaban induced intracranial bleeds (in contrast to what the studies show).
    • Similarly, many patients have DVT recurrence with rivaroxaban and are then switched to warfarin.
  3. Less drug-drug interaction with rivaroxaban:
    • Probably, this is the only and the major advantage of rivaroxaban.
    • Warfarin has got a lot of drug-drug interactions and interactions with foods especially healthy green and leafy vegetables and green tea.
    • In contrast to warfarin, rivaroxaban does not have such interactions and the diet does not need any adjustments.
  4. Xarelto is costly:
    • One tablet of Xarelto 2.5 mg costs about $8, while each 10 mg, 15 mg, and 20 mg tablet costs around $17.
    • In contrast to Xarelto, one 5 mg of warfarin tablet costs less than half a dollar.
  5. Antidote issue:
    • The antidote of warfarin i.e. vitamin K is easily available and very cheap.
    • Andexate alpha, the antidote of Rivaroxaban, has limited availability and is too costly.

In conclusion ...

High-risk patients with recurrent thrombosis should be preferably on warfarin with frequent monitoring of INR. Like patients with mechanical prosthetic valves, rivaroxaban should also be avoided in patients with the antiphospholipid syndrome with thrombotic events.
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