Rivaroxaban and usual care had similar rates of recurrent VTE and bleeding in symptomatic PE

Witt DM. — Tue, 21 Aug 2012 00:00:00 GMT

Question

In patients with symptomatic pulmonary embolism (PE), what are the effects of rivaroxaban compared with usual care on recurrent venous thromboembolism (VTE) and bleeding?

Methods

Design

Randomized controlled trial (EINSTEIN–Pulmonary Embolism Study). ClinicalTrials.gov NCT00439777.

Allocation

Concealed.*

Blinding

Blinded* (outcome adjudication committee and {data analysts}†).

Follow-up period

Mean 9 months.

Setting

263 sites in 38 countries.

Patients

4833 adults (mean age 58 y, 53% men) with acute, symptomatic, objectively verified PE with or without symptomatic deep venous thrombosis (DVT). Exclusion criteria included low-molecular-weight heparin, fondaparinux, or unfractionated heparin for > 48 hours, or > 1 dose of a vitamin K agonist (VKA) before randomization; or another indication for VKA treatment.

Intervention

Oral rivaroxaban, 15 mg twice daily for 3 weeks and then 20 mg once daily (n = 2420); or usual care with enoxaparin, 1.0 mg/kg body weight twice daily (for ≥ 5 d until international normalized ratio [INR] was ≥ 2.0 for 2 consecutive d) plus a VKA (warfarin or acenocoumarol) started within 48 hours of randomization, with dose adjusted to maintain INR at 2.0 to 3.0 (n = 2413).

Outcomes

Primary efficacy outcome was symptomatic recurrent VTE (composite of fatal or nonfatal PE or DVT). Primary safety outcome was clinically relevant bleeding (composite of major or clinically relevant nonmajor bleeding). Secondary outcomes included major bleeding (clinically overt bleeding; decrease in hemoglobin level ≥ 2.0 g/dL; transfusion of ≥ 2 units of red cells; or if bleeding was intracranial or retroperitoneal, occurred in other critical sites, or contributed to death).

Patient follow-up

99.6% (intention-to-treat analysis).

Main results

The main results are in the Table. {Results are consistent with an absolute reduction in recurrent VTE with rivaroxaban of 5 per 1000 patients or an increase of 10 per 1000 patients, and a reduction in clinically relevant bleeding of 28 per 1000 patients or an increase of 7 per 1000 patients}‡.

Conclusion

Rivaroxaban and usual care had similar rates of recurrent venous thromboembolism and clinically relevant bleeding in patients with symptomatic pulmonary embolism.Rivaroxaban vs usual care for symptomatic pulmonary embolism§OutcomesRivaroxabanUsual careAt a mean 9 moRRI (95% CI)NNH (CI)Recurrent VTE2.1%1.8%12% (−25 to 67)NSRRR (CI)NNT (CI)Clinically relevant bleeding||¶10.3%11.4%9% (−7 to 23)NSMajor bleeding||**1.1%2.2%51% (21 to 69)92 (68 to 223)§NS = not significant; VTE = venous thromboembolism; other abbreviations defined in Glossary. RRI, RRR, NNH, NNT, and CI calculated from control event rates and hazard ratios in article. Analyses were adjusted for cancer at baseline.||Patients receiving ≥ 1 dose of study drug (n = 4817).¶Composite of major or clinically relevant nonmajor bleeding.**Clinically overt bleeding; decrease in hemoglobin level ≥ 2.0 g/dL; transfusion of ≥ 2 units of red cells; or if bleeding was intracranial or retroperitoneal, occurred in other critical sites, or contributed to death.

Annals of Internal Medicine: Pulmonary Embolism Topic Collection

Rivaroxaban and usual care had similar rates of recurrent VTE and bleeding in symptomatic PE