Low-risk patients with VTE unlikely to bleed when assigned rivaroxaban

Issue: December 25, 2015

LONDON — Low-risk patients with venous thromboembolism have a less than 1 in 100 chance of experiencing a major bleeding event if they take rivaroxaban, according to findings presented at the European Society of Cardiology Congress.

For the purpose of the study, low-risk patients were defined as those younger than 65 years with no history of bleeding and no significant comorbidities, Jeffrey A. Kline, MD, from the department of emergency medicine at Indiana University School of Medicine, Indianapolis, said during a presentation.

Jeffrey A. Kline

Kline and colleagues conducted a secondary analysis of the EINSTEIN DVT+PE study of rivaroxaban (Xarelto, Janssen Pharmaceuticals) as a treatment for patients with deep vein thrombosis or pulmonary embolism. They analyzed bleeding risk in patients assigned rivaroxaban, who took a 15-mg dose twice a day for 21 days and then a 20-mg dose once a day for 3 to 12 months.

The primary outcome was 30-day and total treatment duration incidence of major or clinically relevant nonmajor bleeding. Kline and colleagues defined major bleeding as clinically overt bleeding that contributed to a drop in hemoglobin of at least 2 g/dL and led to transfusion of at least two units of red blood cells; intracranial bleeding or bleeding in another critical site; or bleeding that contributed to death. They defined clinically relevant nonmajor bleeding as that which did not meet the criteria for major bleeding but led to medical intervention, unscheduled physician contact, stopping the study drug temporarily or permanently, or discomfort or impairment of daily life activities.

They applied four clinical scoring systems derived to predict bleeding in patients with VTE taking vitamin K antagonists — Beyth et al (1998), Kuijer et al (1999), Landefield et al (1989) and Ruiz-Gimenez et al (2008) — to those treated with rivaroxaban in EINSTEIN DVT+PE. In all four, those at low risk for bleeding had a 6-month major bleeding rate of less than 2% while on vitamin K antagonists; Kline and colleagues hypothesized that the major bleeding rate reflected in all four systems in low-risk patients would be less than 1%.

Kline said the major bleeding rates in low-risk patients by different scoring systems were as follows:

Beyth et al: 30 days, 0.2%; 95% CI, 0.1-0.5; entire study period, 0.4%; 95% CI, 0.2-0.8;
Kuijer et al: 30 days, 0.3%; 95% CI, 0.1-0.7; entire study period, 0.3%; 95% CI, 0.1-0.9;
Landefield et al: 30 days, 0.3%; 95% CI, 0.1-0.6; entire study period, 0.5%; 95% CI, 0.2-0.8; and
Ruiz-Gimenez et al: 30 days, 0.2%; 95% CI, 0.1-0.4; entire study period, 0.5%; 95% CI, 0.2-0.7.

“This held up for patients treated for [PE] and [DVT],” he said.

He said the rates of clinically relevant nonmajor bleeding for low-risk patients in each system were as follows:

Beyth et al: 30 days, 3.5%; 95% CI, 2.7-4.2; entire study period, 7.1%; 95% CI, 5.6-7.7;
Kuijer et al: 30 days, 2.6%; 95% CI, 1.7-3.6; entire study period, 5.5%; 95% CI, 4-6.6;
Landefield et al: 30 days, 3.7%; 95% CI, 2.9-4.4; entire study period, 7.3%; 95% CI, 5.8-7.8; and
Ruiz-Gimenez et al: 30 days, 3.4%; 95% CI, 2.7-4.1; entire study period, 6.9%; 95% CI, 5.9-7.8.

“Patients with VTE aged less than 65 with no bleeding history and no significant comorbidities can be counseled that they have a less than 1 in 100 chance of experiencing a major bleeding event during the course of treatment with rivaroxaban,” Kline said. – by Erik Swain

Reference:

Kline JA, et al. Clinical Trial Update II – Antiplatelet Therapy. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 2, 2015; London.

Disclosures: The EINSTEIN DVT+PE study was funded by Janssen Pharmaceuticals. Kline reports receiving research funding from the NIH and Ikaria, consulting for Diagnostica Stago, serving on an advisory board for Janssen Pharmaceuticals and owning stock in CP Diagnostics.