Abstract
In the EINSTEIN PE study rivaroxaban (RX) was found to be as effective as warfarin in the treatment of acute pulmonary embolism (PE) with superior safety. However, study results need to be confirmed in unselected PE patients in daily care.
Using prospectively collected data from a large regional registry of patients treated with novel direct oral anticoagulants (NOAC) in the district of Saxony, Germany, we evaluated the rate of recurrent VTE, other cardiovascular complications and bleeding events in patients receiving rivaroxaban for acute PE. In this ongoing registry, a network of 239 physicians enrols up to 2500 daily care NOAC patients who receive central prospective follow up (FU) by the registry office at day 30 day and quarterly thereafter to collect efficacy and safety data. All outcome events are centrally adjudicated using standard scientific definitions.
Until July 31th 2013, 2249 patients were enrolled. Of these, 72 patients received RX for acute PE treatment (demographic data in table 1). Registry patients were older than the EINSTEIN PE population (67.3 vs. 55.8 years), 55.6% were female and 23.6% were treated for a recurrent VTE. During follow-up, unplanned rivaroxaban discontinuation rates were low (around 5%; table 1). So far, only one recurrent VTE event occurred (1.7 events per 100 patient years). One patient experienced non-fatal ischaemic stroke within 4 weeks after PE diagnosis (1.7 events per 100 patient years). Bleeding complications were frequent but only 2 major bleeding (non-fatal vaginal bleeds) occurred (3.3 events per 100 patient years). During follow-up three patients died of underlying diseases but none of these deaths were related to VTE or bleeding complications.
Efficacy and safety outcomes at 1, 3, 6 and 12 months follow-up (FU) of rivaroxaban therapy after acute PE (events listed in each FU occurred after previous FU).
| 1-month-FU n (%) | 3-month-FU n (%) | 6-month-FU n (%) | 12-month-FU n (%) | Total events n (%) | Events per 100 patient years | |
|---|---|---|---|---|---|---|
| FU completed | 72 | 67 | 55 | 19 | NA | NA |
| Rivaroxaban discontinuation | 1 (1.4) | 4 (6.0) | 11 (20.0) | 4 (11.1) | ||
| - unplanned switch to other anticoagulation | 1 (1.4) | 1 (1.5) | 2 (3.6) | 3 (15.8) | ||
| - unplanned complete discontinuation | 0 | 1 (1.5) | 1 (1.8) | 1 (5.3) | ||
| - planned discontinuation (end of treatment) | 0 | 2 (3.0) | 8 (14.5) | 0 | ||
| Recurrent VTE | 0 | 1 DVT (1.5) | 0 | 0 | 1 | 1.7 |
| Major cardiovascular events (stroke, ACS, acute limb ischemia, CV death) | 1 stroke (1.4) | 0 | 0 | 0 | 1 | 1.7 |
| Death | 1 (1.4) [no VTE] | 2 (3.0) [no VTE] | 0 | 0 | 3 | 5.0 |
| Any bleeding | 17(23.6) | 11 (16.4) | 0 | 0 | 28 | 46.7 |
| - Minor bleeding | 12 (16.7) | 9 (13.4) | 0 | 2 (10.5) | 23 | 38.3 |
| - NMCR bleeding | 3 (4.2) | 2 (3.0) | 1 (1.8) | 0 | 6 | 10.0 |
| - Major bleeding | 2 (2.8) [both non-fatal] | 0 | 0 | 0 | 2 | 3.3 |
| 1-month-FU n (%) | 3-month-FU n (%) | 6-month-FU n (%) | 12-month-FU n (%) | Total events n (%) | Events per 100 patient years | |
|---|---|---|---|---|---|---|
| FU completed | 72 | 67 | 55 | 19 | NA | NA |
| Rivaroxaban discontinuation | 1 (1.4) | 4 (6.0) | 11 (20.0) | 4 (11.1) | ||
| - unplanned switch to other anticoagulation | 1 (1.4) | 1 (1.5) | 2 (3.6) | 3 (15.8) | ||
| - unplanned complete discontinuation | 0 | 1 (1.5) | 1 (1.8) | 1 (5.3) | ||
| - planned discontinuation (end of treatment) | 0 | 2 (3.0) | 8 (14.5) | 0 | ||
| Recurrent VTE | 0 | 1 DVT (1.5) | 0 | 0 | 1 | 1.7 |
| Major cardiovascular events (stroke, ACS, acute limb ischemia, CV death) | 1 stroke (1.4) | 0 | 0 | 0 | 1 | 1.7 |
| Death | 1 (1.4) [no VTE] | 2 (3.0) [no VTE] | 0 | 0 | 3 | 5.0 |
| Any bleeding | 17(23.6) | 11 (16.4) | 0 | 0 | 28 | 46.7 |
| - Minor bleeding | 12 (16.7) | 9 (13.4) | 0 | 2 (10.5) | 23 | 38.3 |
| - NMCR bleeding | 3 (4.2) | 2 (3.0) | 1 (1.8) | 0 | 6 | 10.0 |
| - Major bleeding | 2 (2.8) [both non-fatal] | 0 | 0 | 0 | 2 | 3.3 |
CV = cardiovascular; VTE = venous thromboembolism; ACS = acute coronary syndrome; NMCR = non-major clinically relevant; NA = not applicable
Acute PE treatment with rivaroxaban in daily care is effective, safe and well tolerated with low rates of unplanned treatment discontinuation. Thromboembolic and major bleeding complications are rare and seem to occur predominantly in the early phase of PE treatment.
At ASH, updated results from our registry will be presented
Werth:Bayer Healthcare: Honoraria. Beyer-Westendorf:Pfizer: Research Funding, Speakers Bureau; Boehringer Ingelheim: Research Funding, Speakers Bureau; Bayer Healthcare: Research Funding, Speakers Bureau.
This icon denotes a clinically relevant abstract
