Dabigatran vs. warfarin in patients with mechanical heart valves

Patients with mechanical heart valves are at high risk for thrombotic events and require life-long treatment with anticoagulation. Warfarin has historically been the drug of choice for these patients, but the development of target-specific anticoagulants has raised the question of possible use in this population.

A recent phase 2 dose-validation study included two populations of patients: those who had undergone aortic- or mitral-valve replacement within the past seven days and those who had undergone such replacement at least three months earlier.

Patients were randomly assigned in a 2:1 ratio to receive either dabigatran or warfarin. Selection of the initial dabigatran dose (150, 220, or 300 mg twice daily) was based on kidney function. Doses were adjusted to obtain a trough plasma level of at least 50 ng/mL. The warfarin dose was adjusted to obtain an international normalized ratio of 2-3 or 2.5-3.5 on the basis of thromboembolic risk. The primary end point was the trough plasma level of dabigatran.

The trial was terminated prematurely after the enrollment of 252 patients because of an excess of thromboembolic and bleeding events among patients in the dabigatran group. In the as-treated analysis, either dose adjustment or discontinuation of dabigatran was required in 52 of 162 patients (32%). Ischemic or unspecified stroke occurred in 9 patients (5%) in the dabigatran group and in no patients in the warfarin group. Major bleeding (all of which was pericardial) occurred in seven patients (4%) and two patients (2%), respectively.

Source: Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369:1206-1214.

ASCO updates recommendations for VTE prophylaxis and treatment in patients with cancer

A 2013 update by the American Society of Clinical Oncologists adds two new recommendations for VTE prophylaxis and cancer. The first focuses on communication between the patient and provider, and stresses that all patients with cancer be educated about the risks of VTE and given clear information regarding the signs and symptoms of VTE. Two recent patient surveys found that fewer than 50% of patients are aware that malignancy carries increased risk of VTE.

The other new recommendation is that patients with cancer be assessed for VTE risk at the time of chemotherapy initiation and periodically thereafter.

Slight changes were made to the remaining recommendations after the panel considered all evidence published since the guidelines were issued in 2007. Routine use of thromboprophylaxis is still not recommended for ambulatory patients, despite trials that have shown benefit, because it is not cost-effective. The exception to this is for multiple myeloma patients who are receiving thalidomide or lenalidomide along with chemotherapy and/or dexamethasone.

Source: Lyman GH, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. JClin Oncol. 2013:2189-2204.

Major dabigatran bleeding events require less intensive management

A recently published comparison of the management and prognosis of patients with major bleeding events on warfarin or dabigatran concluded that patients treated with dabigatran required less intensive management.

Two independent investigators reviewed bleeding reports from 1,034 individuals with 1,121 major bleeds. Patients with major bleeds on dabigatran were older, had lower creatinine clearance, and more frequently used aspirin or nonsteroidal anti-inflammatory agents than did those on warfarin.

The 30-day mortality after the first major bleed tended to be lower in the dabigatran group (9.1%) than in the warfarin group (13.0%). Major bleeds in dabigatran patients were more frequently treated with blood transfusions (61%) than bleeds in warfarin patients (42%) but less frequently with plasma (dabigatran, 19.8%; warfarin, 30.2%). Patients who experienced a bleed had shorter stays in the intensive care unit if they had previously received dabigatran (mean 1.6 nights) compared with those who had received warfarin (mean 2.7 nights).

Source: Majeed A, Hwang H, Connolly SJ, et al. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation. 2013;CIRCULATIONAHA.113.002332; published online before print, September 30, 2013.