Dabigatran as effective as warfarin to prevent VTE recurrence

April 15, 2013

Data from the RE-MEDY trial suggest that Pradaxa is as effective as warfarin for long-term, extended antithrombotic therapy in patients who have already received at least three months of anticoagulation for VTE

Anticoagulation Therapies

Data from the RE-MEDY trial suggest that dabigatran etexilate (Pradaxa) is as effective as warfarin for long-term, extended antithrombotic therapy in patients who have already received at least three months of anticoagulation for venous thromboembolism (VTE).

RE-MEDY randomized 1,430 patients to dabigatran and 1,426 to warfarin. Over a follow-up of six to 36 months, dabigatran's hazard ratio (HR) for the primary end point of recurrent or fatal VTE, compared with that of warfarin, was 1.44 (95% CI 0.78-2.64, P=0.01 for noninferiority). Major or clinically relevant bleeding was significantly reduced in the dabigatran group, with HR 0.54 (95% CI 0.41-0.71, P<0.001).

Of note, there were significantly more cases of acute coronary syndrome (ACS) in the dabigatran group (0.9%) vs 0.2% for those who took warfarin (P=0.02). This finding is similar to what was observed in the RE-LY trial, one of the pivotal approval trials for dabigatran. In that study, there was an increased risk of myocardial infarction in patients treated with dabigatran compared with warfarin.

Source: Schulman S, Kearon C, Kakkar AK, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013; 368:709–718. http://www.nejm.org/doi/full/10.1056/NEJMoa1113697.

Clopidogrel plus aspirin shows benefit after TIA

New data presented at the International Stroke Conference suggest that a short course of aspirin plus clopidogrel begun immediately after a transient ischemic attack (TIA) or minor stroke outperforms aspirin alone in decreasing the risk of a subsequent stroke.  

The Chinese trial enrolled 5,170 patients of at least 40 years of age who had suffered a TIA or minor stroke. Within 24 hours of their symptom onset, they were randomized to one of two groups: aspirin (75-300 mg one-day loading dose followed by 75 mg/day) plus placebo, or the same aspirin regimen plus clopidogrel (loading dose of 300 mg followed by 75 mg/day). Aspirin was discontinued after 21 days in the combination group.

The study showed that stroke occurred less frequently in those receiving both aspirin and clopidogrel. At 90 days, the HR for stroke-free survival in the combination group was 0.68 (95% CI 0.57-0.81; P<0.001). For the secondary outcome of combined events (stroke, MI, vascular death), the HR was 0.69 (95% CI 0.58-0.82; P<0.001). The risk of hemorrhagic stroke was the same in the two groups (0.3%). Rates of major bleeding were similar between both groups and very low (0.2%).

Source: Anderson P. Short course of aspirin, clopidogrel cuts stroke risk [press release]. Honolulu, Hawaii.  February 12, 2013. http://www.theheart.org/article/1505279.do. Accessed March 2, 2013.

Primary VTE prophylaxis in ambulatory cancer patients

Malignancy is a major risk factor for the development of VTE in the surgical, medically ill, and ambulatory populations. Because of this, VTE prophylaxis is an important consideration. A recently published review of the literature examining the efficacy and safety of VTE prophylaxis in ambulatory cancer patients suggests that the risks may differ, depending on type and stage of malignancy.

The review included 14 studies, all of which were randomized trials. The authors found that strong evidence for primary prophylaxis exists for several populations with advanced or metastatic cancer considered to be at high risk, including those with pancreatic cancer, lung cancer, or multiple myeloma. Evidence was inconsistent or lacking for lower-risk cancer populations, such as those with breast cancer, or for those with malignant glioma. Glioma carries a high risk for VTE and an increased risk for bleeding relative to the general ambulatory cancer population.

Use of antithrombotic agents has reduced the rate of primary VTE, with minimal increases in bleeding risk in specific ambulatory cancer populations. However, further investigation is needed to guide recommendations for primary VTE prophylaxis.

Source: Aikens GB, Rivey MP, Hansen CJ. Primary venous thromboembolism prophylaxis in ambulatory cancer patients. Ann Pharmacother. 2013; 47:198–209. http://www.theannals.com/content/47/2/198.abstract.