Findings from a small preliminary clinical trial (TEACH; ClinicalTrials.gov identifier: NCT01763606) of 10 patients with cancer and acute ischemic stroke (AIS) suggest that there is no significant benefit for anticoagulation vs antiplatelet therapy on cumulative rates of major bleeding, thromboembolic events, and survival. The results were published in JAMA Neurology.
The investigators conducted a pilot study that compared enoxaparin with aspirin in patients age 18 to 85 with active solid or hematologic cancers and magnetic resonance imaging (MRI)-confirmed AIS within 4 weeks. All patients were randomly assigned to receive subcutaneous enoxaparin 1 mg/kg twice daily or oral aspirin 81 to 325 mg/d for 6 months.
The primary study outcome was feasibility, which was defined as an enrollment rate in 100 eligible patients in whom the lower-bound 95% CI value was >30%. This outcome was based on the prespecified determination that enrolling 40 of 100 eligible participants (ie, 40%; 95% CI, 30.3%-50.3%) would denote feasibility for future larger clinical trials. Feasibility, efficacy, and safety outcomes between the intention-to-treat groups were evaluated using descriptive statistics and Kaplan-Meier survival analyses.
Between January 2013 and April 2016, a total of 469 patients with cancer and suspected AIS were screened. Overall, 10.4% (49 of 469) of patients met eligibility criteria. Clear indications for anticoagulation (30%; n=128) and inactive cancer (20%; n=83) were the main exclusion criteria. The investigators ultimately enrolled 20 of 49 eligible patients (41%; 95% CI, 27%-55%), demonstrating that upon termination the study was on schedule to meet the prespecified feasibility end point of 30% enrollment.
Enrollment failures were due to patient aversion to injections (38%; n=11), patient/physician preference for anticoagulation (31%; n=9), patients declining participation in a clinical trial (24%; n=7), and patient/physician preference for antiplatelet therapy (7%; n=2).
Ultimately, 10 patients were randomly assigned to each of the two treatment arms. Of these, 6 patients (60%) in the enoxaparin arm crossed over to the aspirin arm due to discomfort associated with receiving injections (n=4) or drug costs (n=2). The median time to crossover in the participants was 6 days. At 1-year follow-up, 3 patients randomly assigned to aspirin experienced nonfatal bleeding and 1 patient randomly assigned to enoxaparin experienced a nonfatal pulmonary hemorrhage. In addition, 1 patient randomly assigned to receive aspirin experienced a nonfatal myocardial infarction and 1 patient randomly assigned to receive enoxaparin experienced a fatal recurrent AIS.
The investigators concluded that larger blinded clinical trials designed to determine the ideal antithrombotic strategy to use in this high-risk population are both safe and feasible. Therefore, comparisons of aspirin with direct oral anticoagulants rather than injectables should be considered in future clinical trials.
Navi BB, Marshall RS, Bobrow D, et al. Enoxaparin vs aspirin in patients with cancer and ischemic stroke: the TEACH pilot randomized clinical trial [published online January 8, 2018]. JAMA Neurol. doi:10.1001/jamaneurol.2017.4211