Stroke Alert: A Review of Current Clinical Stroke Literature

By Matthew E. Fink, MD, Interim Chair and Neurologist-in-Chief, Department of Neurology and Neuroscience, Weill Cornell Medical College

Potent Antiplatelet Medication Causes Excessive Intracranial Bleeding

Source: Morrow DA, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 2012;366:1404-1413. DOI: 10.1056/NEJMoa1200933.

Vorapaxar is a potent antiplatelet medication with a novel action that works by inhibiting thrombin activation of platelets through the protease-activated receptor PAR-1. In an international trial of 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease, vorapaxar 2.5 mg daily or placebo was randomly administered and patients were followed for a median of 30 months. The primary endpoint was a composite of death from cardiovascular causes, myocardial infarction, or stroke. However, after 2 years of enrollment, the safety monitoring board recommended termination of the study because of an excess of intracranial hemorrhage in the treated group, compared to placebo.

After 3 years of follow-up, the primary endpoint occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio [HR] = 0.87; 95% confidence interval [CI] 0.80-0.94; P < 0.001). Moderate-to-severe bleeding occurred in 4.2% of patients treated with vorapaxar and 2.5% of those who received placebo (HR = 1.66; 95% CI, 1.43-1.94; P < 0.001) with an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0% vs 0.5%; P < 0.001). Although vorapaxar reduced the risk of secondary cardiovascular death and ischemic events, there was an increased risk of serious bleeding complications, including intracranial hemorrhage.

Bridging Therapy with Thrombolysis Appears to Be Safe and Effective

Source: Mazighi M, et. al. Bridging therapy in acute ischemic stroke. A systematic review and meta-analysis. Stroke 2012;43:1302-1308.

There are no definitive, randomized, controlled clinical trials that have been reported regarding intravenous to intra-arterial bridging therapies with thrombolytics in patients with acute ischemic stroke. The investigators performed a meta-analysis of 15 studies and used pooled data to determine if this therapy was effective and safe.

The pooled estimate for recanalization was 69.6% (95% CI, 63.9-75.0). Pooled estimates of clinical outcomes were 48.9% for favorable outcome, 17.9% for mortality, and 8.6% for symptomatic intracranial hemorrhage. In a meta-regression analysis, the shorter the mean time to intravenous treatment, the greater the recanalization rate and the lower the mortality. By comparing bridging therapy with published results of intravenous alteplase alone, bridging therapy was associated with a favorable outcome (OR = 2.26) with no difference in mortality or symptomatic intracranial hemorrhage. Time to intravenous treatment remains the most important determinant of outcome.

Elderly Women with Atrial Fibrillation Have a Greater Risk of Stroke Than Men

Source: Avgil Tsadok M, et al. Sex differences in stroke risk among older patients with recently diagnosed atrial fibrillation. JAMA 2012;307:1952-1958.

The reasons for the higher risk of stroke in women who have atrial fibrillation (AF), compared to men, is unclear, but under-treatment with warfarin has been suggested as a cause. In a population-based cohort study of patients 65 years or older admitted to the hospital with recently diagnosed AF in Quebec, Canada, from 1998-2007, administrative data were used to link hospital discharge diagnoses with warfarin use. The cohort comprised 39,398 men (47.2%) and 44,115 women (52.8%). On admission, women were older and had a higher CHADS score. At 30 days post-discharge from the hospital, 58.2% of men and 60.6% of women had filled a prescription for warfarin. Adherence to warfarin treatment was good in both male and female groups. Crude stroke incidence was 2.02 per 100 person-years in women (95% CI, 1.95-2.10) vs 1.61 per 100 person-years in men (95% CI, 1.54-1.69, P < 0.001) and was driven by the population of patients 75 years or older.

In a multivariate Cox regression analysis, women had a higher risk of stroke than men (HR = 1.14, 95% CI = 1.07-1.22, P < 0.001) after adjusting for comorbid conditions, individual components of the CHADS score, and warfarin treatment. The risk of stroke was higher in elderly women, compared to men, regardless of warfarin use, but the causes remain undetermined.