MD Conference Express ISC 2012 - (Page 12)
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However, the difference in ischemic stroke was significant, with the per-year death rate in the warfarin group (n=23) of 0.72% compared with 1.36% in the aspirin group (n=55; p=0.005). The main secondary outcome occurred at a rate of 12.7% per year in warfarin-treated patients versus 12.15% per year in the aspirin-treated group (p=0.33). Major hemorrhage per year, however, occurred in 1.78% of patients in the warfarin group versus 0.87% in patients who were taking aspirin (p<0.001). Significant differences were observed in gastrointestinal hemorrhage (p=0.01) and “all other bleeds” (p=0.01). Importantly, no difference in intracerebral or intracranial bleeding was found; combined, the annual rates were 0.27% in the warfarin group compared with 0.22% in the aspirin group (p=0.82). The authors concluded that there was no overall difference for the primary outcome, although there was a suggestive benefit with warfarin at 4 years and beyond. Warfarin reduced ischemic stroke risk throughout followup, but patients who were on the drug had more major hemorrhages than those in the aspirin group (1.78% vs 0.87%). Intracerebral and intracranial outcomes were similar. No significant difference was observed for the main secondary outcome. Given no overall benefit of warfarin and increased risk of bleeding, the study found no compelling evidence to use warfarin for all patients. Based on effectiveness in preventing stroke and the possible benefit of warfarin after 4 years, analyses are underway to better identify patients that will benefit from warfarin or aspirin.
AXIS 2 was a randomized, double-blind, placebocontrolled, two-arm, multinational, multicenter trial that included 328 patients with acute ischemic stroke in the middle cerebral artery territory. The objective was to demonstrate the efficacy of AX200 (rhG-CSF; filgrastim) versus placebo. The most relevant inclusion criteria were that patients had to be <9 hours from symptom onset, have a National Institute of Health Stroke Scale (NIHSS) of 6 to 22, have a diffusion-weighted imaging lesion >15 cm3, and be aged ≤85 years. Recombinant tissue plasminogen activator (rtPA) was allowed if patients were still eligible after lysis (ie, had an NIHSS of at least 6). Patients were randomized to receive 135 µg/kg of AX200 over 72 hours intravenously or placebo, with one-third given over 30 minutes as a priming dose. The primary endpoint was modified Rankin scale (mRS) score at Day 90. The secondary endpoint was NIHSS at Day 90. Additional analyses were performed on infarct growth, adverse events, mortality, cytokines, and hematology. The study was conducted at 51 sites in 7 countries. Intention-to-treat (ITT; n=323) and per-protocol analyses (n=272) were performed. Patients had a mean age of 63±10 years, and there were no significant differences in demographics. Hematology tests showed an expected increase in white blood cells and monocytes and a small decrease in platelets. No significant differences were observed in serious adverse events. There were no significant differences between AX200 and placebo patients in the primary efficacy endpoint (mRS at Day 90) in either the ITT or per-protocol groups, and there was broad overlap in confidence intervals (Figure 1). The same outcome was seen in the secondary endpoint (NIHSS at Day 90; Figure 2). No significant differences between the AX200 and control groups were observed in the subgroup analysis for rtPA pretreatment, either. Figure 1. mRS Day 90 AXIS200 Efficacy Endpoint.
Treatment AX200 Placebo Relative Change p value FAS (ITT Analysis) Mean mRS (+CI) 3.31 (3.06 to 3.56) 3.12 (2.87 to 3.37) 0.19 (-0.17 to -0.55) 0.3034
AXIS 2 Clinical Outcomes No Different Than Placebo
Written by Rita Buckley
AX200 was a novel and promising drug candidate with a comprehensive preclinical and clinical package that fulfilled Stroke Therapy Academic Industry Roundtable (STAIR) and European Stroke Organization recommendations; yet, no difference was observed in clinical outcome or imaging compared with placebo in acute ischemic stroke patients, according to results from the AX200 for the Treatment of Ischemic Stroke Phase 3 trial [AXIS-2; NCT00927836]. E. Bernd Ringelstein, MD, Westfälische Wilhelms Universität Münster, Münster, Germany, reported outcomes from the study.
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Treatment AX200 Placebo Relative Change p value
PPS (Per Protocol) Mean mRS (+CI) 3.26 (2.98 to 3.53) 3.06 (2.79 to 3.33) 0.20 (-0.19 to -0.59) 0.3093
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Adjusted for the pre-specified baseline characteristics age, NIHSS, infarct volume.
Reproduced with permission from EB Ringelstein, MD.
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April 2012
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Table of Contents for the Digital Edition of MD Conference Express ISC 2012
MD Conference Express ISC 2012
From Neurovascular Laboratory to Clinic: A Journey Through Time
No Compelling Evidence to Use Warfarin or Aspirin in Heart Failure Patients
AXIS 2 Clinical Outcomes No Different Than Placebo
SAMMPRIS: 30-Day Outcomes After Angioplasty and Stenting
Aggressive Medical Therapy Benefits Those Who Fail Antithrombotic Therapy
Initial Clinical Results with TREVO® Mechanical Thrombectomy Device are Promising
Linking sICH Definitions to Outcomes
Solitaire™ Flow Restoration Device Achieves Successful Recanalization Free of Symptomatic Hemorrhage Transformation
FIA II Seeks Genetic Underpinnings of Familial Intracranial Aneurysm
SPS3 Study Does Not Support the Use of Combination Therapy for Stroke Prevention
Novel Agent NA-1 Proves that Ischemic Neuroprotection is Possible in Older Patients
Acute Endovascular Treatment
Neuroimaging
Stroke Guidelines: Current Recommendations in Principle and Practice
The Rising Trend of Ischemic Stroke in the Young
Advanced Neuroimaging Adds Time, Reduces Endovascular Treatment in Clinical Practice
MD Conference Express ISC 2012
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