ESPRIT study design and outcomes--a critical appraisal.
Evidence is needed to guide therapeutic decisions on patients who had ischaemic cerebral events. The recently published European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT), an open-label randomised controlled study, compared long-term treatment of patients randomised to aspirin 30-325 mg daily with (n = 1363) or without (n = 1376) dipyridamole 200 mg twice daily. The study found the combination to be superior to aspirin alone (13% vs. 16% events in a composite endpoint of vascular death, non-fatal stroke, non-fatal myocardial infarction, or major bleeding; hazard ratio 0.8; 95% confidence interval 0.66-0.98). In the interpretation of the results, criticism has been raised related to the study design (open-label, change during the study), the study conduct (half of the aspirin patients underdosed, 33% drop-out rate in the combination group, missing information on potential confounders such as protective concomitant medication), and the outcomes (lack of differences in the efficacy outcomes between the intent-to-treat and the on-treatment populations, lack of differences in minor bleedings between treatment groups, borderline statistical significance of primary study endpoint). Further studies are needed to determine the place of aspirin/dipyridamole combinations in the secondary prevention of stroke.
Einhäupl
Karl
K
Department of Neurology, Medical School, Charité, Berlin, Germany. karl.einhaeupl@charite.de
D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D002545:Brain Ischemia / Q000453:epidemiology / Q000517:prevention & control; D004176:Dipyridamole / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D010352:Patient Dropouts / Q000706:statistics & numerical data; D011446:Prospective Studies; D012107:Research Design; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control*; D016896:Treatment Outcome; D014652:Vascular Diseases / Q000401:mortality
D015415:Biomarkers; D005343:Fibrinolytic Agents; D004176:Dipyridamole; D001241:Aspirin