Early administration of high-dose IV unfractionated heparin blunts sVCAM-1 and improves functional outcome more effectively than 300 mg oral aspirin in acute ischemic stroke.
Methods:We studied prospectively 167 patients with ischemic stroke (58% males, 67.7± 9.8 years) that received 1000 IU/h i.v. unfractionated heparin (UFH) (n=70) or 300 mg oral aspirin (n=97) at a mean treatment delay of 6.7 hours (95% CI 5.9–7.4). Baseline and 48 hours plasma levels of IL-6, IL-10, IL-4, TNF-α, sICAM-1, and sVCAM-1 were compared in both treatment groups. All patients had baseline and follow up CT scans, and stroke diagnosis followed TOAST criteria. Multivariate analyses adjusting for confounders assessed the impact of cytokines and adhesion factors on the Barthel Index (BI) score at 6 months. Results: Whereas TNF-α, and sICAM-1 decreased at follow-up, IL-6, IL-4, and sVCAM-1 increased compared to baseline values (all p<0.01). sVCAM-1 levels, adjusted for baseline inflammatory levels, neurological impairment, and CT findings were significantly lower at follow-up in patients treated with UFH (p=0.01). Other inflammatory markers did not differ between aspirin and UFH. Independent predictors of poor outcome (BI < 85) included 5 mm Hg increase in MAP (OR 1.16, 1.01–1.33), early CT signs of infarction (OR 8.30, 2.8–24.64), 1°C increase in body temperature (OR 3.23, 1.58–6.6), 1 point decrease in the Canadian Stroke Scale (OR 1.66, 1.31–2.12), and a twofold increase at 48 hours of baseline sVCAM-1(OR 2.19,1.1–4.39). Conclusions: The rise of sVCAM-1 is an independent predictor of clinical outcome at 6 months in patients with ischemic stroke. sVCAM-1 is more effectively decreased with high-dose UFH than with aspirin. To confirm that shorter heparin delay, IV route, and high-dose are required to blunt inflammation and improve functional outcome more effectively than aspirin in ischemic stroke a multinational trial has been organized, the Rapid Anticoagulation Prevents Ischemic Damage (RAPID) study.