Glycoprotein IIb-IIIa Inhibitors for Acute Ischemic Stroke
- acute stroke
- antiplatelet agents
- antiplatelet drugs
- brain infarction
- brain ischemia
- cerebral infarct
- cerebrovascular accident
- platelet inhibitors
- randomized controlled trials
- stroke management
- glycoprotein IIb-IIIa inhibitors
- systematic review
Section Editor: Graeme J. Hankey MD, FRCP
Glycoprotein (GP) IIb-IIIa inhibitors block the final common pathway to platelet aggregation antagonizing with receptors that bind fibrinogen molecules forming bridges between adjacent platelets. Thus, GP IIb-IIIa inhibitors could favor endogenous thrombolysis by reducing thrombus growth and prevent thrombus reformation by competitive inhibition with fibrinogen. Currently used in clinical practice for acute coronary syndromes and percutaneous coronary interventions, they could be useful also for patients with acute ischemic stroke.
To perform a systematic review of controlled clinical trials in order to assemble all the available data to evaluate the potential efficacy and safety of GP IIb-IIIa inhibitors in patients with acute ischemic stroke.
We searched the Cochrane Stroke Group Trials Register (last searched May 31, 2005). In addition we searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library, 2005 Issue 2), MEDLINE (1966 to June 2005) and EMBASE (1980 to June 2005). In an effort to identify further published, unpublished and ongoing trials we searched reference lists and contacted authors and pharmaceutical companies.
We aimed to analyze unconfounded randomized controlled trials comparing GP IIb-IIIa inhibitors with placebo in patients with acute ischemic stroke. Only patients who started the treatment within 6 hours of stroke onset were included.
Data Collection and Analysis
Three reviewers independently selected trials for inclusion, assessed trial quality and extracted the data.
Two trials involving 474 patients were included. Only data on 414 patients treated within 6 hours were considered. Patients were treated with intravenous abciximab or placebo. Treatment with abciximab was associated with a nonsignificant reduction of death and dependency combined (OR 0.79; 95% CI, 0.54 to 1.17; Figure) and of death alone (OR 0.67; 95% CI, 0.36 to 1.25). Treatment with abciximab was associated with a nonsignificant increase of symptomatic intracranial hemorrhages (OR 4.13; 95% CI, 0.86 to 19.67) and of major extracranial hemorrhages (OR 1.51; 95% CI, 0.25 to 9.12).
During the preparation of this review, Abciximab in Emergent Stroke Treatment Trial-II (AbESTT-II) stopped recruitment after 808 patients of the 1800 planned had been included, because of an excess of ICH in the treatment group, and an unfavorable risk benefit ratio. These data will be available only with the publication of the full results of the trial. The Safety of Tirofiban in Acute Ischemic Stroke (SaTIS) trial of a different GP IIb-IIIa inhibitor, tirofiban, in 240 patients has also recently been completed and presented, and suggests the agent is safe. A further trial of this agent (SETIS: Study of Efficacy of Tirofiban in acute Ischemic Stroke) is ongoing. As soon as AbESTT-II and SaTIS studies have been published in full, this review will be updated, though clearly the results of the much larger AbESTT-II will predominate.
There is currently not enough evidence from randomized controlled trials regarding the efficacy or safety of GP IIb-IIIa inhibitors therapy in acute ischemic stroke.
The question of whether GP IIb-IIIa inhibitor does more good than harm for acute ischemic stroke will be probably answered soon after the publication of AbESTT-II, SaTIS and SETIS studies. Taking into account the recent and premature interruption of the AbESTT-II trial attributable to high rate of ICH, it seems crucial to see whether the early risk of ICH is offset by a benefit on long-term death and disability.
Note: The full text of this review is available in the Cochrane Library (for subscribers: www.update-software. com/Cochrane). The full article should be cited as: Ciccone A, Abraha I, Santilli I. Glycoprotein IIb-IIIa inhibitors for acute ischemic stroke (Cochrane Review). In: The Cochrane Library, Issue 4, 2006. Oxford: Update Software. © Cochrane Library, John Wiley & Sons Ltd.
- Received September 27, 2006.
- Accepted October 2, 2006.