Platelet glycoprotein IIb/IIIa blockers during percutaneous coronary intervention and as the initial treatment of acute coronary syndromes

During the last two decades, doctors have been looking for the best treatment to prevent clots in the coronary arteries of patients with coronary heart disease. This review summarises the results of 60 studies which used a potent class of intravenous antiplatelet drugs - glycoprotein IIb-IIIa blockers - in 66,689 participants. This treatment was tested in two different conditions: in patients undergoing coronary angioplasty (inserting a deflated small balloon in the artery and expand it to open the vessel) with or without inserting a stent (a thin metal expandable tube or sleeve to scaffold the artery open); and as the initial treatment of patients hospitalised for unstable angina and non-ST segment elevation acute myocardial infarction (prolonged coronary chest pain with or without small myocardial infarction). The evidence is up to date as January 2013 and the overall quality of the body of evidence was good.

Overall, the use of these drugs during coronary angioplasty with or without inserting a stent reduced the risk of death at 30 days, and the risk of death or myocardial infarction at 30 days and at six months. The results were similar for stable and for unstable patients with coronary artery disease, but there was comparatively less benefit for patients previously treated with clopidogrel, an oral antiplatelet drug. On the other side, these drugs only slightly reduced the risk of death or myocardial infarction when administered as initial medical treatment in patients with unstable angina or non-ST-elevation myocardial infarction. The benefits of glycoprotein IIb/IIIa blockers need to be balanced against the increased risk of bleeding.

Authors' conclusions: 

When administered during PCI, intravenous glycoprotein IIb/IIIa blockers reduce the risk of all-cause death at 30 days but not at six months, and reduce the risk of death or myocardial infarction at 30 days and at six months, at a price of an increase in the risk of severe bleeding. The efficacy effects are homogeneous but are less marked in patients pre-treated with clopidogrel where they seem to be effective only in patients with acute coronary syndromes. When administered as initial medical treatment in patients with NSTEACS, these agents do not reduce mortality although they slightly reduce the risk of death or myocardial infarction.

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Background: 

During percutaneous coronary intervention (PCI), and in non-ST segment elevation acute coronary syndromes (NSTEACS), the risk of acute vessel occlusion by thrombosis is high. Glycoprotein IIb/IIIa blockers strongly inhibit platelet aggregation and may prevent mortality and myocardial infarction. This is an update of a Cochrane review first published in 2001, and previously updated in 2007 and 2010.

Objectives: 

To assess the efficacy and safety effects of glycoprotein IIb/IIIa blockers when administered during PCI, and as initial medical treatment in patients with NSTEACS.

Search strategy: 

We updated the searches of the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 12, 2012), MEDLINE (OVID, 1946 to January Week 1 2013) and EMBASE (OVID, 1947 to Week 1 2013) on 11 January 2013.

Selection criteria: 

Randomised controlled trials comparing intravenous IIb/IIIa blockers with placebo or usual care.

Data collection and analysis: 

Two authors independently selected studies for inclusion, assessed trial quality and extracted data. We collected major bleeding as adverse effect information from the trials. We used odds ratios (OR) and 95% confidence intervals (CI) for effect measures.

Main results: 

Sixty trials involving 66,689 patients were included. During PCI (48 trials with 33,513 participants) glycoprotein IIb/IIIa blockers decreased all-cause mortality at 30 days (OR 0.79, 95% CI 0.64 to 0.97) but not at six months (OR 0.90, 95% CI 0.77 to 1.05). All-cause death or myocardial infarction was decreased both at 30 days (OR 0.66, 95% CI 0.60 to 0.72) and at six months (OR 0.75, 95% CI 0.64 to 0.86), although severe bleeding was increased (OR 1.39, 95% CI 1.21 to 1.61; absolute risk increase (ARI) 8.0 per 1000). The efficacy results were homogeneous for every endpoint according to the clinical condition of the patients, but were less marked for patients pre-treated with clopidogrel, especially in patients without acute coronary syndromes.

As initial medical treatment of NSTEACS (12 trials with 33,176 participants), IIb/IIIa blockers did not decrease mortality at 30 days (OR 0.90, 95% CI 0.79 to 1.02) or at six months (OR 1.00, 95% CI 0.87 to 1.15), but slightly decreased death or myocardial infarction at 30 days (OR 0.91, 95% CI 0.85 to 0.98) and at six months (OR 0.88, 95% CI 0.81 to 0.96), although severe bleeding was increased (OR 1.29, 95% CI 1.14 to 1.45; ARI 1.4 per 1000).

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