Routine upstream versus selective downstream administration of glycoprotein IIb/IIIa inhibitors in patients with non-ST-elevation acute coronary syndromes: A meta-analysis of randomized trials

Background: Glycoprotein (GP) IIb/IIIa inhibitors reduce ischemic complications in patients with non-ST-elevation acute coronary syndromes (NSTEACS) who undergo invasive procedures. However the optimal timing of therapy (upstream - at hospital admission in all patients prior to coronary catheterization, or downstream - after coronary angiography selectively in patients prior to percutaneous coronary intervention) is still debated. The aim of this meta-analysis was to compare the outcome of NSTEACS patients randomized to routine upstream versus deferred selective downstream GP IIb/IIIa inhibitors. Methods: We scanned the literature from January 1990 to May 2009 to identify all randomized trials comparing upstream administration of GP IIb/IIIa inhibitors versus its downstream use in invasively managed NSTEACS. Results: In 5 randomized trials a total of 9753 patients were randomized to upstream GP IIb/IIIa inhibitors therapy versus 9716 patients randomized to deferred selective downstream therapy. Upstream therapy was associated with reduced in-hospital or 30-day major adverse ischemic cardiac events (odds ratio = 0.90 [95% confidence interval 0.82-0.98], p = 0.02). However the risk of major bleeding was significantly higher with upstream therapy (odds ratio = 1.35 [1.11-1.63], p = 0.002). Combining ischemic and hemorrhagic events in a net clinical end-point showed no significant differences between the two approaches (odds ratio = 1.01 [0.92-1.10], p = 0.88). Conclusions: In conclusion early administration of GP IIb/IIIa inhibitors in NSTEACS is associated with significant reduction in ischemic events compared to a selective deferred therapy after coronary angiography. However upstream therapy is also associated with increased bleeding complications. This approach should therefore be reserved for patients at high ischemic and/or low hemorrhagic risk.