The TARGET trial: hit or miss?

Over the past 8 years large-scale, placebo-controlled trials have established the efficacy of intravenous platelet glycoprotein (GP) IIb/IIIa inhibitors at reducing the 30-day composite of death, myocardial infarction, and urgent target vessel revascularization associated with percutaneous coronary angioplasty, atherectomy, and stent placement. Using abciximab, tirofiban, or eptifibatide, each trial showed a pattern of benefit suggesting an element of class effect, however, the relative risk reductions among these studies ranged from 24% to 55%. While it was generally held that percutaneous coronary intervention trials using the monoclonal antibody, abciximab, demonstrated a more consistent and numerically greater benefit than those with small-molecule agents, no direct comparison of trials could be fairly made. Thus, it was uncertain if variability in trial outcomes were related to differences in the study populations, the protocols, or the particular IIb/IIIa inhibitor utilized. A necessary next step for the field was a head-tohead trial of GP IIb/IIIa inhibitors, using abciximab as the comparator and the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trial as the study model. Specifically, inclusion criteria, endpoint definitions, and sample size calculations were based upon EPISTENT. The Do Tirofiban and ReoPro Give Similar Efficacy Outcome Trial (TARGET) was designed to test whether tirofiban was not inferior to abciximab among percutaneous coronary intervention–stent patients. Unique to TARGET (as compared with EPISTENT) were third generation coronary stents, vascular access closure devices, and an emphasis on pre-procedural clopidogrel. These features made the study as real-world as possible and facilitated an enrolment of 4809 patients in under 8 months. At 30 days the primary efficacy end-point of death, myocardial infarction, and urgent target vessel revascularization occurred more frequently among the tirofiban-treated group (hazard ratio 1·26; 95% CI 1·01–1·57; P=0·038). Major bleeding rates were similar between the two study groups, though minor bleeding and thrombocytopenia occurred more often among abciximab-treated patients. The overall results of TARGET are themselves worthy of consideration. Since this trial is one of the largest percutaneous coronary intervention–stent studies ever performed, involves 149 medical centres