The dark side of platelet glycoprotein IIb/IIIa receptor inhibitors during percutaneous coronary interventions.

Numerous placebo-controlled randomized clinical trials have demonstrated the benefit of intravenous glycoprotein (GP) IIb/IIIa inhibitors in percutaneous coronary interventions (PCIs). These agents decrease the incidence of adverse events associated with PCI in various clinical settings (ST-elevation myocardial infarction, acute coronary syndromes, and elective PCI). However, great controversy remains as to whether this benefit is confined to the prevention of small periprocedural myocardial infarctions, because a longer term clinical advantage has not been definitively shown, except with myocardial infarctions comprised of very large (3 to 5 times normal) enzymatic increases. Nevertheless, all existing clinical trials demonstrate either a small but statistically significant benefit or a trend favoring their use. Meta-analytic methods show that although the degree of the benefit is small, when viewed in the aggregate, it appears convincing. These conclusions pertain to all 3 commercially available agents, although specific indications for use as adjuncts in PCI in particular clinical scenarios are suggested by the clinical data and Food and Drug Administration labeling. Although this class of agents is defined by their main action— blocking the platelet GP IIb/IIIa receptor—the different inhibitors vary with respect to duration of action at the target receptor, specific receptor affinity, and binding sites. In the study published in the April 15th issue of the American Journal of Cardiology , Vakili and colleagues1 presented data from the New York State Registry collected in 1997 and 1998. The results suggested that GP IIb/IIIa inhibitors may actually lead to increased major adverse events (7.8% vs 3.8%, p 0.006) and stent thrombosis (0.9% vs 0.5%, p 0.008). The main types of adverse events experienced were periprocedural increases in enzymes, many at 3 to 5 times the upper limit of normal (9.5% vs 14.5%, p 0.001), and periprocedural myocardial infarctions (3.1% vs 6.5%, p 0.001). This startling conclusion, which conflicts with all previous trial data, warrants serious reflection, and should stimulate a lively discussion. The New York State PCI Database Registry is a highly respected entity that has provided valuable information in the past. This study therefore cannot be simply shrugged aside, especially as it incorporates data from nearly 11,000 PCI procedures at 5 hospitals. The main criticism of this study, of course, will be that it was not a randomized trial, so when comparing registry results giving 1 conclusion versus several trials showing the opposite, the study design is key. Vakili and colleages 1 used propensity scores to adjust for GP IIb/IIIa inhibitor use and other interactions, and demonstrated a 57% increase in the rate of adverse events solely attributable to GP IIb/IIIa inhibitors. The question raised by this study is whether GP IIb/IIIa inhibitors may have a negative impact on PCI outcomes. Although clinical trials are the definitive method to answer most clinical questions, the details of study design may subtly affect the results. 2‐ 4 Clinical trials of new drugs are funded and designed primarily to bring a commercial product to market. It is quite appropriate for a pharmaceutical company to wish to make a profit—that is their business. Additionally, it is a moral imperative for physicians to participate in