Platelet glycoprotein inhibitors in patients with medically managed acute coronary syndrome: does the enthusiasm exceed the science?

Guidelines from the American Heart Association and the American College of Cardiology, as well as numerous review articles, have strongly and enthusiastically recommended that platelet glycoprotein IIb/IIIa inhibitors be used in patients with medically managed unstable angina or non-ST-segment myocardial infarction (UA/NSTEMI). We explore whether there is sufficient experimental evidence to justify these recommendations. We review the 4 large randomized trials of US Food and Drug Administration-approved platelet glycoprotein IIb/IIIa inhibitors that included medically managed UA/NSTEMI patients, first taking each trial's results at face value and then in the context of likely biases. The risk differences, unadjusted for potential biases, are 2.5% (0.6%, 4.4%) for the Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) study, 2.3% (-1.9%, 6.5%) for the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) study (tirofiban plus heparin), 0.9% (-0.9%, 2.8%) for the Platelet Glycoprotein IIb/IIIa in Unstable Angina Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, -0.2% (-1.7%, 1.3%) for the least harmful treatment arm of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-IV) trial, and -1.9% (-6.8%, 3.0%) for the PRISM-PLUS study (tirofiban alone) (positive numbers indicate benefit). The 95% confidence interval produced by combining the studies using a random effects model is -1.3% to 3.2% (mean 0.9%); this is consistent with drugs providing a small benefit, no benefit, or causing harm. Confounding caused by the nonrandom selection of patients for percutaneous transluminal coronary angioplasty and coronary artery bypass grafting in all trials except GUSTO-IV and problems arising from the fact that enrolled patients were much sicker than typical UA/NSTEMI patients are likely to have biased the studies away from the null and make an assertion of benefit even more tenuous. Given the equivocal results, it would appear that the authors are relying on opinion rather than evidence to formulate their conclusions. Clinicians should understand that opinion and factors other than medical evidence may influence the content of the recommendations.