Will Diabetes Save the Platelet Blockers?

More than 30 000 patients have been enrolled in trials assessing the efficacy of glycoprotein (GP) IIb/IIIa inhibitors in unstable angina (UA) or non–ST-segment elevation MI (NSTEMI). The initial trials demonstrated that the use of a GP IIb/IIIa inhibitor resulted in a significant decrease in the rate of death or nonfatal myocardial infarction.1,2 More recently, however, the GP IIb/IIIa inhibitor with the best track record to date in the setting of percutaneous coronary intervention (PCI), abciximab, was tested in UA/NSTEMI in the Global Use of Strategies To Open occluded coronary arteries in Acute Coronary Syndromes (GUSTO IV–ACS) trial, which enrolled patients in whom PCI was not intended, and showed no benefit.3 These disappointing results may have been related to issues of dosing, patient selection, and trial design, but nevertheless, they have led to a reappraisal of the utility of GP IIb/IIIa inhibitors in UA/NSTEMI.See p 2767 In the present issue of Circulation , Roffi and colleagues4 revive enthusiasm for the use of GP IIb/IIIa inhibitors in acute coronary syndromes (ACS). They wished to determine whether patients presenting with UA/NSTEMI who had diabetes mellitus derived particular benefit from GP IIb/IIIa inhibition. To answer this question, they performed a meta-analysis of the 6 major, placebo-controlled, GP IIb/IIIa inhibitor trials to date. Stratifying by diabetic status, they found that assignment to active treatment with a GP IIb/IIIa inhibitor was associated with a significant 26% reduction in mortality among diabetic patients, whereas there was no effect among nondiabetics. These results were consistent across all 6 trials, despite the use of different GP IIb/IIIa inhibitors.There is a priori biologic plausibility to support these intriguing results. Not only is diabetes mellitus a well-established risk factor for the development of atherosclerotic coronary artery disease, but compared with their nondiabetic counterparts, diabetic patients …