bleeding rate increased. With respect to patients undergoing PCI, the Clopidogrel for the Reduction of Events During Observation (CREDO) study randomized patients either to a 300-mg loading dose followed by 12 months of clopidogrel therapy or to no loading dose and clopidogrel treatment for 1 month on top of aspirin. Among 560 diabetic patients, the benefit of pretreatment and prolonged clopidogrel therapy was modest (RRR = 11.2%) compared with the benefit of this regimen observed among 1556 patients without diabetes (RRR = 32.8%).112
In the setting of non-ST-elevation ACS, aspirin remains a cornerstone of therapy, although specific data for diabetic patients are lacking. The Clopido-grel in Unstable angina to prevent Recurrent Events (CURE) trial randomized patients with ACS primarily medically managed to aspirin or aspirin plus clopi-dogrel for 9 to 12 months. Diabetic patients (n = 2840) derived only a modest, nonsignificant benefit from the combined treatment (death, MI, or stroke rate = 14.2% versus 16.7%). Among patients undergoing PCI in the trial, the benefit of the combined antiplatelet therapy was less marked (RR = 0.77) among diabetic patients compared with nondiabetic ones (RR = 0.66).113 With respect to STEMI, the ClOpi-dogrel and Metoprolol in Myocardial Infarction Trial (COMMIT) in China randomized 45,852 patients with suspected acute MI to clopidogrel on top of aspirin or aspirin alone for a mean of 15 days.114 Allocation to clopidogrel led to a modest but statistically significant relative risk reduction (9%) in death, reinfarction, or stroke during the treatment period. Limitations of the study included the lack of reperfusion therapy (approximately 50% received fibrinoly-sis, but primary PCI was performed only in isolated cases). No information on diabetic patients has so far been reported.
The CLopidogrel as Adjunctive Reperfusion TherapY (CLARITY)-TIMI 28 trial randomized patients receiving fibrinolytic therapy for acute MI to clopi-dogrel (300-mg loading dose followed by 75 mg/day) or placebo. At 30 days, the incidence of CV death, recurrent MI, or recurrent ischemia leading to urgent revascularization was reduced by 20% in those receiving clopidogrel therapy.115 No subgroup analysis addressing the diabetic patients enrolled in the main trial (n = 575) is currently available. Nevertheless, among the 282 diabetic patients who underwent PCI during their index hospitalization, pretreatment with clopidogrel resulted in a 39% reduction in 30-day events, although this difference was not statistically significant owing to the small sample size.116 Because of the results of the COMMIT and CLARITY-TIMI 28 trials, the U.S. Food and Drug Administration expanded the indications of clopidogrel for STEMI in August 2006. Overall, clopidogrel treatment for up to 1 year is indicated in diabetic patients presenting with ACS or undergoing PCI. Conversely, its role in the long-term prevention setting still needs to be defined. Although resistance to both aspirin and clopidogrel has been described in diabetic patients, the clinical relevance of these findings remains unde termined. Newer P2Y12 antagonists that have reversible action or are suitable for intravenous administration are currently being tested. Data on the diabetic population are lacking.
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