Platelet and coagulation abnormalities contribute to the development of CAD in diabetic patients. Results from diverse randomized clinical trials support the use of antiplatelet therapy in all diabetic patients. A meta-analysis of the Antiplatelet Trialists' Collaborative Group included over 47,000 patients (of whom approximately 10% were diabetics) and demonstrated an important benefit of aspirin therapy in diabetics with, or at increased risk for, vascular disease. The combined endpoint of vascular death, MI, or stroke was 22.3% in the control group and 18.5% in the aspirin group. The magnitude of benefit was similar in both diabetic -o and nondiabetic patients, and there was no evidence of excess bleeding in the former group. A preliminary report from the CURE trial investigators showed a S
significant 25% relative risk reduction in the composite endpoint of death and MI in 12,562 patients with acute coronary syndromes who were randomized to <j aspirin plus clopidogrel and compared with aspirin alone for up to 9 months of Ji blinded therapy. The favorable treatment effects were seen across all subgroups of patients studied, including patients with diabetes.
Clinical trials with low-molecular-weight heparins (LMWH) indicate that these agents are more effective than placebo and as beneficial as, if not superior to, standard unfractionated heparin (UFH) in the management of patients with non-ST-segment elevation acute coronary syndromes (unstable angina or non-Q-wave MI). For the most part, these studies demonstrate a consistent treatment benefit among patient subgroups. The ESSENCE trial demonstrated comparable benefits among diabetics and nondiabetics. In the TIMI-11B trial, enoxaparin was found to be superior to UFH in preventing cardiac death and nonfatal cardiac events (MI and unstable angina). Beneficial effects of enoxaparin were greatest in high-risk patients. In the GUSTO IIB trial, hirudin, a direct thrombin inhibitor, was more effective than UFH in the treatment of diabetic patients who presented with an acute coronary syndrome (ACS) and was not associated with increased risk of bleeding.
Results from randomized trials provide strong evidence that platelet glycoprotein (GP) IIb/IIIa inhibitors reduce the early and short-term incidence of death, MI, and recurrent angina in patients who present with non-ST-segment elevation acute coronary syndromes. In the PRISM-PLUS study, the benefit associated with tirofiban plus heparin in reducing cardiac events compared to heparin alone was comparable for both diabetic and nondiabetic subjects. Importantly, combination therapy of tirofiban plus heparin compared with heparin alone reduced significantly the secondary endpoint of death and MI much more profoundly in the diabetic subjects compared with that in the overall study population (88% vs. 43%; p = 0.005). In the PURSUIT trial, death and nonfatal MI were also significantly reduced by eptifibatide compared to placebo in both diabetic and non-diabetic subgroups of non-ST-segment elevation ACS. However, compared to nondiabetic patients, 30-day mortality was reduced to a greater extent in insulin-requiring diabetic patients. A meta-analysis that pooled diabetic patients from 10 recent trials of GP IIb/IIIa inhibitors revealed that diabetics had twice the absolute reduction in cardiac event rates compared to nondiabetics. There was a strong trend favoring an interaction between DM and the use of GP IIb/IIIa agents, but this did not reach statistical significance. The role of this class of agents when used adjunctively during PCI will be discussed in the section that details outcomes among diabetics who undergo myocardial revascularization.
4. Beta-Blockers g s
Pooled data from several trials of beta-blockers administered as secondary pre- S
vention post-MI demonstrate an overall 25% mortality reduction and a 29% g reduction in reinfarction. Diabetic subjects exhibit an almost threefold greater <j reduction in mortality compared to nondiabetics (37% vs. 13%). A similar M reduction in the incidence of reinfarction was apparent in those with and without diabetes. The results unquestionably underscore the important role of beta- a
& u blocker therapy after MI in diabetic patients. Unless there is an overt contraindication, all diabetic patients with prior MI or established CAD should receive a beta-blocker as part of a standard secondary prevention regimen.
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