Platelet Response to Clopidogrel May Be Decreased in Patients With Diabetes

Patients with diabetes undergoing coronary stent implantation for symptomatic acute coronary syndrome have a lower response to a 600-mg dose of clopidogrel, which was linked with a decrease in platelet response. "Type 2 diabetes is accompanied by platelet function disorders leading to an accelerated process of atherosclerosis and increased risk for atherothrombotic complications," write Tobias Geisler, MD, of the University Hospital Tübingen in Germany, and colleagues. "Recently, a high variability of response to clopidogrel measured by platelet function tests has been reported among patients with percutaneous coronary intervention (PCI), and hyporesponsiveness to clopidogrel has been considered to influence cardiac outcome in these patients."

Of 485 consecutively enrolled patients undergoing PCI, 161 (33.2%) had diabetes, 264 (54%) underwent an elective procedure for stable angina, and 221 (46.0%) were treated with PCI for acute coronary syndrome.

Posttreatment platelet reactivity to clopidogrel was lower in patients with diabetes (40.0% vs 31.8%; P = .01), but there was no significant effect of diabetes on collagen-induced aggregation.

In a subgroup of patients with coronary stenting for stable angina and patients with acute coronary syndrome, diabetic patients with acute coronary syndrome had significantly higher posttreatment aggregation than did nondiabetic patients with acute coronary syndrome.

In diabetic patients with acute coronary events, ADP-induced aggregation was highest 6 to 12 hours after clopidogrel was first administered. Thereafter, platelet inhibition was similar in diabetic and nondiabetic patients.

"Diabetic individuals with ACS [acute coronary syndrome] show a lower response to a 600-mg clopidogrel loading dose," the authors write. "We found type 2 diabetes to be associated with a decreased platelet response in a heterogeneous patient cohort with symptomatic CAD [coronary artery disease]. Although diabetic individuals frequently present with other cardiovascular risk factors (such as hypertonus and dyslipidemia) that contribute to chronic platelet activation, we could not observe a significant difference of these factors between diabetic and nondiabetic patients."

"Although diabetic patients benefit from the antithrombotic effects of clopidogrel, both previous and present data suggest that an intensified antiplatelet therapy in type 2 diabetic patients with acute coronary events might improve cardiovascular outcome," the authors conclude. "Further randomized trials are needed to demonstrate the clinical benefit of an intensified or alternative antiplatelet regimen (eg, novel antiplatelet substances such as prasugrel) in diabetic patients."

Diabetes Care. 2007;30:372-374.

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