Danish Survey Finds Clopidogrel Less Effective in Diabetics

September 4th, 2012

Danish Survey Finds Clopidogrel Less Effective in Diabetics

Larry Husten, PHD

A large nationwide survey of MI survivors in Denmark provides new information about the efficacy of antiplatelet therapy with clopdiogrel in patients with diabetes. In a paper published in JAMA, Charlotte Andersson reports on 58,851 MI patients, 12% of whom had diabetes and 60% of whom received clopidogrel.

As expected, diabetics had a worse outcome than nondiabetics: the composite endpoint of recurrent MI and all-cause mortality occurred in 25% of diabetics compared with 15% of nondiabetics. Overall mortality was 17% in the diabetic group compared with 10% in the nondiabetic group.

Clopidogrel was less effective in diabetics than in nondiabetics in reducing all-cause mortality and CV mortality:

All-cause mortality risk reduction: 11% for diabetics versus 25% for nondiabetics (p value for interaction = 0.001)
CV mortality risk reduction: 7% (nonsignificant) for diabetics versus 23% for nondiabetics (p value for interaction = o.01)

The results lend support to the hypothesis that “there may be a difference of effect of clopidogrel among those with diabetes compared with those without it,” write the authors. After acknowledging that “use of clopidogrel may still translate into a significant reduction in event rates for patients with diabetes,” they then raise the “possibility that patients with diabetes may benefit from a more potent platelet inhibitor strategy to achieve a relative risk reduction similar to patients without diabetes.”

In an accompanying editorial, Deepak Bhatt lends support to their suggestion, writing that it is plausible to suspect that there is “something about patients with diabetes that makes them less likely to respond to standard antiplatelet therapy.” Compared with nondiabetics, diabetics with coronary artery disease have increased platelet reactivity. Bhatt writes that the newer and more potent antiplatelet agents prasugrel and ticagrelor may be more effective in diabetics, although they may also increase the risk for bleeding, and they cost more than clopidogrel, which has now gone generic.

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September 4th, 2012