Clopidogrel treatment after myocardial infarction (MI) was associated with lower rates of all-cause death and cardiovascular death than non-clopidogrel users, but the difference in event rates was smaller in patients with diabetes than in non-diabetics, according to a study published on Sept. 4 in The Journal of the American Medical Association (JAMA).

The Danish study, which used a cohort of nearly 60,000 patients with first-time MI between 2002 and 2009, found a reduced one-year clinical effectiveness associated with clopidogrel treatment in diabetic patients. Specifically, in patients with diabetes who were treated with clopidogrel, the unadjusted mortality rates were 13.4 (95 percent CI, 12.8-14.0) vs. 29.3 (95 percent CI, 28.3-30.4) in patients who were not treated. In non-diabetic patients treated with clopidogrel, the unadjusted mortality rates were 6.4 (95 percent CI, 6.3-6.6) vs. 21.3 (95 percent CI, 21.0-21.7) for those not treated. However, clopidogrel was associated with less effectiveness for all-cause mortality (HR, 0.89 [95 percent CI, 0.79-1.00] vs. 0.75 [95 percent CI, 0.70-0.80]; P for interaction, .001) and for cardiovascular mortality (HR, 0.93 [95 percent CI, 0.81-1.06] vs. 0.77 [95 percent CI, 0.72-0.83]; P for interaction, .01) in diabetic patients vs. non-diabetic patients.

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According to the study authors, the findings support previous studies showing high platelet reactivity and diminished responsiveness to standard clopidogrel treatment in diabetic patients. "It should however be emphasized," they note, "that considering the relatively higher absolute risks found for patients with diabetes, use of clopidogrel may still translate into a significant reduction in event rates for patients with diabetes, which data from the subgroup analyses supported." They go on to suggest that patients with diabetes "may benefit from a more potent platelet inhibitor strategy to achieve a relative risk reduction similar to patients without diabetes."

However, Christopher Cannon, MD, FACC, from Brigham and Women's Hospital and editor-in-chief of CardioSource Science and Quality, noted, that caution should be used in interpreting these data since they are part of an observational study, comparing patients who are quite different (those treated vs. untreated with clopidogrel). As such, the differences in event rates may be due to patient differences (i.e., confounding) rather than being only attributable to the drug treatment.

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