Clopidogrel associated with decreased benefit in diabetics post-MI

Diabetics benefit less from receiving clopidogrel after myocardial infarction (MI) than non-diabetics, a study found.

To estimate the clinical effectiveness associated with clopidogrel treatment after MI in patients with diabetes, Danish researchers reviewed registry data for patients hospitalized for their heart attack who had survived 30 days after discharge and had not undergone coronary artery bypass surgery.

Results appeared in the Sept. 5 Journal of the American Medical Association.

Of the 58,851 patients included in the study, 7,247 (12%) had diabetes and 35,380 (60%) received clopidogrel. In total, 1,790 patients (25%) with diabetes and 7,931 patients (15%) without diabetes met the composite end point of recurrent MI and all-cause mortality.

In the overall study population, 978 patients with diabetes (80%) and 4,100 patients without diabetes (76%) died of cardiovascular events. Diabetics who were treated with clopidogrel had an unadjusted mortality rate of 13.4 events per 100 person-years (95% CI, 12.8 to 14.0 events per 100 person-years) compared to 29.3 events per 100 person-years (95% CI, 28.3 to 30.4 events per 100 person-years) for untreated diabetics. Non-diabetics treated with clopidogrel had unadjusted mortality rates of 6.4 events per 100 person-years (95% CI, 6.3 to 6.6 events per 100 person-years) compared to 21.3 events per 100 person-years (95% CI, 21.0 to 21.7 events per 100 person-years) for those not treated.

The researchers concluded that clopidogrel was associated with:

• less reduction in all-cause mortality in diabetics compared to non-diabetics (hazard ratio [HR], 0.89 [95% CI, 0.79 to 1.00] vs. 0.75 [95% CI, 0.70 to 0.80]; P for interaction, 0.001),
• less reduction in cardiovascular mortality in diabetics compared to non-diabetics (HR, 0.93 [95% CI, 0.81 to 1.06] vs. 0.77 [95% CI, 0.72 to 0.83]; P for interaction, 0.01) and
• no reduction in the composite end point in diabetics compared to non-diabetics (HR, 1.00 [95% CI, 0.91 to 1.10] vs. 0.91 [95% CI, 0.87 to 0.96]; P for interaction, 0.08).

Although head-to-head trials are needed, the study authors speculated that based on other published data, “[P]rasugrel may constitute an attractive alternative to clopidogrel in patients with diabetes with acute coronary syndromes, especially if recurrent ischemic events have occurred during clopidogrel treatment.”

An editorialist noted that evidence on the effects of various antiplatelet options in diabetics is still developing, but that it's clear these patients face a higher risk of adverse events after MI. “At least a portion of this excess risk appears due to platelet activity and function and to the effects of antiplatelet medications in patients with diabetes. Therefore, in appropriately selected patients, intensification of the antiplatelet regimen may be one method by which their outcomes might be markedly improved,” the editorial concluded.