HealthDay News — Patients with diabetes who are prescribed clopidogrel (Plavix) after a heart attack may not benefit as much as those without diabetes, study results suggest.

Reductions in all-cause mortality were lower among patients with diabetes compared with other clopidogrel users — 7% vs. 23% (P=0.01 for interaction) — Charlotte Andersson, MD, PhD, of Gentofte Hospital in Hellerup, Denmark, and colleagues, reported in the Journal of the American Medical Association.

“Patients with diabetes have an increased risk of ischemic adverse events and death compared with patients without diabetes,” the researchers wrote in background information included in the study. “Pharmacodynamic studies have shown that persistently high platelet reactivity is common in patients with diabetes in spite of clopidogrel treatment. Clinical trials have not convincingly demonstrated that clopidogrel benefits patients with diabetes as much patients without diabetes.”

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To further understand outcomes associated with clopidogrel treatment after heart attack in patients with and without diabetes, Andersson and colleagues analyzed data from the Danish National Patient Register. This included 58,851 patients hospitalized with incident myocardial infarction (MI) who had survived and had not undergone coronary artery bypass (CABG) 30 days after discharge from 2002 to 2009.

Follow-up was performed for one year. Outcomes examined included all-cause mortality, cardiovascular mortality, and a composite end point of recurrent heart attack and all-cause mortality.

Among the 58,851 patients included in the analysis —7,247 of whom (12 percent) had diabetes — 35,380 (60%) received clopidogrel at the beginning of the study.

During the study period, recurrent MI occurred in 1,790 patients with diabetes (25%) and 7,931 patients without diabetes (15%); of these, 1,225 with (17%) and 5,377 without diabetes (10%) died. Of the patients who died, 978 patients (80%) with diabetes and 4,100 patients (76%) without diabetes died of CV-related events.

Among the 12% of patients with diabetes, the researchers observed significantly less benefit for recurrent MI and all-cause mortality among patients prescribed clopidogrel compared with those who were not (HR=1.00 vs. 0.91; P=0.08 for interaction).

However, the researchers did not observe significant differences in clopidogrel benefits on any enpoint among patients who underwent per utaneous coronary intervention (PCI), regardless of diabetes status.

“It should however be emphasized 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,” the researchers noted. “Available data nevertheless raise a 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 L. Bhatt, M.D., MPH., of the VA Boston Healthcare System, Brigham and Women’s Hospital, and Harvard Medical School, Boston, wrote that more needs to be done to reduce all-cause and CV-associated mortality after a heart attack among patients with diabetes.

“[I]n appropriately selected patients, intensification of the antiplatelet regimen may be one method by which their outcomes might be markedly improved,” Bhatt wrote. 


  1. Andersson C et al. JAMA 2012; 308:882-889.
  2. Bhatt DL. JAMA. 2012; 308:921-922.