Glycemic control and clopidogrel response
Article Outline
We read with great interest the study from Singla et al,1 confirming that diabetic patients have lower clopidogrel response than nondiabetic patients and raising the interesting question of the mechanisms underlying lower clopidogrel efficiency in diabetes. The authors described a strong positive correlation between HbA1c and the maximal intensity of platelet aggregation in response to adenosine diphosphate, 5 and 20 μmol/L, and concluded to a contribution of glycemic control to the biologic efficacy of clopidogrel. Their data are in contrast to our previous published results.2 In a population of 112 well-phenotyped type 2 diabetic patients, treated with clopidogrel with no doubt of clopidogrel compliance, we did not find any relationship between glycemic control (fasting plasma glucose, mean blood glucose, and HbA1c) and adenosine diphosphate-induced platelet aggregation (10 μmol/L), nor with the platelet reactivity index of vasodilator-stimulated phosphoprotein. As HbA1c is not the best surrogate marker of recent glycemic environment of platelets (but of the preceding 3 months), we repeated platelet tests 1 week after near-normalization of glycemic control via continuous subcutaneous insulin infusion, and we found no significant change of platelet indexes. There are several reasons for this discrepancy between the 2 studies. The patient population studied here was rather small (only 36 diabetic patients and 16 well controlled). Furthermore, in the study of Singla et al, body mass index (BMI) was statistically different between the diabetic and the nondiabetic group (P = .002). High BMI has already been associated with poor biologic clopidogrel response3 and must be considered as a potential confounding factor. Whether there is a difference in BMI between the 2 subgroups HbA1c < or ≥7 g/dL is also unknown. Other confounders may be cited such as poor patients' compliance. Previous studies have shown that poor glycemic control is often due to noncompliance to oral treatment.4 This could explain the difference observed in platelet reactivity. Among other confounders, diabetes duration, fibrinogen levels, and CYP 2C19 genotypes might be important in clopidogrel response. To conclude, we must use with caution when drawing conclusions about the link between glycemic control and platelet reactivity. Further studies are warranted to confirm the results of Singla et al. We thank the authors for this interesting study.
References
- The relation between platelet reactivity and glycemic control in diabetic patients with cardiovascular disease on maintenance aspirin and clopidogrel therapy. Am Heart J. 2009;158:784.e1–784.e6
- Enhanced post-clopidogrel platelet reactivity in diabetic patients is independently related to plasma fibrinogen level but not to glycemic control. J Thromb Haemost. 2009;7:1939–1941
- Relationship between aspirin and clopidogrel responses in acute coronary syndrome and clinical predictors of non response. Thromb Res. 2009;123:597–603
- . Influence of oral antidiabetic drugs compliance on metabolic control in type 2 diabetes. A survey in general practice. Diabetes Metab. 2003;29:79–81
PII: S0002-8703(10)00247-4
doi:10.1016/j.ahj.2010.03.021
© 2010 Mosby, Inc. All rights reserved.
Refers to article:
- The relation between platelet reactivity and glycemic control in diabetic patients with cardiovascular disease on maintenance aspirin and clopidogrel therapy
