CORRESPONDENCE: LETTER TO THE EDITOR
Platelet Reactivity and Stent Thrombosis: Still Some Issues to Solve
Armando Perez de Prado, MD*,
Carlos Cuellas, MD,
Alejandro Diego, MD,
Antonio de Miguel, MD and
Felipe Fernandez-Vazquez, MD
* S. Cardiologia, Hospital de Leon, Altos de Nava SN, 24008 Leon, Spain (Email: aperez{at}secardiologia.es).
We read with great interest the recent article by Sibbing et al. (1). They concluded that low response to clopidogrel assessed with multiple electrode platelet aggregometry (MEA) is significantly associated with an increased risk of stent thrombosis. Considering the potential clinical implications of this attractive study, addressing some methodological issues would be appreciated.
The authors remark that the platelet aggregation measurements were not normally distributed, suggesting a right-skewed curve of the observed values. Different studies with smaller populations than the current one have shown a normal distribution of the platelet aggregation parameters with light transmission aggregometry (2,3) and point-of-care, VerifyNow P2Y12 assay (Accumetrics, San Diego, California) (4). In a previous publication (5), the authors demonstrated a good correlation between MEA and light transmission aggregometry results. Do the obtained values in that population fit a normal distribution? Can any distinctive methodological characteristics of the MEA system explain this finding?
Another intriguing observation, conflicting with the published evidence (6), is the significantly higher proportion of active smokers in the group of low (upper quintile) responders to clopidogrel. We should expect a higher rate of active smokers among patients presenting with acute myocardial infarction, which was also related to lower response in the current study. It would be very interesting to know the individual influence of these variables by performing a multivariate analysis considering lower response to clopidogrel as the dependent variable.
Stent thrombosis (ST) is probably the most feared complication after percutaneous coronary intervention, irrespective of the time of appearance. Early ST (acute and subacute) still occurs despite the aggressive use of antiplatelet agents. Apart from adherence to the antiplatelet treatment and platelet aggregation response, some factors have been correlated with ST (7): lower left ventricle ejection fraction, smaller diameter of the reference vessel, longer stent lengths, and lower final pressure to implant the stents. The authors of the present study (1) focus the statistical analysis on the relations of different demographic, clinical, and procedural variables with the platelet aggregation values obtained with MEA. However, no data about the relationship between those variables and ST is provided. Do the previously published or any other variables correlate with ST? It sounds plausible that procedural and angiographic variables may play an important role in the development of ST, especially in the case of early ST. A Cox proportional hazards model that includes the above-mentioned variables could be very helpful to detect all the independent predictors of ST.
We absolutely agree with the authors that low response to clopidogrel (or high post-treatment platelet reactivity) may identify patients at higher risk of stent thrombosis. But all the mechanisms and related factors should be clarified to better prevent ischemic cardiac events.
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1. Sibbing D, Braun S, Morath T, et al. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis J Am Coll Cardiol 2009;53:849-856.[Abstract/Free Full Text]2. Serebruany VL, Steinhubl SR, Berger PB, Malinin AI, Bhatt DL, Topol EJ. Variability in platelet responsiveness to clopidogrel among 544 individuals J Am Coll Cardiol 2005;45:246-251.[Abstract/Free Full Text] 3. Gurbel PA, Bliden KP, Hiatt BL, O'Connor CM. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity Circulation 2003;107:2908-2913.[Abstract/Free Full Text] 4. de Miguel Castro A, Cuellas Ramon C, Diego Nieto A, et al. Post-treatment platelet reactivity predicts long-term adverse events better than the response to clopidogrel in patients with non-ST-segment elevation acute coronary syndrome Rev Esp Cardiol 2009;62:126-135.[CrossRef][Web of Science][Medline] 5. Sibbing D, Braun S, Jawansky S, et al. Assessment of ADP-induced platelet aggregation with light transmission aggregometry and multiple electrode platelet aggregometry before and after clopidogrel treatment Thromb Haemost 2008;99:121-126.[Web of Science][Medline] 6. Bliden KP, Dichiara J, Lawal L, et al. The association of cigarette smoking with enhanced platelet inhibition by clopidogrel J Am Coll Cardiol 2008;52:531-533.[Abstract/Free Full Text] 7. Airoldi F, Colombo A, Morici N, et al. Incidence and predictors of drug-eluting stent thrombosis during and after discontinuation of thienopyridine treatment Circulation 2007;116:745-754.[Abstract/Free Full Text]
Related Article
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- Dirk Sibbing, Nicolas von Beckerath, and Adnan Kastrati
J. Am. Coll. Cardiol. 2009 54: 667-668.
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