Comparison of Platelet Reactivity and Periprocedural Outcomes in Patients With Versus Without Diabetes Mellitus and Treated With Clopidogrel and Percutaneous Coronary Intervention

Mangiacapra, Fabio; Patti, Giuseppe; Peace, Aaron; Gatto, Laura; Vizzi, Vincenzo; Ricottini, Elisabetta; D’Ambrosio, Andrea; Müller, Olivier; Barbato, Emanuele; Sciascio, Germano Di

doi:10.1016/j.amjcard.2010.04.015

Cited by 74 publications

(43 citation statements)

References 29 publications

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“…49 In patients with DM, prasugrel (60 mg plus 10 mg/day), even in comparison with 600 mg plus 150 mg daily dose of clopidooccurring in patients having both DM and HPR while on clopidogrel and the lowest in those without DM and without an impaired response to the drug. 44 Given the clinical relevance of interindividual variability in the response to standard clopidogrel doses, various studies have investigated the usefulness of higher clopidogrel loading and maintenance doses in patients undergoing PCI. The ARMYDA-2 study first showed that a 600-mg clopidogrel loading dose given 6 h before the procedure is associated with 52% reduction of early ischemic events compared with the conventional 300-mg dose.…”

Section: New Oral Antiplatelet Agents In Acs Patients With Dmmentioning

confidence: 99%

Antiplatelet Therapy in Patients With Diabetes Mellitus and Acute Coronary Syndrome

Patti

Proscia

Sciascio

2014

Circ J

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Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp iabetes mellitus (DM) represents a major public health concern because of its prevalence and the poorer cardiovascular prognosis of patients with this disease; thus, strategies aimed at improving cardiovascular outcomes in patients with DM may have relevant epidemiological, economic and clinical effects. Previous investigations in diabetic patients with acute coronary syndrome (ACS) showed a 1.8-fold increase in cardiovascular deaths and a 1.4-fold increase in myocardial infarctions (MI) at 2 years compared with nondiabetics. 1 Moreover, a gradient in the incidence of these events according to diabetes type has been demonstrated, as patients with insulin-dependent DM (IDDM) have a worse prognosis than those with non-IDDM. 2 Randomized evidence in the setting of ACS indicates that an invasive strategy with systematic coronary angiography and, when indicated, coronary revascularization, compared with a conservative strategy, is associated with more pronounced benefit in patients with vs. those without DM (27% vs. 13% risk reduction of events at 6 months in the TACTICS-TIMI 18 trial, although in that study the P-value for interaction was not significant). 3 Nevertheless, despite diabetic patients gaining the greatest advantage from an invasive strategy, after ACS in the real world they undergo early cardiac catheterization and percutaneous coronary intervention (PCI) less frequently than non-DM patients; 2 it is notable that rates of receiving an invasive approach are the lowest for ACS patients with IDDM. Biological Bases of Platelet Hyperreactivity in Patients With DMDifferent systems involved in the maintenance of vascular integrity and patency are impaired in DM, such as platelet and endothelial function, coagulation pathways and fibrinolysis. 4 Notably, platelets of patients with DM have been proven to be hyperreactive, which leads to intensified adhesion, activation and aggregation. 5, 6 Several mechanisms are involved in this platelet dysfunction (Figure 1): hyperglycemia enhances platelet aggregation by inducing P-selectin expression, 7 by activating protein kinase C (a mediator of platelet activation) 8 and by glycating platelet surface proteins, with consequent decrease in membrane fluidity and amplification of platelet adhesion. 9 Moreover, insulin resistance and/or deficiency in diabetic patients have been associated with impairment in the response to antithrombotic molecules (such as prostacyclin) 10 and contribute to platelet dysfunction by insulin receptor substrate-dependent effects, causing a rise in the intracellular calcium concentration and subsequent enhanced platelet degranulation. 11 Upregulation of glycoprotein (GP) IIb/IIIa surface receptors, 12 amplification of P2Y12 signaling, 13 and overproduction of reactive oxygen species 14 also contribute to the platelet dysfunction of diabetic patients; finally, metabolic conditions frequently associated with DM (ie, obesity, dyslipidemia and systemic i...

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Section: New Oral Antiplatelet Agents In Acs Patients With Dmmentioning

confidence: 99%

Antiplatelet Therapy in Patients With Diabetes Mellitus and Acute Coronary Syndrome

Patti

Proscia

Sciascio

2014

Circ J

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“…For some years, it has been known that the antiaggregant response of clopidogrel varies individually according to a number of factors such as genetics 4 , drug interactions 5,6 and clinical conditions such as diabetes 7 . The incapacity of clopidogrel to inhibit platelet aggregation measured at the laboratory is known as clopidogrel resistance 8 .…”

Section: Introductionmentioning

confidence: 99%

Resistência ao clopidogrel: prevalência e variáveis associadas

Silva¹,

Almeida²,

Neno³

et al. 2012

Arq. Bras. Cardiol.

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Background: The dual antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel is the cornerstone of treatment for patients undergoing angioplasty with coronary stent implantation. However, some of these patients, despite the use of aspirin and clopidogrel, are not effectively anti-aggregated, a phenomenon known as resistance to antiplatelet agents. Its prevalence, as well as the conditions associated with it, is unknown in our country.

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“…22 In patients with increased baseline concentrations of creatine kinase-MB, if the values are stable or falling, a subsequent increase ≥50% the baseline value fulfilled the criteria for periprocedural MI. 23, 24 Blood samples were drawn from all patients before PCI and at 24 h after intervention for measurement of creatine kinase-MB and troponin T concentrations.…”

Section: Main Outcomesmentioning

confidence: 99%

Association of CYP2C19 Genotype With Periprocedural Myocardial Infarction After Uneventful Stent Implantation in Chinese Patients Receiving Clopidogrel Pretreatment

Qian

Sun

et al. 2012

Circ J

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Background: High platelet reactivity (HPR) after clopidogrel treatment is linked to an increased risk of periprocedural myocardial infarction (PMI). The occurrence of PMI that could be associated with CYP2C19 genotype status was our hypothesis. Methods and Results:A total of 233 patients with non-ST elevation acute coronary syndromes (NSTACS) undergoing uneventful elective percutaneous coronary intervention were included. Platelet reactivity was assessed by Thrombelastograph at 24 h after 300 mg clopidogrel loading. HPR was defined as ≥70% adenosine diphosphateinduced platelet aggregation. The CYP2C19*2 and *3 loss-of-function (LOF) alleles were determined using DNA microarray method. Patients with PMI had significantly higher on-clopidogrel platelet reactivity compared to those without PMI (60.0±24.4% vs. 43.0±24.0%, P<0.001). HPR was more frequently observed in patients with PMI and was the strongest risk factor of PMI in multivariate analysis (ORadj=4.348, 95% CI: 1.846-10.241, P=0.001). Furthermore, the incidence of HPR was significantly associated with the carriage of 2 CYP2C19 LOF alleles. Compared with non-carriers, patients carrying 2 CYP2C19 LOF alleles had a 3.000-fold increased risk (95% CI: 1.071-8.400, P=0.037) for PMI in multivariate analysis. However, inclusion of HPR as a covariate in the regression model changed the significant relationship between the carriage of 2 CYP2C19 LOF alleles and PMI.Conclusions: Among Chinese patients with NSTACS, carriers with 2 CYP2C19 LOF alleles are more prone to HPR, which is associated with an increased risk for PMI. (Circ J 2012; 76: 2773 - 2778

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Comparison of Platelet Reactivity and Periprocedural Outcomes in Patients With Versus Without Diabetes Mellitus and Treated With Clopidogrel and Percutaneous Coronary Intervention

Cited by 74 publications

References 29 publications

Antiplatelet Therapy in Patients With Diabetes Mellitus and Acute Coronary Syndrome

Antiplatelet Therapy in Patients With Diabetes Mellitus and Acute Coronary Syndrome

Resistência ao clopidogrel: prevalência e variáveis associadas

Association of CYP2C19 Genotype With Periprocedural Myocardial Infarction After Uneventful Stent Implantation in Chinese Patients Receiving Clopidogrel Pretreatment

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