Calcium-Channel Blockers Reduce the Antiplatelet Effect of Clopidogrel

Siller‐Matula, Jolanta M.; Lang, Irene M.; Christ, Guenter; Jilma, Bernd

doi:10.1016/j.jacc.2008.07.055

Cited by 235 publications

(76 citation statements)

References 43 publications

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“…Further factors that improved clopidogrel response were higher platelet counts, suggestive for a stable and sufficiently inhibited platelet population (low turnover) and no use of calcium channel blockers, which is in line with others [38], but contradicts recent findings [39].…”

Section: Discussionsupporting

confidence: 57%

Variability of on-treatment platelet reactivity in patients on clopidogrel

Freynhofer

Bruno²,

Brozovic³

et al. 2013

Platelets

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Response to clopidogrel therapy is subject to inter-individual variability. However, data with regard to on-treatment platelet reactivity over time in patients undergoing coronary stenting are scarce. For this prospective observational study, 102 consecutive patients on dual antiplatelet therapy undergoing coronary stenting due to stable coronary artery disease (CAD; n = 29), non ST-elevation acute coronary syndrome (NSTE-ACS; n = 45) and ST-elevation myocardial infarction (STEMI; n = 28) were enrolled. Vasodilator-stimulated phosphoprotein-phosphorylation assay was performed at baseline, as well as 1, 3 and 6 months thereafter. Platelet reactivity index (PRI) measured after 1, 3 and 6 months was lower compared to baseline values (p < 0.001). Variables responsible for reduced response to clopidogrel at baseline (reticulated platelet fraction, simvastatin therapy) and during steady-state phase (body mass index, blood glucose concentrations, cholesterol/HDL-ratio and quality of life score) were different. High on-treatment platelet reactivity (HTPR)-phenotype (cut-off = 50% PRI) within the first month changed in 31% of stable CAD, 33% of NSTE-ACS and 39% of STEMI patients, respectively. HTPR-phenotype in the steady-state phase (month 1 to 6) changed in 45% of stable CAD, 33% of NSTE-ACS and 25% of STEMI patients. Response to clopidogrel and accordingly platelet function might vary over time, especially when a cut-off based approach, is used. There was a significant reduction of on-treatment platelet reactivity within the first month after percutaneous coronary intervention with stenting which was maintained for up to 6 months. Variables associated with reduced response to clopidogrel at baseline and during steady-state phase were different, as the latter mainly reflected an unfavorable metabolic profile, comprising elevated BMI, blood glucose levels as well as cholesterol/HDL-ratio.

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Section: Discussionsupporting

confidence: 57%

Variability of on-treatment platelet reactivity in patients on clopidogrel

Freynhofer

Bruno²,

Brozovic³

et al. 2013

Platelets

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show abstract

“…Numerous risk factors, among them genetical, individual, or drug interaction dependent ones, have been discovered to be responsible for the phenomenon of clopidogrel inefficiency [4,5,7,8,10,11,13,14,16,17]. Platelet function testing to assess the effect of clopidogrel on platelet aggregation has thus undergone a rapid evolution.…”

Section: Discussionmentioning

confidence: 99%

“…One potential reason for this phenomenon is the loss of function allelic variations in the cytochrome P450 CYP2C19 gene shown to affect the bioavailability of the active metabolite of clopidogrel and to be predictive of adverse cardiovascular events, increased mortality and rates of definite stent thrombosis [4,6,7,9]. Furthermore, pharmacological interactions with statins [10,11], proton pump inhibitors [12,13] and calcium channel blockers [14] have been described to cause clopidogrel inefficiency. In addition, inter-and intra-individual differences in response to clopidogrel must be considered [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Clinical management of clopidogrel inefficiency by point of care platelet function testing and individual adjustment of anti-platelet therapy – initial experiences

et al. 2009

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Insufficient inhibition of ADP dependent platelet aggregation by clopidogrel is associated with an increased risk for adverse coronary events, such as stent thrombosis, after percutaneous coronary intervention. Here, we describe an approach to the clinical management of patients with insufficient inhibition of ADP dependent platelet aggregation by clopidogrel involving dose adjustment or switching of the thienoyridine. We put special emphasize on a patient who experienced recurrent acute myocardial infarction due to stent thrombosis associated with severe clopidogrel non response following elective coronary drug eluting stent implantation. In this patient, an inadequate clopidogrel effect at maintenance doses was confirmed by repeated platelet function assessment with a multiple electrode impedance point of care platelet function test. Subsequent dose adjustments still did not result in sufficient inhibition of ADP dependent platelet aggregation. Only after switching to the then shortly available new thienopyridine prasugrel could a sufficient platelet inhibition be obtained. However, our data from further patients show that although this may overcome inadequate clopidogrel efficiency in many cases, even under prasugrel suboptimal platelet inhibition may occur.

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“…A diminished pharmacodynamic response to clopidogrel has been observed with coadministration of proton pump inhibitors, lipophilic statins, warfarin, and calcium channel blockers, which are metabo-lized by enzymes also involved in clopidogrel metabolism (CYP2C19, CYP3A4, and CYP2C9). [60][61][62][63] Moreover, cigarette smoking and coadministration of Hypericum perforatum or rifampicin enhanced the antiplatelet response to clopidogrel through activation of CYP1A2 and CYP3A4, respectively. 64,65 The clinical consequences of these pharmacodynamic interactions remain controversial.…”

Section: Drug-drug Interactionsmentioning

confidence: 99%

Latest Evidence in Personalized Antiplatelet Therapy in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention

et al. 2012

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In patients with acute coronary syndromes undergoing percutaneous coronary intervention, the combination of aspirin and clopidogrel, a P2Y12 adenosine diphosphate (ADP) receptor antagonist, is the gold standard of antiplatelet therapy. Two more potent P2Y12 ADP receptor antagonists are now available. Pharmacodynamic studies have revealed a large interindividual variability in the biological response to clopidogrel that is primarily related to variable active metabolite generation, depending on clinical factors, drug-drug interactions, and genetic polymorphisms. Several assays to measure platelet function are available and have revealed a high prevalence of high on-treatment platelet reactivity (HTPR). Patients exhibiting HTPR after a clopidogrel loading dose have a higher risk of thrombotic recurrence after percutaneous coronary intervention. A recent consensus has defined HTPR for the main platelet assays available (using receiver operating characteristic curve analysis) to define the optimal cutoff value for each assay in order to predict thrombotic recurrences. In this article, we present several lines of evidence that suggest a therapeutic window of platelet reactivity inhibition with P2Y12 ADP receptor antagonists. Such a paradigm shift is supported by the results of the Platelet Inhibition and Patient Outcomes (PLATO) trial and the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38, which showed the superiority of ticagrelor and prasugrel on thrombotic events compared with clopidogrel; however, these 2 medications had an increased bleeding rate. With the results of these trials, in addition to the evidence of a therapeutic window with P2Y12 ADP receptor antagonists, we summarize the potential of platelet reactivity monitoring and pharmacogenomics to tailor therapy.

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Calcium-Channel Blockers Reduce the Antiplatelet Effect of Clopidogrel

Abstract: Coadministration of CCBs is associated with decreased platelet inhibition by clopidogrel.

Cited by 235 publications

References 43 publications

Variability of on-treatment platelet reactivity in patients on clopidogrel

Variability of on-treatment platelet reactivity in patients on clopidogrel

Clinical management of clopidogrel inefficiency by point of care platelet function testing and individual adjustment of anti-platelet therapy – initial experiences

Latest Evidence in Personalized Antiplatelet Therapy in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention

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