The impact of renal function on platelet reactivity and clinical outcome in patients undergoing percutaneous coronary intervention with stenting

2014 ◽  
Vol 112 (12) ◽  
pp. 1174-1181 ◽  
Author(s):  
Nicoline Breet ◽  
Corine de Jong ◽  
Willem Jan Bos ◽  
Jochem van Werkum ◽  
Heleen Bouman ◽  
...  

SummaryPatients with chronic kidney disease (CKD) have an increased risk of cardiovascular disease. Previous studies have suggested that patients with CKD have less therapeutic benefit of antiplatelet therapy. However, the relation between renal function and platelet reactivity is still under debate. On-treatment platelet reactivity was determined in parallel by ADP- and AA-induced light transmittance aggregometry (LTA) and the VerifyNow® System (P2Y12 and Aspirin) in 988 patients on dual antiplatelet therapy, undergoing elective coronary stenting. Patients were divided into two groups according to the presence or absence of moderate/severe CKD (GFR<60 ml/min/1.73 m2). Furthermore, the incidence of all-cause death, non-fatal acute myocardial infarction, stent thrombosis and stroke at one-year was evaluated. Patients with CKD (n=180) had significantly higher platelet reactivity, regardless of the platelet function test used. Patients with CKD more frequently had high on-clopidogrel platelet reactivity (HCPR) and high on-aspirin platelet reactivity (HAPR) regardless of the platelet function test used. After adjustment for potential confounders, this was no longer significant. The event-rate was the highest in patients with both high on-treatment platelet reactivity (HPR) and CKD compared to those with neither high on-treatment platelet reactivity nor CKD. In conclusion, the magnitude of platelet reactivity as well as the incidence of HPR was higher in patients with CKD. However, since the incidence of HPR was similar after adjustment, a higher rate of co-morbidities in patients with CKD might be the major cause for this observation rather than CKD itself. CKD-patients with HCPR were at the highest risk of long-term cardiovascular events.Clinical Trial Registration: www.clinicaltrials.gov: NCT00352014.

2018 ◽  
Vol 46 (5) ◽  
pp. 1866-1875 ◽  
Author(s):  
Masanori Tsujimoto ◽  
Yukiko Enomoto ◽  
Masafumi Miyai ◽  
Yusuke Egashira ◽  
Toru Iwama

Purpose To determine the best platelet function test for in-stent tissue protrusion following carotid artery stenting (CAS). Methods Patients who underwent CAS were recruited prospectively in this observational study. Combination of aspirin 100 mg/day and clopidogrel 75 mg/day was administered for a minimum of 7 days prior to procedure. Platelet aggregation was measured by light transmittance aggregometry (LTA) following stimulation by adenosine diphosphate (ADP), collagen, and thrombin receptor activating peptide (TRAP) and by the point of care assay, VerifyNow which measures aspirin and thienopyridine reaction units. Results In-stent tissue protrusion with maximum projection area of ≥1 mm2 was detected by optical coherence tomography (OCT) in 10/28 (36%) patients. Baseline characteristics were not significantly different between the two in-stent size groups (i.e., ≥1 mm2 vs. <1 mm2) but after stimulation by collagen at 10 and 20 μg/ml, platelet reactivity as measured by LTA was significantly higher in the ≥1 mm2 group compared with the <1 mm2 group. No other differences in platelet function were detected. Conclusions Collagen-induced platelet reactivity was related to in-stent tissue protrusion size following CAS.


2010 ◽  
Vol 5 (1) ◽  
pp. 96 ◽  
Author(s):  
Collet Jean-Philippe ◽  
Jochem Wouter van Werkum ◽  
◽  

Antiplatelet therapies are often used to minimise complications in patients with acute coronary syndromes or who are undergoing percutaneous coronary intervention with stenting. However, the occurrence of ‘high on-treatment platelet reactivity’ associated with the gold standard treatments aspirin and clopidogrel in a subset of individuals limits the efficacy of these drugs. This lack of response, which has been attributed to a genetic polymorphism, is associated with an increased risk of subsequent atherothrombotic events. In recent years, platelet function assays have been used to monitor antiplatelet inhibition. Various tests have been introduced that allow physicians to evaluate pharmacological response and potentially permit risk stratification of patients. While some of these assays have proved to be labour-intensive, the development of point-of-care assays may ease the time burden in clinical practice. Preliminary findings demonstrate the effectiveness of altering therapy based on assay results in terms of improving clinical outcomes, suggesting an important role for platelet function testing in the future of antiplatelet therapy.


2014 ◽  
Vol 112 (12) ◽  
pp. 1198-1208 ◽  
Author(s):  
Yongwhi Park ◽  
Udaya Tantry ◽  
Jong-Hwa Ahn ◽  
Kye Hwan Kim ◽  
Jin-Sin Koh ◽  
...  

SummaryAdjunctive use of phosphodiesterase (PDE) inhibitor can enhance antiplatelet and vasoprotective properties in patients with cardiovascular disease. The aim of this study was to evaluate the impact of PDE5 inhibitor dipyridamole on platelet function in stented patients with high platelet reactivity (HPR) during dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Patients with HPR after 600-mg clopidogrel loading were randomly assigned to adjunctive dipyridamole 75 mg twice daily to standard DAPT (DIP group; n = 45) or double-dose clopidogrel of 150 mg daily (DOUBLE group; n = 46) for 30 days. Platelet function was assessed at baseline and 30-day follow-up with platelet reactivity index (PRI) by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay and platelet aggregation (PA) by light transmittance aggregometry (LTA). Primary endpoint was PRI at 30-day follow-up. HPR was defined as PRI > 50%. Baseline platelet function did not differ between the groups. Following 30-day therapy, platelet function was significantly reduced in the DIP and DOUBLE groups (all p-values ≤ 0.004 and ≤ 0.068, respectively). PRI values were not significantly different between the two groups (mean difference: 3.1%; 95% confidence interval: –2.8% to 9.0%: p = 0.295). PA values and prevalence of HPR were similar between the groups. However, a significant number of patients still exhibited HPR in the DIP (75.6%) and DOUBLE (67.4%) groups. In conclusion, among stented HPR patients, adding dipyridamole to DAPT does not reduce platelet reactivity and prevalence of HPR compared with double-dose clopidogrel therapy, and therefore both strategies are inadequate to overcome HPR.


2015 ◽  
Vol 10 (7) ◽  
pp. 805-814 ◽  
Author(s):  
Emanuele Cecchi ◽  
Rossella Marcucci ◽  
Marco Chiostri ◽  
Valerio Mecarocci ◽  
Valentina Spini ◽  
...  

2010 ◽  
Vol 6 (1) ◽  
pp. 41 ◽  
Author(s):  
Collet Jean-Philippe ◽  
Jochem Wouter van Werkum ◽  
◽  

Antiplatelet therapies are often used to minimise complications in patients with acute coronary syndromes or who are undergoing percutaneous coronary intervention with stenting. However, the occurrence of ‘high on-treatment platelet reactivity’ associated with the gold standard treatments aspirin and clopidogrel in a subset of individuals limits the efficacy of these drugs. This lack of response, which has been attributed to a genetic polymorphism, is associated with an increased risk of subsequent atherothrombotic events. In recent years, platelet function assays have been used to monitor antiplatelet inhibition. Various tests have been introduced that allow physicians to evaluate pharmacological response and potentially permit risk stratification of patients. While some of these assays have proved to be labour-intensive, the development of point-of-care assays may ease the time burden in clinical practice. Preliminary findings demonstrate the effectiveness of altering therapy based on assay results in terms of improving clinical outcomes, suggesting an important role for platelet function testing in the future of antiplatelet therapy.


2011 ◽  
Vol 106 (08) ◽  
pp. 253-262 ◽  
Author(s):  
Dominick J. Angiolillo ◽  
Piera Capranzano ◽  
Jose Luis Ferreiro ◽  
Masafumi Ueno ◽  
Davide Capodanno ◽  
...  

SummaryCilostazol is a platelet inhibitor which when added to aspirin and clopidogrel has shown to reduce the risk of recurrent ischaemic events without an increase in bleeding. These clinical benefits have shown to be more pronounced in patients with diabetes mellitus (DM). However, it remains unknown whether cilostazol exerts different pharmacodynamic effects in patients with and without DM. This was a randomised, double-blind, placebo-controlled, cross-over pharmacodynamic study comparing platelet function in patients with and without DM on aspirin and clopidogrel therapy. Patients (n=111) were randomly assigned to either cilostazol 100 mg or placebo twice daily for 14 days and afterwards crossed-over treatment for another 14 days. Platelet function was performed at baseline, 14 days post-randomisation, and 14 days post-cross-over. Functional testing to assess P2Y12 signalling included flow cytometric analysis of phosphorylation status of vasodilatorstimulated phosphoprotein measured by P2Y12 reactivity index (PRI), light transmittance aggregometry and VerifyNow. Thrombin generation processes were also studied using thrombelastography. Significantly lower PRI values were observed following treatment with cilostazol compared with placebo both in DM and non-DM groups (p < 0.0001). The absolute between-treatment differences of PRI between groups was a 35.1% lower in patients with DM (p=0.039). Similar results were obtained using all other functional measures assessing P2Y12 signalling. Thrombin generation was not affected by cilostazol. Cilostazol reduces platelet reactivity both in patients with and without DM, although these pharmacodynamic effects are enhanced in patients with DM. Despite the marked platelet inhibition, cilostazol does not alter thrombin-mediated haemostatic processes, which may explain its ischaemic benefit without the increased risk of bleeding.


Blood ◽  
2017 ◽  
Vol 130 (6) ◽  
pp. 713-721 ◽  
Author(s):  
Alan D. Michelson ◽  
Deepak L. Bhatt

Abstract Antiplatelet therapy is of proven benefit in coronary artery disease and a number of other clinical settings. This article reviews platelet function, molecular targets of antiplatelet agents, and clinical indications for antiplatelet therapy before focusing on a frequent question to hematologists about the 2 most commonly used antiplatelet therapies: Could the patient be aspirin “resistant” or clopidogrel “resistant”? If so, should results of a platelet function test be used to guide the dose or type of antiplatelet therapy? Whether such guided therapy is of clinical benefit to patients has been a source of controversy. The present article reviews this subject in the context of 2 prototypical clinical cases. Available evidence does not support the use of laboratory tests to guide the dose of aspirin or clopidogrel in patients with so-called aspirin or clopidogrel “resistance.”


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