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Aims:
Chronic kidney disease (CKD) is associated with increased thrombotic events and seems to influence platelet reactivity. Conflicting results have been published on platelet response in CKD patients with stable coronary artery disease. The aim of our study was to investigate the impact of CKD on platelet aggregation in acute coronary syndrome...
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Objective:
Combination of dual antiplatelet therapy (DAPT) with glycoprotein (GP) IIb/IIIa inhibitors can increase bleeding risk. In this study, we aimed to investigate bleeding complications of different DAPTs with concomitant tirofiban use in patients with acute coronary syndrome (ACS).
Methods:
This retrospective study included 224 consecutiv...
Background
The ADAPTABLE (Aspirin Dosing: A Patient‐Centric Trial Assessing Benefits and Long‐Term Effectiveness) was a large, pragmatic, randomized controlled trial that found no difference between high‐ versus low‐dose aspirin for secondary prevention of atherosclerotic cardiovascular disease. Whether concomitant P2Y12 inhibitor therapy modifies...
Purpose
P2Y12 receptor inhibitors are drugs that decrease the risk of stent thrombosis and lower the long-term risk of non-stent-related myocardial infarction and stroke. They inhibit the binding of adenosine diphosphate (ADP) to the P2Y12 receptor and effectively reduce platelet reactivity. However, considerable variability in the pharmacodynamics...
Introduction: Dual antiplatelet therapy (DAPT), vital post-percutaneous coronary intervention (PCI) to prevent cardiovascular events (CVEs) via aspirin and P2Y12 receptor antagonists, faces controversy when combined with proton pump inhibitors (PPIs) due to potential impacts on bleeding risk and antiplatelet efficacy, prompting the need for further...
Background
Clinical trials indicate that fentanyl, like morphine, may impair intestinal absorption and thus decrease the efficacy of oral P2Y12 inhibitors, such as clopidogrel, ticagrelor, and prasugrel. However, the ability of fentanyl to directly negate or reduce the inhibitory effect of P2Y12 receptor antagonists on platelet function has not bee...
Citations
... The chronic kidney disease was reported to be independent predictor of stent thrombosis in patients undergoing PCI therapy [7,8], which might be associated with weakened efficacy of the antiplatelet agents [9][10][11]. ESRD patients have to receive hemodialysis after several years, and it is controversial whether hemodialysis has an effect on the efficacies of the antiplatelet agents [12,13]. ...
It is controversial whether hemodialysis affects the efficacy of the antiplatelet agents. We aimed to investigate the impact of hemodialysis on efficacies of the antiplatelet agents in coronary artery disease (CAD) patients complicated with end-stage renal disease (ESRD). 86 CAD patients complicated with ESRD requiring hemodialysis were consecutively enrolled. After 5-day treatment with aspirin and clopidogrel or ticagrelor, the platelet aggregations induced by arachidonic acid (PLAA) or adenosine diphosphate (PLADP), and the P2Y12 reaction unit (PRU) were measured before and after hemodialysis. The propensity matching score method was adopted to generate a control group with normal renal function from 2439 CAD patients. In patients taking aspirin, the PLAA remained unchanged after hemodialysis. In patients taking clopidogrel, the PLADP (37.26 ± 17.04 vs. 31.77 ± 16.09, p = 0.029) and corresponding clopidogrel resistance (CR) rate (23 [48.9%] vs. 14 [29.8%], p = 0.022) significantly decreased after hemodialysis, though PRU remained unchanged. Subgroup analysis indicated that PLADP significantly decreased while using polysulfone membrane (36.8 ± 17.9 vs. 31.1 ± 14.5, p = 0.024). In patients taking ticagrelor, PLADP, and PRU remained unchanged after hemodialysis. ESRD patients had higher incidences of aspirin resistance (AR) and CR compared to those with normal renal function (AR: 16.1% vs. 0%, p = 0.001; CR: 48.4% vs. 24.8%, p = 0.024). Hemodialysis does not have negative effect on the efficacies of aspirin, clopidogrel and ticagrelor in ESRD patients with CAD. ESRD patients have higher incidences of AR and CR compared with those with normal renal function.
Trial registration ClinicalTrials.gov Identifier: NCT03330223, first registered January 4, 2018.
... A recent study also found that moderate-severe CKD (eGFR < 60 mL/min per 1.73m 2 ) was associated with an increased incidence of HRPR during clopidogrel treatment in patients with ACS treated with dual antiplatelet therapy. [13] And in this study, a re-analysis excluding patients treated with clopidogrel found no statistical difference in platelet reactivity between patients with normal and abnormal eGFR [13]. This finding suggests that HRPR in CKD may be associated only with clopidogrel and not with other P2Y12 inhibitors. ...
... A recent study also found that moderate-severe CKD (eGFR < 60 mL/min per 1.73m 2 ) was associated with an increased incidence of HRPR during clopidogrel treatment in patients with ACS treated with dual antiplatelet therapy. [13] And in this study, a re-analysis excluding patients treated with clopidogrel found no statistical difference in platelet reactivity between patients with normal and abnormal eGFR [13]. This finding suggests that HRPR in CKD may be associated only with clopidogrel and not with other P2Y12 inhibitors. ...
Introduction:
There are few studies on the relationship between the occurrence of clopidogrel-related high residual platelet reactivity (HRPR) and estimated glomerular filtration rate (eGFR) at admission in patients with ischemic stroke. The aim of this study was to investigate the possible relationship between the two.
Methods:
Patients who were hospitalized and diagnosed with acute ischemic stroke were recruited from 1 July 2017 to 30 June 2018 at Shanghai TCM-Integrated Hospital. Renal function was measured within 24 h of enrolment and eGFR was calculated. Patients were tested for platelet reactivity using the VerifyNow System after 7 days of antiplatelet therapy with clopidogrel 75 mg/d alone, and patients with P2Y12 reaction unit values ≥ 230 were diagnosed as HRPR. The association between HRPR and eGFR was analyzed.
Results:
A total of 274 patients were enrolled in the study, of whom 91 (33.21%) had HRPR. Multivariate logistic regression analysis suggested that an increased risk of HRPR was independently associated with female sex and reduced eGFR (female sex: OR=2.24, 95% CI: 1.26-3.99, P=0.006; mild CKD: R=2.95, 95% CI: 1.47-5.93, P=0.002; moderate CKD: OR=3.07, 95% CI: 1.08-8.75, P=0.04).
Conclusion:
Decreased eGFR is an independent risk factor for the occurrence of HRPR in patients with ischemic stroke.
... Preoperative dual antiplatelet therapy (DAT) (aspirin 100 mg and clopidogrel 75 mg daily) is currently recognized as a viable antiplatelet regimen, but ischemic events still occur in 6.0% to 7.3% of procedures and lead to varying degrees of disability and mortality [4,5]. Several studies have shown that some patients do not respond well to antiplatelet drugs, and possible reasons include genetic polymorphisms, advanced age, diabetes, renal insufficiency, and drug-drug interactions [6][7][8]. Identifying patients with poor antiplatelet responses prior to PED implantation and administering appropriate alternative antiplatelet agents may help to reduce ischemic events. ...
To analyze the effect of tirofiban on ischemic events in CYP2C19 loss-of-function (LOF) allele carriers during pipeline embolization device (PED) implantation. Demographic information, imaging data, ischemic complications, CYP2C19 genotyping, and platelet function test results were collected from patients with PED-treated intracranial aneurysms at three centers. Multivariate logistic regression was used to analyze risk factors for ischemic events. Patients were grouped according to LOF alleles and antiplatelet drugs, the baseline information of LOF allele carriers and non-carriers were compared, and the efficacy of tirofiban was analyzed by comparing the incidence of ischemic events in each group. In total, 278 patients were included in the study, 24 of whom had an ischemic event. 157 (56.5%) patients carried the LOF allele and were more likely to develop resistance to clopidogrel (P < 0.001) and hypertension (P = 0.010). Multivariate logistic regression analysis revealed that the independent risk factors for ischemic events were age of > 55 years (OR = 3.308, P = 0.028), LOF alleles (OR = 3.960, P = 0.036), and clopidogrel nonresponsiveness (OR = 3.301, P = 0.014). For LOF allele carriers, prophylactic use of tirofiban after PED implantation helped to reduce ischemic events (4.3% vs. 16.4%, P = 0.039). This study supports CYP2C19 genotyping before flow diversion because LOF alleles increase the risk of ischemic events. Prophylactic use of tirofiban may help reduce ischemic events in LOF allele carriers.
... 6 7 However, some patients with resistance to antiplatelet therapy (mainly clopidogrel) show high on-treatment platelet reactivity (HTPR), which could be due to CYP2C19 genotype polymorphisms, drug interactions, and chronic diseases such as diabetes and chronic kidney disease. [8][9][10][11] Therefore, identifying patients with HTPR with corresponding adjustments WHAT IS ALREADY KNOWN ON THIS TOPIC ⇒ Light transmission aggregometry (LTA) and CYP2C19 genotype testing are used to evaluate the antiplatelet effect of clopidogrel. We compared the predictive ability of the two methods for ischaemic complications in interventional therapy for intracranial aneurysms. ...
Background and purpose
Light transmission aggregometry (LTA) and CYP2C19 genotype analysis are commonly used to evaluate the antiplatelet effects of clopidogrel during the interventional treatment of intracranial aneurysms. The aim of this study was to determine which test can predict ischaemic events during these treatments.
Methods
Patient demographic information, imaging data, laboratory data and ischaemic complications were recorded. LTA and CYP2C19 genotype results were compared, and multiple linear regression was performed to examine factors related to platelet reactivity. Multivariate regression analysis was performed to determine whether LTA and CYP2C19 could predict ischaemic complications and to identify other clinical risk factors. Receiver operating characteristic curve analysis was conducted to calculate the cut-off value for predicting ischaemic complications. A subgroup analysis was also performed for different CYP2C19 genotype metabolisers, as well as for patients with flow diverters and traditional stents.
Results
A total of 379 patients were included, of which 22 developed ischaemic events. Maximum platelet aggregation induced by ADP (ADP-MPA) could predict ischaemic events (p<0.001; area under the curve, 0.752 (95% CI 0.663 to 0.842)), and its cut-off value was 41.5%. ADP-MPA (p=0.001) and hypertension duration >10 years (p=0.022) were independent risk factors for ischaemic events, while the CYP2C19 genotype was not associated with ischaemic events. In the subgroup analysis, ADP-MPA could predict ischaemic events in fast metabolisers (p=0.004) and intermediate metabolisers (p=0.003). The cut-off value for ischaemic events was lower in patients with flow diverters (ADP-MPA=36.4%) than in patients with traditional stents (ADP-MPA=42.9%).
Conclusions
ADP-MPA can predict ischaemic complications during endovascular treatment of intracranial aneurysms. Patients with flow diverters require stronger antiplatelet medication than patients with traditional stents.
... Other clinical factors, such as chronic kidney disease, diabetes or proton pump inhibitor co-administration, probably do not affect the efficacy of ticagrelor therapy [88,90,91]. ...
Novel P2Y12 ADP receptor blockers (ADPRB) should be preferred in dual-antiplatelet therapy in patients with acute coronary syndrome. Nevertheless, there are still patients who do not respond optimally to novel ADP receptor blocker therapy, and this nonoptimal response (so-called “high on-treatment platelet reactivity” or “resistance”) could be connected with increased risk of adverse ischemic events, such as myocardial re-infarction, target lesion failure and stent thrombosis. In addition, several risk factors have been proposed as factors associated with the phenomenon of inadequate response on novel ADPRB. These include obesity, multivessel coronary artery disease, high pre-treatment platelet reactivity and impaired metabolic status for prasugrel, as well as elderly, concomitant therapy with beta-blockers, morphine and platelet count for ticagrelor. There is no literature report describing nonoptimal therapeutic response on cangrelor, and cangrelor therapy seems to be a possible approach for overcoming HTPR on prasugrel and ticagrelor. However, the optimal therapeutic management of “resistance” on novel ADPRB is not clear and this issue requires further research. This narrative review article discusses the phenomenon of high on-treatment platelet reactivity on novel ADPRB, its importance in clinical practice and approaches for its therapeutic overcoming.
... Ticagrelor or prasugrel, both of which are potent oral P2Y12 receptor inhibitors, are recommended for the treatment of patients with ACS and CKD due to their rapid onset of action and high rate of platelet inhibition compared to clopidogrel [3][4][5]. Clopidogrel has a delayed onset of effect and wide interindividual variability in biological efficacy leading to a 40% rate of high on-treatment platelet reactivity (HTPR) [6,7]. Importantly, CKD patients have a greater risk of HTPR than the overall population, which was linked to thrombotic events and death [8,9]. ...
... Patients with ACS and CKD have a high thrombotic risk related to 3 main factors: alteration of the coagulation cascade, endothelial injury, and platelet alteration [4]. Patients with CKD have greater ADP-induced platelet aggregation, and the degree of reduction in clopidogrel response increases with renal insufficiency [7]. From a biological point of view, ticagrelor has a more rapid onset of action and induces a more potent and reproducible platelet inhibition than clopidogrel [12,27]. ...
Background:
Current guidelines recommend the use of potent antiplatelet agents in patients undergoing percutaneous coronary intervention (PCI) following an acute coronary syndrome (ACS). However, data about optimal platelet inhibition in severe renal insufficiency patients are scarce. The purpose of this study is to determine if ticagrelor is more effective than clopidogrel in patients with ACS and severe renal insufficiency treated with PCI.
Methods:
We retrospectively enrolled patients with ACS and severe renal insufficiency (eGFR ≤ 30 ml/min·1.73 m2 or dialysis) who underwent PCI at our hospital between January 2015 and March 2020. We used the adjusted Cox proportional hazards models to analyze the 1-year outcome endpoints, including the primary endpoint (the composite of cardiovascular death, recurrence of MI, or nonfatal ischemic stroke), death from any cause, and bleeding events (Bleeding Academic Research Consortium, BARC criteria).
Results:
A total of 276 patients with ACS and severe renal insufficiency who were treated with PCI with ticagrelor (n = 108) or clopidogrel (n = 168) were included in the study. After adjustment, there was no statistical difference in risk of the primary endpoint (HR, 0.78; 95% CI, 0.46-1.33; P=0.367) and death from any cause (HR, 0.86; 95% CI, 0.38-1.89; P=0.708) in the ticagrelor group against the clopidogrel group. However, the risk of total bleeding was significantly higher in the ticagrelor group (HR, 3.01; 95% CI, 1.81-5.62; P=0.01). Subgroup analysis according to the confounders did not identify any significant subgroup heterogeneity.
Conclusion:
Ticagrelor did not improve the major adverse cardiovascular events and all-cause mortality when compared to clopidogrel, but significantly increased the risk of bleeding in Chinese patients with ACS and severe renal insufficiency undergoing PCI.
... Although in recent decades much progresses has been made in our understanding of the genetic basis of platelet function and the mechanisms of antiplatelet therapy resistance [82][83][84], as well as the genetic background of AMI and its complications [85][86][87], coronary microvascular dysfunction still affects almost 50% of patients with AMI, even after prompt epicardial recanalization of the infarct-related artery by pPCI and optimal antiplatelet therapy [88]. ...
The significant reduction in ‘ischemic time’ through capillary diffusion of primary percutaneous intervention (pPCI) has rendered myocardial-ischemia reperfusion injury (MIRI) prevention a major issue in order to improve the prognosis of ST elevation myocardial infarction (STEMI) patients. In fact, while the ischemic damage increases with the severity and the duration of blood flow reduction, reperfusion injury reaches its maximum with a moderate amount of ischemic injury. MIRI leads to the development of post-STEMI left ventricular remodeling (post-STEMI LVR), thereby increasing the risk of arrhythmias and heart failure. Single pharmacological and mechanical interventions have shown some benefits, but have not satisfactorily reduced mortality. Therefore, a multitarget therapeutic strategy is needed, but no univocal indications have come from the clinical trials performed so far. On the basis of the results of the consistent clinical studies analyzed in this review, we try to design a randomized clinical trial aimed at evaluating the effects of a reasoned multitarget therapeutic strategy on the prevention of post-STEMI LVR. In fact, we believe that the correct timing of pharmacological and mechanical intervention application, according to their specific ability to interfere with survival pathways, may significantly reduce the incidence of post-STEMI LVR and thus improve patient prognosis.
Background It is controversial whether hemodialysis affects the efficacy of the antiplatelet agents. We aimed to investigate the impact of hemodialysis on efficacies of the antiplatelet agents in coronary artery disease (CAD) patients complicated with end‑stage renal disease (ESRD).
Methods 86 CAD patients complicated with ESRD requiring hemodialysis were consecutively enrolled. After 5-day treatment with aspirin and clopidogrel or ticagrelor, the platelet aggregations induced by arachidonic acid (PLAA) or adenosine diphosphate (PLADP), and the P2Y12 reaction unit (PRU) were measured before and after hemodialysis. The propensity matching score method was adopted to generate a control group with normal renal function from 2439 CAD patients.
Results In patients taking aspirin, the PLAA remained unchanged after hemodialysis. In patients taking clopidogrel, the PLADP (37.26 ± 17.04 vs. 31.77 ± 16.09, p = 0.029) and corresponding clopidogrel resistance (CR) rate (23 [48.9%] vs.14 [29.8%], p = 0.022) significantly decreased after hemodialysis, though PRU remained unchanged. Subgroup analysis indicated that PLADP significantly decreased while using polysulfone membrane (36.8 ± 17.9 vs. 31.1 ± 14.5, p = 0.024). In patients taking ticagrelor, PLADP, and PRU remained unchanged after hemodialysis. ESRD patients had higher incidences of aspirin resistance (AR) and CR compared to those with normal renal function (AR: 16.1% vs. 0%, p = 0.001; CR: 48.4% vs. 24.8%, p = 0.024).
Conclusion Hemodialysis does not have negative effect on the efficacies of aspirin, clopidogrel and ticagrelor in ESRD patients with CAD. On the contrary, clopidogrel response may be improved while using the polysulfone membrane during hemodialysis. ESRD patients have higher incidences of AR and CR compared with those with normal renal function.
Trial registration ClinicalTrials.gov Identifier: NCT03330223.
Introduction
Sticky platelet syndrome is a less known platelet function disorder with a familiar occurrence and likely genetic background. Clinically, it is characterized by an increased risk of venous and arterial thromboembolic events and obstetric placenta-mediated complications. The increased aggregation after low-dose ADP and/or epinephrine is its distinctive laboratory feature. Though described for almost 40 years, several issues regarding its etiology, involved pathomechanisms, genetic background, optimal diagnostic and treatment approach remain controversial.
Areas covered
The work aims to summarize published studies, the actual definition of the syndrome, and point out its drawbacks. A literature search on Medline, Embase, and archives from EHA congresses was performed (terms: ‘sticky platelet syndrome’ - ‘platelet hyperreactivity’ - ‘platelet hyperaggregability’). The authors added in their unpublished data. The introductory overview of the present understanding is followed by the discussion of the pathophysiologic, diagnostic, and therapeutic problems.
Expert Opinion
Despite the growing evidence provided by case reports and series, the lack of robust studies limits the decision-making on diagnostics and management. The diagnostic issues, particularly the standardization of light transmission aggregometry, represent the crucial problem for the broader acceptance of the syndrome.
