Prevalence Of High On-treatment Platelet Reactivity Research Articles

Clopidogrel versus ticagrelor in the treatment of Chinese patients undergoing percutaneous coronary intervention: effects on platelet function assessed by platelet function tests and mean platelet volume

BackgroundKnowledge on the pharmacodynamic effects of antiplatelet drugs including clopidogrel and ticagrelor on Asian patients is scarce. We aim to evaluate the effects of the two drugs on platelet reactivity in the treatment of Chinese patients who underwent percutaneous coronary intervention (PCI), using two platelet function tests (PFT). Meanwhile, the relationship between mean platelet volume (MPV), a routine index of platelet size, and high on-treatment platelet reactivity (HPR) is also investigated.MethodsPatients receiving dual antiplatelet therapy (DAPT) were scheduled for the assessment of platelet reactivity at 2–3 days after PCI. Two PFTs, light transmission aggregometry (LTA) and vasodilator-stimulated phosphoprotein (VASP)-FCM assay, were applied in the evaluation of platelet reactivity. The MPV was measured simultaneously with EDTA plasma using a Sysmex XN 2000 automated hematology analyzer.ResultsThe final study population included the aspirin + clopidogrel group (n = 46) and the aspirin + ticagrelor group (n = 66). In the aspirin + ticagrelor group, the maximal light transmittance (LT) changes in response to 5 μM ADP assessed by LTA was obviously lower than that in the aspirin + clopidogrel group (P < 0.001). The platelet reactivity index (PRI) level in the VASP test was also markedly lower in the group given aspirin and ticagrelor (P < 0.001). There was a significant difference in HPR between the two groups. MPV showed a potent ability to predict the presence of HPR at VASP assay (AUC = 0.788, 95% CI: 0.701–0.875, P < 0.001) in receiver-operating characteristic curve analysis.ConclusionsCompared with clopidogrel, ticagrelor has dramatically greater antiplatelet effect, with a superiority in suppressing platelet function and a lower HPR rate. In addition, there existed a significant independent association between MPV and high prevalence of HPR in the VASP assay.

Platelet reactivity among patients with acute coronary syndromes and multivessel coronary artery disease

Abstract Background Patients with multivessel or complex coronary artery disease (CAD) are at increased risk of atherothrombotic events. It has been suggested that these patients may derive an incremental benefit with more intense antiplatelet strategies, according to prior subgroup analyses from randomized clinical trials. However, whether there is any association between the presence and extension of multivessel CAD and platelet aggregability (PA) in patients with acute coronary syndromes (ACS) is unknown. Purpose To analyze the independent association between PA and presence of multivessel CAD in patients with ACS. Methods Patients with ACS on dual antiplatelet therapy (aspirin plus clopidogrel) were included in this study. Multivessel CAD was defined as the presence of significant ≥50% stenosis at two or more major epicardic vessels. Platelet aggregability was assessed by VerifyNow P2Y12 assay expressed in P2Y12 Reactivity Units (PRU) on the day of discharge from the coronary care unit. High On-treatment platelet reactivity (HPR) was defined as PRU ≥208. Stepwise linear and logistic regression models were applied to adjust for confounders. Models were adjusted for: age, sex, race, diabetes, hypertension, smoking, dyslipidemia, prior MI, prior PCI, prior CABG, prior HF, prior stroke and ACS phenotype (STEMI vs. Non-ST-segment elevation ACS). Results A total of 237 patients were included, among whom 143 (60.3%) had multivessel CAD at the coronary angiogram and 175 (73.8%) were submitted to PCI during index hospitalization. Patients with multivessel disease were older (mean age 64.8±12.1 vs. 58.9±11.2 years; p&amp;lt;0.001) and more likely to have a history of diabetes (47.6% vs. 29.8%; p=0.006) and non-ST-segment elevation ACS as the index event (55.2% vs. 28.7%; p&amp;lt;0.001), compared to patients without multivessel CAD. After adjustments, presence of multivessel CAD was associated with higher PA (mean 161.4±74 PRU in patients with versus 140.3±70.9 PRU in patients without multivessel CAD; adjusted mean difference 23.7 PRU; 95% CI 4.8 to 42.5; p=0.014). Additionally, there was an incremental of 12.5 PRU (95% CI 2.8 to 22.3; adj p=0.012) for each diseased vessel and of 4.67 PRU (95% CI 0.11 to 9.22; adj p=0.045) for each diseased coronary segment. Compared to patients with single-vessel disease, patients with three-vessel disease had higher rates of HPR. (Figure). Conclusion In patients with ACS, the presence and extension of multivessel CAD were associated with higher levels of platelet aggregability and higher rates of high on-treatment platelet reactivity with clopidogrel. This finding may explain the incremental benefit with more intense antiplatelet therapies seen in this particular subgroup in prior clinical trials. Prevalence of HPR and extension of CAD Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Sao Paulo Research Foundation (FAPESP)

Association of clopidogrel high on-treatment reactivity with clinical outcomes and gene polymorphism in acute ischemic stroke patients

High on-treatment platelet reactivity (HTPR) was suggested to be better correlated with recurrent ischemic events as compared with gene polymorphism, whereas most of the results were from white populations with acute coronary disease. The evidence is relatively limited regarding HTPR and its genetic determinants in predicting clinical outcomes of stroke among Chinese-Han patients.A prospective study including 131 Chinese-Han stroke patients treated with clopidogrel was analyzed. Platelet function was assessed by light transmission aggregometry (LTA)- adenosine diphosphate (ADP) method. HTPR was defined as 5 μM ADP induced platelet aggregation > 46%. CYP2C19 and P2Y12 genotype were detected using the PCR-RFLP method. The difference in the occurrence of the primary endpoint was analyzed according to platelet function and genetic status.Sixty-three (48.1%) subjects displayed HTPR after administering clopidogrel for 1 week. The prevalence of HTPR was significantly higher in CYP2C19 loss-of-function (LOF) alleles (∗2, ∗3) carriers vs wild-type homozygotes (71.7% vs 32.1%, P < .01), and logistic regression analysis showed that carriers of CYP2C19 LOF alleles were an independent risk factor of HTPR. Survival analysis indicated that patients with HTPR had an increased risk of primary endpoints (20.6% vs 7.3%, P = .04), whereas the presence of CYP2C19 LOF alleles or P2Y12 H2 haplotype did not increase the incidence of ischemic events. Cox regression analysis demonstrated that HTPR was an independent predictor of the primary composite endpoint (HR, 3.1; 95% CI, 1.07–8.99; P = .04).We identified a high prevalence of clopidogrel-HTPR in a cohort of Chinese-Han patients with acute ischemic stroke, and patients with HTPR may have an increased risk of recurrent ischemic stroke events. CYP2C19 LOF alleles are associated with HTPR but not with stroke prognosis. Further clinical trials with large samples are needed to confirm these findings.

Increased platelet reactivity after heart transplantation

BackgroundThe role of antiplatelet therapy following heart transplantation (HT) is unclear. Ex-vivo studies suggest increased platelet hyperaggregability after HT. Recent studies suggest that early aspirin therapy is associated with improved survival and lower rates of cardiac allograft vasculopathy (CAV). We examined: (1) the prevalence of increased platelet reactivity on aspirin and clopidogrel post-HT, (2) platelet reactivity post-clopidogrel treatment in aspirin-resistant patients, and (3) the relationship between platelet reactivity and outcomes. MethodsHT patients on aspirin and/or clopidogrel who underwent coronary angiography in 2015–2018 were assessed using the VerifyNow aspirin and/or P2Y12 assay. High on-treatment platelet reactivity (HPR) to aspirin and clopidogrel were defined by aspirin reaction unit (ARU) > 550 and P2Y12 reaction unit (PRU) > 208. Patients with HPR to aspirin were switched to clopidogrel for 7 days, then reassessed with the P2Y12 assay. ResultsPlatelet reactivity was assessed in 76 patients at 4.6 (IQR 2.2-9.4) median years post-HT. ARU was assessed in 71 patients and PRU in 16 patients. Median ARU was 471 (IQR 419-537) and PRU 186 (IQR 120-244). The prevalence of HPR to aspirin and clopidogrel were 18% and 37%, respectively, which is comparable to patients with coronary artery disease. 45% of patients with HPR to aspirin also had HPR to clopidogrel. There was no difference in aspirin HPR prevalence between patients with and without CAV. ConclusionsThere is increased platelet reactivity despite treatment with aspirin or clopidogrel following HT. Further evaluation may determine whether increased platelet reactivity is associated with adverse outcomes including the development of CAV.

P6405Potential for drug-drug interaction between vonoprazan and prasugrel on antiplatelet effect assessed by VerifyNow P2Y12 assay in patients with coronary artery disease

Abstract Background Vonoprazan is a potassium-competitive acid blocker increasingly used in Japan to prevent gastrointestinal bleeding in patients under dual antiplatelet therapy (DAPT) after coronary stents implantation. Since cytochrome P450 (CYP) 3A4 is involved in the primary metabolism of vonoprazan and prasugurel, there is a possibility that CYP-mediated drug-drug interaction between them can attenuate the antiplatelet function of prasugrel. Purpose The aim of this study was to investigate whether antiplatelet effect of prasugrel could be attenuated upon coadministration with vonoprazan compared to conventional proton pump inhibitors (PPIs). Method We evaluated 72 patients (57 males, 67±11 years) with coronary artery disease who were taking either vonoprazan (n=35) or PPIs (n=37) in combination with DAPT (aspirin and prasugrel) after drug-eluting stents implantation. PPIs included 21 esomeprazole, 8 lansoprazole, and 8 rabeprazole. Antiplatelet effects of prasugrel were assessed using VerifyNow P2Y12 assay. Primary measurements were P2Y12 reaction units (PRU) and P2Y12 percent inhibition. High on-treatment platelet reactivity (HPR) on prasugrel was defined as PRU &gt;208. Administration period of vonoprazan or PPIs in combination with DAPT ≤7 days was defined as early administration period. Results Median administration period of vonoprazan or PPIs in combination with DAPT was 127 days. There were no significant differences in baseline clinical characteristics between patients with vonoprazan and PPIs. In the analysis for all subjects, patients with vonoprazan showed similar PRU (166±50 vs. 167±64, p=0.93) and percent inhibition (36±18 vs. 38±23, p=0.66) compared to those with PPIs. No significant differences were observed in the prevalence of HPR between patients with vonoprazan and PPIs (17 vs. 30%, p=0.27). In the analysis for patients in early administration period [vonoprazan (n=14) vs. PPIs (n=10)], there were no significant differences in PRU (166±47 vs. 186±82, p=0.45), percent inhibition (33±17 vs. 30±26, p=0.73), and prevalence of HPR (14 vs. 50%, p=0.085) between patients with vonoprazan and PPIs. In addition, the analysis for patients over early administration period [vonoprazan (n=21) vs. PPIs (n=27)] showed that PRU (166±55 vs. 160±57, p=0.73), percent inhibition (37±19 vs. 41±21, p=0.57), and prevalence of HPR (19 vs. 22%, p=1.00) were comparable between patients with vonoprazan and PPIs. Conclusion Compared to PPIs, vonoprazan did not exhibit significant inhibitory effects on the antiplatelet activity of prasugrel assessed by VerifyNow assay. These findings suggest that there are possibly no clinically harmful drug-drug interactions between vonoprazan and prasugrel.

Prevalence of clOpidogrel ‘resIstaNce’ in a selected population of patients undergoing elective percutaneous coronary intervention at a tertiary cardiovascular centre in Trinidad: the POINT pilot study

Objectives This novel, pilot study aimed to assess the estimated prevalence of high on-treatment platelet reactivity (HPR) in Trinidad and Tobago.MethodsPatients (n=40) who were awaiting elective percutaneous coronary intervention on...

Prevalence and predictors of high-on treatment platelet reactivity during prasugrel treatment in patients with acute coronary syndrome undergoing stent implantation

BackgroundADP-antagonists such as prasugrel have reduced but yet not overcome the phenomenon of high-on treatment platelet reactivity (HRPR), that has been shown to increase the rate of major cardiovascular events after an acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI). However, the exact prevalence and the principal determinants of suboptimal platelet inhibition in patients treated with dual antiplatelet therapy (DAPT) with prasugrel have not been completely clarified and were therefore the aim of the present study. MethodsWe included patients (<75 years and >60kg) treated with DAPT (aspirin+prasugrel) after PCI, mainly for an ACS. Platelet function test evaluation was performed at 1–3 months from discharge. HRPR was assessed by multiplate impedance aggregometry and defined for results above upper limit of normal after ADP stimulation. ResultsWe included 190 post-ACS patients. HRPR with prasugrel was observed in 19 patients (10%). The prevalence of HRPR was stable in different high-risk subgroups of patients (female gender, hypercholesterolemic, and chronic kidney disease) whereas it was increased in diabetic patients (p=0.045), with a significant interaction between diabetic status and HRPR (p=0.04). However, at multivariate analysis, an impaired metabolic status, with higher levels of glycosylated hemoglobin and low-density lipoprotein (LDL) cholesterol, but not diabetic status, emerged as independent predictors of HRPR with prasugrel [OR (95% CI)=2.1 (1.32–3.33), p=0.002 and OR (95% CI)=1.03 (1.01–1.05), p=0.003, respectively], with a stronger linear relationship between ADP-mediated platelet aggregation and glycosylated hemoglobin levels (r=0.24, p=0.002), than for LDL-cholesterol (r=0.13, p=0.09). ConclusionsIn post-ACS patients treated with PCI and receiving DAPT with prasugrel, HRPR is observed in about 10% of patients. Impaired metabolic status, and especially elevated glycosylated hemoglobin, emerged as independent predictors of the suboptimal effectiveness of prasugrel.

Impact of Point-of-Care Platelet Function Testing Among Patients With and Without Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents (from the ADAPT-DES Study)

We sought to examine if the risk conferred by high on-treatment platelet reactivity (HPR) varies based upon clinical presentation. We examined the relation between HPR (P2Y12 reaction units >208) and adverse ischemic and bleeding events among patients with and without acute coronary syndromes (ACS) from ADAPT-DES; 51.7% of patients had ACS. After clopidogrel loading, ACS patients had higher P2Y12 reaction units and a greater prevalence of HPR based on VerifyNow P2Y12 assay. Of 92 definite or probable stent thrombosis (ST) events at 2 years, 65.2% occurred among patients with ACS. HPR was independently associated with ST in ACS patients (adjusted hazard ratio 2.29, 95% confidence interval 1.32 to 3.98) but not with clinically relevant bleeding. Although no statistical interactions between ACS status and these associations were observed, non-ACS patients exhibited an attenuated association between HPR and ST, and an inverse association between HPR and clinically relevant bleeding. HPR was similarly associated with myocardial infarction, but not with overall mortality in ACS and non-ACS patients. In conclusion, the majority of ST events in the 2 years after drug-eluting stent placement occurred in ACS patients; HPR was strongly associated with ST in these patients. These data support current recommendations for using more potent antiplatelet therapies in ACS patients.

Impact of immature platelet fraction on platelet reactivity during prasugrel maintenance treatment

Residual high on-treatment platelet reactivity (HTPR) despite dual antiplatelet therapy (DAPT) has emerged as a predictor of major ischemic events in patients undergoing percutaneous coronary interventions (PCIs), especially after an acute cardiovascular event. However, its determinants are still poorly defined. Therefore, the aim of the present study was to evaluate the role of the percentage of reticulated platelets on HTPR in patients on DAPT with ASA (100–160 mg) and prasugrel (10 mg).Platelet reactivity and the reticulated platelets fraction (immature platelets fraction [IPF]) were assessed at 30–90 days after an acute coronary syndrome. Aggregation was assessed by multiple-electrode aggregometry. HTPR was defined as ADP test > 417 AU × min.Our population is represented by 180 ACS patients undergoing stent implantation, divided according to median values of IPF (< or ≥ 2.8%). Higher IPF values were associated to lower platelet count (p < 0.001) and a higher rate of active smokers (p = 0.02). No difference was observed in terms of mean platelet reactivity, with different activating stimuli. The prevalence of HTPR on prasugrel did not significantly differ in patients with IPF < or ≥ 2.8% (8%vs. 11.8%, p = 0.46; adjusted OR [95% CI] = 1.89 [0.66–5.4], p = 0.24).Our study showed that in patients treated with prasugrel after PCI for ACS, the immature platelet fraction influences neither platelet reactivity nor the rate of HTPR.

Prevalence of high on-treatment platelet reactivity in patients with chronic kidney disease treated with acetylsalicylic acid for stroke prevention.

Introduction Chronic kidney disease (CKD) is one of risk factors for stroke and may be associated with impaired platelet reactivity. Objectives The aim of the study was to evaluate platelet reactivity in patients with CKD treated with acetylsalicylic acid (ASA), using 2 different laboratory methods. Moreover, we searched for factors responsible for the phenomenon of high on-treatment platelet reactivity (HOPR). Patients and methods A total of 108 patients with CKD and 41 controls without CKD using ASA were enrolled in the study. Platelet function was assessed by impedance aggregometry in whole blood, using a multi-channel platelet function analyzer (Multiplate®; ASPItest). Urinary 11-dehydrotromboxane levels were measured by the AspirinWorks® test. Results No significant differences were observed in the prevalence of HOPR between patients with and without CKD. Patients with CKD and HOPR measured by ASPItest had higher creatinine levels (P = 0.05) and were younger (P <0.01) than patients with CKD without HOPR, while patients with CKD and HOPR measured by AspirinWorks® had lower red blood cell count (P = 0.05), hemoglobin (P = 0.05), hematocrit (P = 0.05), and high-density lipoprotein levels (P = 0.05). All patients with HOPR had higher C-reactive protein levels (P <0.05) (AspirinWorks®) and white blood cells (P <0.05) (ASPItest). Conclusions The applied methods allowed to detect HOPR in more than one third of CKD patients taking ASA for stroke prevention. The compatibility of both methods for HOPR assessment was confirmed. The study revealed several potential risk factors for HOPR in CKD, including younger age, higher levels of inflammatory markers, dyslipidemia, and lower hematocrit and hemoglobin levels.

Efficacy of 2.5-mg Prasugrel in Elderly or Low-Body-Weight Patients.

Due to concern about bleeding complications, a maintenance dose of prasugrel 2.5 mg may be used in elderly or low-body-weight patients in Japan. There is little information, however, on the efficacy and safety of a 2.5-mg maintenance dose of prasugrel. Methods and Results: In this single-center, prospective, open-label, cross-over study, a total of 44 elderly (≥75 years old) or low body-weight (<50 kg) Japanese patients >1 month after percutaneous coronary intervention who were treated with aspirin 81-100 mg and clopidogrel 75 mg were randomized to either prasugrel 2.5 mg or 3.75 mg instead of clopidogrel for 14 days, with a cross-over directly to the alternate treatment for another 14 days. Platelet inhibition was assessed with the VerifyNow assay (Accumetrics, San Diego, CA, USA) at 3 time points: baseline; day 14; and day 28. P2Y12 reaction units (PRU) ≤95 was defined as low on-treatment platelet reactivity (LPR), and PRU ≥262 as high on-treatment platelet reactivity (HPR). The prevalence of LPR was 2.2% in patients treated with clopidogrel, 2.2% in those with prasugrel 2.5 mg, and 22.7% in those with prasugrel 3.75 mg (P<0.001). Clopidogrel resulted in the higher prevalence of HPR compared with 2.5-mg and 3.75-mg prasugrel (40.9% vs. 18.2% vs. 6.8%, P<0.001). Prasugrel 2.5 mg may be more appropriate in elderly or lower-body-weight Japanese patients.

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study.

BackgroundThere is a link between high on-treatment platelet reactivity (HPR) and adverse vascular events in stroke. This study aimed to compare multiple electrode platelet aggregometry (MEA), in healthy subjects and ischaemic stroke patients, and between patients naive to antiplatelet drugs (AP) and those on regular low dose AP. We also aimed to determine prevalence of HPR at baseline and at 3–5 days after loading doses of aspirin.MethodsPatients with first ever ischaemic stroke were age and sex-matched to a healthy control group. Three venous blood samples were collected: on admission before any treatment given (baseline); at 24 h and 3–5 days after standard treatment. MEA was determined using a Mutliplate® analyser and agonists tested were arachidonic acid (ASPI), adenosine diphosphate (ADP) and collagen (COL).ResultsSeventy patients (mean age 73 years [SD 13]; 42 men, 28 women) were age and sex-matched to 72 healthy subjects. Thirty-three patients were on antiplatelet drugs (AP) prior to stroke onset and 37 were AP-naive. MEA results for all agonists were significantly increased in AP-naive patients compared to healthy subjects: ADP 98 ± 31 vs 81 ± 24, p < 0.005; ASPI 117 ± 31 vs 98 ± 27, p < 0.005; COL 100 ± 25 vs 82 ± 20, p < 0.005. For patients on long term AP, 33% (10/30) of patients were considered aspirin-resistant. At 3–5 days following loading doses of aspirin, only 11.1% were aspirin resistant based on an ASPI cut-off value of 40 AU*min.ConclusionsMany patients receiving low dose aspirin met the criteria of aspirin resistance but this was much lower at 3–5 days following loading doses of aspirin. Future studies are needed to establish the causes of HPR and potential benefits of individualizing AP treatment based on platelet function testing.

Platelet reactivity in patients undergoing transcatheter aortic valve implantation.

Thromboembolic events, primarily stroke, might complicate transcatheter aortic-valve implantation (TAVI) procedures in 3-5% of cases. Thus, it is common to administer aspirin and clopidogrel pharmacotherapy for 3-6months following TAVI in order to prevent those events. The biologic response to the dual anti platelet treatment (DAPT) is heterogeneous, e.g. low response, known as high on treatment platelet reactivity (HTPR) may be associated with adverse thromboembolic events. Little is known about the prevalence of HTPR among patients undergoing TAVI. To assess the variability in response and rates of residual platelet reactivity in patients undergoing TAVI. We examined platelet reactivity in response to clopidogrel and aspirin in 40 consecutive patients (mean age 81.7±6.5years, 66.7% women) who underwent successful TAVI using the VerifyNow P2Y12 assay and the multiple electrode aggregometry assay (Multiplate analyzer) in response to adenosine diphosphate and arachidonic acid respectively, at different time points before and following TAVI. Before TAVI, the majority of patients were on antiplatelet therapy (68.5% aspirin, 12.5% clopidogrel, 12.5% DAPT). Following the procedure all patients were on DAPT or clopidogrel and warfarin. Among analyzed patients, 41% had HTPR for clopidogrel and 12.5% for aspirin at baseline, which did not significantly change 1-month following the procedure (p=0.81 and p=0.33, respectively). In conclusion, patients undergoing TAVI for severe aortic stenosis and treated with DAPT have high rates of residual platelet reactivity during the peri-procedural period and up to 1-month thereafter. These findings may have clinical implications for the anti-platelet management of TAVI patients.

Platelet Larger Cell Ratio and High-on Treatment Platelet Reactivity During Dual Antiplatelet Therapy

Low response to antiplatelet agents has been associated to an increased risk of thrombotic complications and recurrent ischemic events. Platelet size has been proposed as a potential marker of platelet reactivity. Therefore, the aim of the present study was to evaluate the impact of platelet Larger Cell Ratio (p-LCR) on platelet aggregation and the prevalence of residual high-on treatment platelet reactivity (HRPR) in patients receiving dual antiplatelet therapy (DAPT) after a recent acute coronary syndrome or coronary revascularization. Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30-90 days post-discharge. HRPR was considered for ASPI test >862 AU*min (for ASA) or ADP test values ≥417 AU*min (for ADP-antagonists) using impedance aggregometry. Our population consisted of 530 patients receiving DAPT, who were divided in tertiles according to values of p-LCR (< 27.6; 27.6-34.7; ≥34.7 l). p-LCR was related with use of beta-blockers (p = 0.02) and statins (p = 0.002), and inversely with acute presentation (p = 0.05). Higher platelet count (p < 0.001) and haemoglobin levels (p = 0.001) were observed in higher p-LCR tertiles. The prevalence of HRPR for ASA was low and not significantly different across tertiles of p-LCR (1.1 vs 1.1 vs 1.7%, p = 0.66; adjusted OR[95%CI] = 1.68[0.66-4.29], p = 0.27). Moreover, p-LCR did not influence the occurrence of HRPR for ADP-antagonists (24.4% vs 20.9% vs 25.6 %%, p = 0.80, adjusted OR[95%CI] = 0.88[0.67-1.17], p = 0.38) and similar results were obtained when considering separately patients receiving clopidogrel (adjusted OR[95%CI] = 1.21[0.86-1.69], p = 0.29) or ticagrelor (adjusted OR[95%CI] = 1.17[0.69-2], p = 0.56). In patients receiving DAPT for coronary artery disease, p-LCR does not impact platelet reactivity. Larger platelets did not influence the prevalence of high-on treatment platelet reactivity with the antiplatelet agents ASA, clopidogrel or ticagrelor.

The relationship between on-clopidogrel platelet reactivity, genotype, and post-percutaneous coronary intervention outcomes in Chinese patients

Background. High on-clopidogrel platelet reactivity reflects a poor response to clopidogrel and is associated with ischemic events, which has been attributed to several factors such as demographic, clinical characteristics and a polymorphism of CYP2C19. Some new platelet assays monitoring on-clopidogrel platelet reactivity are currently available in China, but their relevance to the CYP2C19 genotype and post-percutaneous coronary intervention outcomes remain to be elucidated. Methods. Patients were prospectively included if they had a successful percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and received clopidogrel and aspirin. CYP2C19 loss-of function genotype, adenosine diphosphate (ADP)-induced maximum platelet aggregation rate (MPAADP) measured by light transmittance aggregometry, ADP-induced platelet-fibrin clot strength (MAADP) measured by thrombelastography, platelet reactivity index (PRI) measured by vasodilator-stimulated phosphoprotein phosphorylation (VASP), and the occurrence of 6-month major adverse cardiovascular events (MACE) were assessed in 178 patients. Results. High on-treatment platelet reactivity prevalence defined by MPAADP > 46.0%, MAADP > 47 mm and PRI > 50.0% was 27.0%, 24.2%, and 61.2%, respectively. ADP-specific assays (VASP PRI) differed according to CYP2C19 genotype, with a significant gene–dose effect (PMs > IMs > EMs, p < 0.05). Multivariate analysis showed MPAADP > 46.0% and MAADP > 47 mm to be independent predictors of MACE at 6 months. Conclusions. CYP2C19 loss-of function genotypes with the *2 and/or *3 allele are highly prevalent in the Chinese population and are associated with higher residual platelet reactivity. High on-treatment platelet reactivity defined by MPAADP or MAADP predicts an increased risk of MACE for ACS patients undergoing PCI.

Abstract 18307: Prevalence, Predictors and Prognostic Impact of High On-treatment Platelet Reactivity to Aspirin and Clopidogrel in Patients With Symptomatic Peripheral Artery Disease in Japanese Population

Introduction: High on-treatment platelet reactivity (HPR) is associated with increased risk of ischemic events and therapeutic failure in patients with coronary artery disease, whereas its role in patients with peripheral artery disease is not widely reported. Purpose: This study aims to investigate the prevalence of HPR in patients with symptomatic peripheral artery disease and its possible predictors in Asian population. Methods: Among patients who underwent endovascular therapy at our institution during September 2013 to April 2014, 125 patients who received aspirin and/or clopidogrel were included. Residual platelet reactivity was assessed with VerifyNow aspirin and P2Y12 assays. HPR was defined as aspirin reaction units (ARU) ≧ 550 for aspirin and P2Y12 reaction units (PRU) ≧ 235 for clopidogrel. Results: The prevalence of HPR to aspirin was not significantly different between patients with intermittent claudication (IMC) and critical limb ischemia patients (22.2% and 23.2%, respectively), whereas the prevalence of HPR to clopidogrel was higher in CLI patients, especially in patients with tissue loss compared to IMC patients (39.3% and 62.5%, respectively, p&lt;0.05). 7.7% of IMC patients and 12.5% of CLI patients showed HPR to both aspirin and clopidogrel. Multivariate analysis revealed that age and diabetes were independent predictors for HPR to clopidogrel. Conclusion: HPR to aspirin and/or clopidogrel was highly prevalent in symptomatic PAD patients in Japanese population. The prevalence of HPR was significantly higher in patients with tissue loss compared with those without. Optimizing antiplatelet regimen according to residual platelet reactivity in CLI patients would be indispensable to avoid repeat revascularization and unexpected amputation.

Prevalence of High On-treatment Platelet Reactivity in Diabetic Patients Treated with Aspirin

BackgroundRandomized controlled trials have shown that ≤100 mg aspirin daily is not effective for primary prevention of cardiovascular events in diabetes; however, clinical and pharmacologic evidence suggests these patients need >100 mg for adequate antiplatelet activity. Although high on-treatment platelet reactivity (HTPR) could explain the lack of benefit, prevalence of HTPR in diabetes is not known. This systematic review examined the relationship between daily aspirin dose and prevalence of HTPR in patients with diabetes. MethodsThree electronic databases were searched until May 2013 using database-appropriate terms for aspirin, resistance, and diabetes. Studies were included if prevalence of HTPR was reported according to daily dose and diabetes status. Patients were stratified by daily aspirin dose and the weighted mean prevalence across studies was calculated. Where appropriate, pooled relative risks (RR) were calculated using a random-effects model. ResultsData were available from 31 studies that enrolled 2147 diabetic patients. Overall, prevalence of HTPR was 21.9% (95% confidence interval [CI], 15.2%-28.5%) in diabetic patients and 15.8% (95% CI, 11.4%-20.3%) in nondiabetic patients (pooled RR 1.36; 95% CI, 1.08-1.71; I2 56%). Prevalence appeared to be dose related, with 398 (23.6%) of 1689 diabetic patients using ≤100 mg daily having HTPR compared with 64 (12.3%) of 518 diabetic patients using 101-325 mg daily (pooled RR 1.70; 95% CI, 1.07-2.72; I2 0%). ConclusionsAlthough these observations should be verified in a clinical trial, the possibility that 1 in 4 patients have HTPR with doses commonly used in diabetes could have significant implications on overall effectiveness of aspirin.

ASSA13-15-1 Clinical Characteristics Related with High On-Treatment Platelet Reactivity Receiving Clopidogrel Measured by Thrombelastography in Patients Undergoing Percutaneous Coronary Intervention

Background an Objective Antiplatelet therapy with clopidogrel and aspirin is the current standard of care for patients undergoing PCI. However, recurrent ischemic event occurrence during dual antiplatelet therapy, including stent thrombosis, remains a major concern. We sought to determine whether clinical characteristics will be associated with high on-treatment platelet reactivity receiving clopidogrel measured by thrombelastography. Methods A total of 362 consecutive patients undergoing non-emergent PCI were enrolled in this prospective observational study. A 300mg clopidogrel loading dose was administered on the day before procedure ( > 12h). Blood samples were analysed using a computerised TEG analyser for platelet aggregation. The cut points for high on-treatment platelet reactivity (HPR) were defined as ≥60% ADP-induced aggregation with 2-μmol ADP. All patients below the cut point were defined as exhibiting normal on-treatment platelet reactivity (NPR). Results The prevalence of HPR was 33% measured by TEG. There were more female (41.7% vs 22.3%, P = 0.007), more diabetes mellitus (41.7% vs 24.2%, P = 0.0024) and more smoking patients (12.3% vs 2.6%, P = 0.012) in HPR group than in NPR group, respectively. Meanwhile, elevated plasma triglyceride was common in HPR group than in NPR group (2.5 ± 0.9mmol/L vs 1.9 ± 0.3mmol/L, P = 0.019). Patients with HPR exhibited a higher level of cardiac enzyme including CK-MB (3.1 ± 1.3ng/mL vs 1.8 ± 1.6ng/mL, P = 0.013) and troponin I (0.9 ± 0.3ng/mL vs 0.2 ± 0.4ng/mL, P = 0.01). Conclusions Despite adequate pretreatment with clopidogrel, 33% patients undergoing non-emergent PCI exhibited high on-treatment ADP-induced platelet aggregation measured by thrombelastography. We found that current smoking, high level of HbA1C and TnI, and female gender independently predicted the risk of HPR.

Decrease in high on-treatment platelet reactivity (HPR) prevalence on switching from clopidogrel to prasugrel: Insights from the switching anti-platelet (SWAP) study

The prevalence of high platelet reactivity (HPR) in patients who have switched from clopidogrel to prasugrel during maintenance phase after an acute coronary syndrome (ACS) event is unknown. Therefore, the effect of switching from clopidogrel to prasugrel on the prevalence of HPR was evaluated. This analysis from the previously reported SWAP (SWitching Anti Platelet) study assessed HPR at baseline, 2 and 24 hours, and seven days after switching from clopidogrel to prasugrel maintenance dose (MD), with or without a prasugrel loading dose (LD) using four definitions: maximum platelet aggregation (MPA) >65% (primary endpoint), MPA >50%, P2Y12 reaction units (PRU) >235, and platelet reactivity index (PRI) ≥ 50%. A total of 95 patients were available for analysis; 56 patients provided DNA for genetic assessments of cytochrome P450 (CYP) 2C19. There were 26 (27.4%) patients with HPR at the end of the clopidogrel run-in (defined as MPA >65%). The HPR prevalence varied by each definition and ranged from 19% (PRU >235) to 68% (PRI ≥ 50 %). A significantly higher HPR prevalence was observed during clopidogrel versus the combined prasugrel therapy groups at seven days as measured by MPA >65% (21.2% vs. 4.5%, p<0.05), PRU >235 (18.8% vs. 0%, p=0.001), and PRI ≥ 50 % (66.7% vs. 7.9%, p<0.0001). There was a significantly higher percentage of subjects carrying at least one reduced function allele with HPR measured by MPA >65% (p=0.02) or PRU >235 (p=0.05) than non-carriers with HPR. Switching ACS patients during maintenance clopidogrel therapy to prasugrel with or without an LD is associated with a reduced HPR prevalence and may provide an alternative strategy to treat patients with HPR, independent of CYP2C19 genotype.

Clinical characteristics associated with high on-treatment platelet reactivity of patients undergoing PCI after a 300 mg loading dose of clopidogrel, measured by thrombelastography

BackgroundDual antiplatelet therapy with clopidogrel and aspirin is the standard of care for patients undergoing percutaneous coronary intervention (PCI).ObjectiveTo determine the clinical characteristics associated with high on-treatment platelet reactivity (HPR)...