PON1 Q192R is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: A prospective single-center cohort study

Background and purpose The impact of the paraoxonase-1 (PON1) polymorphism, Q192R, on platelet inhibition in response to clopidogrel remains controversial. We aimed to investigate the association between carrier status of PON1 Q192R and high platelet reactivity (HPR) with clopidogrel in patients undergoing elective neurointervention. Methods Post-clopidogrel platelet reactivity was measured using a VerifyNow® P2Y12 assay in P2Y12 reaction units (PRU) for consecutive patients before the treatment. Genotype testing was performed for PON1 Q192R and CYP2C19*2 and *3 (no function alleles), and *17. PRU was corrected on the basis of hematocrit. We investigated associations between factors including carrying ≥1 PON1 192R allele and HPR defined as original and corrected PRU ≥208. Results Of 475 patients (232 men, median age, 68 years), HPR by original and corrected PRU was observed in 259 and 199 patients (54.5% and 41.9%), respectively. Carriers of ≥1 PON1 192R allele more frequently had HPR by original and corrected PRU compared with non-carriers (91.5% vs 85.2%, P = 0.031 and 92.5% vs 85.9%, P = 0.026, respectively). In multivariate analyses, carrying ≥1 PON1 192R allele was associated with HPR by original (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.03–3.76) and corrected PRU (OR 2.34, 95% CI 1.21–4.74) after adjustment for age, sex, treatment with antihypertensive medications, hematocrit, platelet count, total cholesterol, and carrying ≥1 CYP2C19 no function allele. Conclusions Carrying ≥1 PON1 192R allele is associated with HPR by original and corrected PRU with clopidogrel in patients undergoing elective neurointervention, although alternative results related to other genetic polymorphisms cannot be excluded.

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Comparison of methods to evaluate clopidogrel-mediated platelet inhibition after percutaneous intervention with stent implantation

Thrombosis and Haemostasis ◽

10.1160/th08-09-0577 ◽

2009 ◽

Vol 101 (02) ◽

pp. 333-339 ◽

Cited By ~ 83

Author(s):

Sabine Steiner ◽

Daniela Seidinger ◽

Renate Koppensteiner ◽

Thomas Gremmel ◽

Simon Panzer ◽

...

Keyword(s):

Stent Implantation ◽

Light Transmission ◽

Platelet Reactivity ◽

Platelet Inhibition ◽

Percutaneous Intervention ◽

Adverse Outcomes ◽

Gold Standard Method ◽

Platelet Aggregometry ◽

Increased Risk ◽

The Impact

SummaryA high on-treatment residual ADP-inducible platelet reactivity in light transmission aggregometry (LTA) has been associated with an increased risk of adverse outcomes after percutaneous coronary intervention (PCI). However, LTA is weakly standardized, and results obtained in one laboratory may not be comparable to those obtained in another one. We therefore sought to determine the test correlating best with LTA to estimate clopidogrel-mediated platelet inhibition in 80 patients on dual antiplatelet therapy after elective percutaneous intervention with stent implantation. We selected the VerifyNow P2Y12 assay, the vasodilator-stimulated phosphoprotein phosphorylation assay, multiple electrode platelet aggregometry and the Impact-R for comparisons with LTA. Cut-off values for residual ADP-inducible platelet reactivity were defined according to quartiles of each assay. Sensitivities and specificities of the different platelet function tests were based on the results from LTA. The results from all four assays correlated significantly with those from LTA. The VerifyNow P2Y12 assay revealed the strongest correlation (r = 0.61, p < 0.001). Sensitivities and specificities ranged from 35% to 55%, and from 78.3% to 85%, respectively. In conclusion, although all assays correlated significantly with LTA, they need to be improved to become clinically used diagnostic tests. Further, it may be too early to define the gold standard method for assessing residual ADP-inducible platelet reactivity and generally acceptable cut-off values.

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Effect of bodyweight on VerifyNow Aspirin platelet function test: a retrospective review

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2020-016842 ◽

2020 ◽

pp. neurintsurg-2020-016842

Author(s):

Melissa Sandler ◽

Cuong Hoang ◽

Hannah Y Mak ◽

Michael R Levitt

Keyword(s):

Stent Thrombosis ◽

Retrospective Review ◽

Platelet Reactivity ◽

Thrombotic Event ◽

Optimal Dose ◽

Platelet Inhibition ◽

Platelet Function Test ◽

Assay Result ◽

The Mean ◽

The Impact

BackgroundAntiplatelet therapy is used to prevent stent thrombosis in intracranial stents, but the optimal dose of aspirin is unknown. This study sought to determine whether the degree of platelet inhibition with aspirin is affected by bodyweight as observed through a platelet reactivity assay.MethodsThis is a retrospective review of patients who underwent neurovascular stent placement and had a VerifyNow Aspirin assay result. The primary outcome was the correlation between the VerifyNow Aspirin result, bodyweight, and the initial dose of aspirin. Secondary outcomes included the impact of the VerifyNow P2Y12 result and of weight on the incidence of bleeding or a thrombotic event.ResultsOf the 142 included patients, 62.7% weighed ≥70 kg and 88.7% were initiated on aspirin 300–325 mg daily. 83.8% achieved a therapeutic VerifyNow Aspirin result. There was minimal correlation between the VerifyNow Aspirin result, bodyweight, and aspirin dose (R2=0.02). Between patients who weighed <70 kg versus ≥70 kg, there was no difference in the mean aspirin reaction units (ARU) (449 vs 435, p=0.32) or in the incidence of bleeding (28% vs 17.1%, p=0.14) or a thrombotic event (4% vs 5.3%, p=0.59). No patient experienced stent thrombosis and eight patients experienced in-stent stenosis. In a multivariate analysis, only the VerifyNow P2Y12 result predicted the development of either bleeding or a thrombotic event (p<0.01).ConclusionsBodyweight did not influence the likelihood of obtaining a therapeutic VerifyNow Aspirin result. The clinical utility of obtaining VerifyNow Aspirin assays for this patient population is unknown.

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Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways

Thrombosis and Haemostasis ◽

10.1160/th13-03-0263 ◽

2013 ◽

Vol 110 (12) ◽

pp. 1223-1231 ◽

Cited By ~ 11

Author(s):

Dominick J. Angiolillo ◽

Jose L. Ferreiro ◽

Joseph A. Jakubowski ◽

Kenneth J. Winters ◽

Mark B. Effron ◽

...

Keyword(s):

Genetic Variants ◽

Active Metabolite ◽

Platelet Reactivity ◽

Coronary Intervention ◽

Platelet Inhibition ◽

Reactivity Index ◽

Coronary Syndrome ◽

Metabolite Generation ◽

Artery Disease ◽

The Impact

SummaryClopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers; extensive metabolisers [EM] = *1/1 homozygotes; reduced metabolisers [RM] = *2 carriers). ABCB1 T/T and C/T polymorphisms and PON1 A/A, A/G and G/G polymorphisms were also genotyped. PD parameters were assessed using VerifyNow® P2Y12 and vasodilator stimulated phosphoprotein (VASP) expressed as platelet reactivity index (PRI) after 14 days of maintenance dosing. Clopidogrel and prasugrel active metabolite (AM) exposure was calculated in a cohort of 96 patients. For clopidogrel, genetic variants in CYP2C19, but not ABCB1 or PON1, affected PK and PD. For prasugrel, none of the measured genetic variants affected PK or PD. Compared with clopidogrel, platelet inhibition with prasugrel was greater even in the CYP2C19 UM phenotype. Prasugrel generated more AM and achieved greater platelet inhibition than clopidogrel irrespective of CYP2C19, ABCB1, and PON1 polymorphisms. The lack of effect from genetic variants on prasugrel AM generation or antiplatelet activity is consistent with previous studies in healthy volunteers and is consistent with improved efficacy in acute coronary syndrome patients managed with percutaneous coronary intervention.

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Abstract WP116: Association Between Smoking Status, Platelet Function and Clinical Outcomes of Ticagrelor versus Clopidogrel in Patients With Minor Stroke or Transient Ischemic Attack

Stroke ◽

10.1161/str.51.suppl_1.wp116 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Yingying Yang ◽

Yilong Wang

Keyword(s):

Clinical Outcomes ◽

Platelet Function ◽

Platelet Reactivity ◽

Smoking Status ◽

Minor Stroke ◽

Carrier Status ◽

Bleeding Events ◽

Vascular Events ◽

Treatment Groups ◽

The Impact

Background: Association between smoking status, platelet function and clinical outcomes of ticagrelor versus clopidogrel in patients with minor stroke or transient ischemic stroke (TIA) remains unclear. Methods: A subgroup analysis was conducted of Platelet Reactivity in Acute Non-disabling Cerebrovascular Events (PRINCE) trial. PRINCE trial was a randomized, prospective, multicenter, open-label, active-controlled, and blind-endpoint trial, which randomized patients with acute minor stroke, or TIA, to ticagrelor plus aspirin or clopidogrel plus aspirin within 24 hours of symptoms onset. Patients who smoked at least one cigarette per day for at least one year in their lives were defined as smokers. Platelet reactivity was assessed by the VerifyNow P2Y12 assay at baseline, 7+2 days and 90±7 days. High-on-treatment platelet reactivity (HOPR) was defined as P2Y12 reaction units >208.Clinical outcomes included any stroke, composite clinical vascular events and bleeding events at 90 days. Results: Among 675 patients enrolled in the PRINCE trial, 370 patients (54.8%) were smokers. At 7+2 days, the proportion of HOPR in ticagrelor versus clopidogrel was significantly lower in smokers (5.2% versus 21.8%) and non-smokers (2.3% versus 34.4%). There were marginal significant interactions between treatment groups and smoking status for the proportion of HOPR ( P =0.058). There were significant interactions between treatment groups and carrier status of CYP2C19 LOF alleles for the proportion of HOPR among smokers ( P =0.04), but no significant interactions were found among non-smokers ( P =0.91). At 90±7 days, there were significant interactions between treatment groups and smoking status for the risk of new stroke (smokers, 7.0% versus 4.9%, hazard ratio [HR], 1.57 [95%CI, 0.65-3.79], P =0.39; non-smokers, 5.3% versus 13.5%, HR, 0.39 [95%CI, 0.17-0.91], P =0.01. P for interaction=0.02). Conclusions: Among patients with minor stroke or TIA, ticagrelor might be superior to clopidogrel in inhibiting platelet reactivity and reducing the risk of stroke, particularly in non-smokers. Carrier status of CYP2C19 LOF alleles might play a role in the impact of smoking status. Clinical Trial Registration : Clinicaltrials.gov NCT02506140.

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Effect of adjunctive dipyridamole to DAPT on platelet function profiles in stented patients with high platelet reactivity

Thrombosis and Haemostasis ◽

10.1160/th14-01-0040 ◽

2014 ◽

Vol 112 (12) ◽

pp. 1198-1208 ◽

Cited By ~ 6

Author(s):

Yongwhi Park ◽

Udaya Tantry ◽

Jong-Hwa Ahn ◽

Kye Hwan Kim ◽

Jin-Sin Koh ◽

...

Keyword(s):

Platelet Function ◽

Platelet Reactivity ◽

Pde5 Inhibitor ◽

Light Transmittance ◽

Reactivity Index ◽

Double Dose ◽

High Platelet Reactivity ◽

Number Of Patients ◽

The Impact

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.

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High platelet reactivity – the challenge of prolonged anticoagulation therapy after ACSI

Thrombosis and Haemostasis ◽

10.1160/th12-08-0582 ◽

2013 ◽

Vol 109 (05) ◽

pp. 799-807 ◽

Cited By ~ 4

Author(s):

Marc A. Brouwer ◽

Freek W. A. Verheugt ◽

Jeroen Focks

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Adjunctive Therapy ◽

Platelet Reactivity ◽

Vitamin K Antagonists ◽

Antiplatelet Agent ◽

Anticoagulation Therapy ◽

High Platelet Reactivity ◽

Coronary Syndrome ◽

The Impact

SummaryDespite dual antiplatelet therapy (DAPT), one-year event rates after acute coronary syndrome (ACS) vary from 9–12%. The development of novel oral anticoagulants (NOAC) without a need for monitoring has initiated renewed interest for prolonged adjunctive anticoagulation. Importantly, the cornerstone of treatment after ACS consists of long-term DAPT. In that context, the NOACs have only been tested as adjunctive therapy. Of all new agents, only rivaroxaban –in a substantially lower dose than used for atrial fibrillation– has been demonstrated to improve outcome, albeit at the cost of bleeding. In selected cases, adjunctive therapy with dose-adjusted vitamin-K antagonists (international normalized ratio [INR] 2.0–3.0) can be considered as well. These two strategies of prolonged anticoagulation can be considered in case of ‘high platelet reactivity’, i.e. in patients at high risk of recurrent thrombotic events despite DAPT. Both during admission and after discharge for ACS, the use of NOACs in doses indicated for atrial fibrillation is strictly contra-indicated in patients on DAPT. In case of post-discharge anticoagulation therapy for atrial fibrillation, patients should preferably receive vitamin-K antagonists (INR 2.0–3.0), with discontinuation of one antiplatelet agent as soon as clinically justifiable. Importantly, the impact of prolonged anticoagulation (low-dose rivaroxaban, vitamin-K antagonists) as adjunctive to DAPT after ACS has not been addressed with the most potent antiplatelet agents (prasugrel, ticagrelor) and merits further study. Despite the potential indication of prolonged oral anticoagulation as adjunctive treatment, it remains to be established whether anticoagulation therapy could also be an alternative for either aspirin or thienopyridine treatment in selected ACS patients on DAPT.

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Impact of Reticulated Platelets on the Antiplatelet Effect of the Intravenous P2Y12-Receptor Inhibitor Cangrelor

Thrombosis and Haemostasis ◽

10.1160/th17-07-0466 ◽

2018 ◽

Vol 118 (02) ◽

pp. 362-368 ◽

Cited By ~ 1

Author(s):

Christian Stratz ◽

Thomas Nührenberg ◽

Christian Valina ◽

Nikolaus Löffelhardt ◽

Kambis Mashayekhi ◽

...

Keyword(s):

Platelet Reactivity ◽

Coronary Intervention ◽

Platelet Inhibition ◽

P2y12 Receptor ◽

Elective Percutaneous Coronary Intervention ◽

Reticulated Platelets ◽

Impedance Aggregometry ◽

Percutaneous Coronary ◽

The Impact ◽

Receptor Inhibitor

Background Reticulated platelets are associated with impaired antiplatelet response to irreversibly acting P2Y12-receptor inhibitors. However, the impact of reticluated platelets (RP) on the reversibly acting injectable P2Y12-receptor inhibitor cangrelor is unknown. Thus, this study sought to investigate the influence of RP on cangrelor and transitioning strategies to oral P2Y12-receptor inhibitors. Methods This study randomized 110 patients undergoing elective percutaneous coronary intervention with use of cangrelor to different oral transitioning strategies loading with prasugrel 60 mg or ticagrelor 180 mg at the start of cangrelor (n = 45 each) or loading with clopidogrel 600 mg after discontinuation of cangrelor (n = 20). ADP-induced platelet reactivity was assessed by impedance aggregometry. Reticulated platelets were analysed by an automated whole blood flow cytometry and described as immature platelet count. Results There was no correlation of reticulated platelets and ADP-induced platelet reactivity in patients under treatment with cangrelor (r = 0.06, p = 0.47). This finding was consistent in all three transitioning strategies. On day 1 following treatment with cangrelor, the correlation of reticulated platelets and platelet reactivity was detectable again in patients receiving thienopyridines but not ticagrelor (all patients r = 0.37, p < 0.001; clopidogrel: r = 0.59, p = 0.01; prasugrel: r = 0.47, p < 0.001; ticagrelor r = 0.22, p = 0.13). Conclusion Platelet inhibition is not influenced by levels of reticulated platelets during infusion of cangrelor independent of oral P2Y12-receptor inhibitor transitioning strategy. These findings underline the potency of cangrelor as immediate and reversibly acting P2Y12-receptor inhibitor.

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Abstract T P341: Impact Of Cytochrome P450 2C19 Polymorphism On High On-treatment Platelet Reactivity In Stroke Patients Treated With Clopidogrel

Stroke ◽

10.1161/str.45.suppl_1.tp341 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Tomotaka Tanaka ◽

Shigeki Miyata ◽

Haruko Yamamoto ◽

Toshiyuki Miyata ◽

Kazuyuki Nagatsuka ◽

...

Keyword(s):

Platelet Aggregation ◽

Light Transmission ◽

Platelet Reactivity ◽

Platelet Rich Plasma ◽

Metabolic Activation ◽

Japanese Patients ◽

Paraoxonase 1 ◽

Loss Of Function ◽

Stroke Patients ◽

The Impact

BACKGROUND: Clopidogrel is one of the most commonly used anti-platelet drugs. Recent reports suggested the association of allelic variants of the genes modulating metabolic activation (CYP2C19 and paraoxonase-1) and bioavailability (ABCB1) of clopidogrel with high on-treatment platelet reactivity (HTPR), possibly resulting in the recurrence of thrombotic events. However, these studies mostly examined patients with coronary heart disease and the impact of these polymorphisms in stroke patients is largely unknown. METHODS: We conducted a multicenter, prospective cohort study of 518 Japanese patients from 14 hospitals who were administrated clopidogrel. Residual platelet reactivity was determined by a change in light transmission induced by platelet aggregation in platelet-rich plasma after adding ADP. The vasodilator-stimulated phosphoprotein (VASP) index was also measured using flow cytometry. We investigated the association of polymorphisms of aforementioned enzymes with HTPR. RESULTS: In terms of CYP2C19 loss-of-function polymorphisms (*2 and *3), the prevalence of intermediate (IM: *1*2 or *1*3) or poor (PM: *2*2, *2*3, or *3*3) metabolizer was much higher (IM: 47% or PM: 15%) in Japanese than in Caucasian populations. Residual platelet reactivity was significantly higher in PM and IM groups than that in the wild-type extensive metabolizer (EM: *1*1) group assessed by 5 μM ADP-induced platelet aggregation (PM: 69.4% ± 17.1%, IM: 59.7% ± 16.2%, EM: 51.5% ± 17.5%, p < 0.0001) and VASP index (PM: 66.6% ± 14.1%, IM: 52.4% ± 16.0%, EM: 42.9% ± 15.0%, p < 0.0001). Furthermore, HTPR determined by both assays was associated with the ABCB1 polymorphism (rs1045642) but not with the paraoxonase-1 Q192R mutation. CONCLUSIONS: Our results indicate that both CYP2C19 and ABCB1 polymorphisms significantly contribute to HTPR in stroke patients treated with clopidogrel. At present, we are monitoring these patients for a two-year period to determine whether these genetic variants and HTPR affect the recurrence of thrombotic events.

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Pharmacogenomic polygenic response score predicts ischaemic events and cardiovascular mortality in clopidogrel-treated patients

European Heart Journal - Cardiovascular Pharmacotherapy ◽

10.1093/ehjcvp/pvz045 ◽

2019 ◽

Vol 6 (4) ◽

pp. 203-210 ◽

Cited By ~ 15

Author(s):

Joshua P Lewis ◽

Joshua D Backman ◽

Jean-Luc Reny ◽

Thomas O Bergmeijer ◽

Braxton D Mitchell ◽

...

Keyword(s):

Platelet Reactivity ◽

Adenosine Diphosphate ◽

Platelet Inhibition ◽

Cardiovascular Death ◽

Individual Variability ◽

Clinical Event ◽

Major Adverse Cardiovascular Events ◽

Risk Alleles ◽

The Impact ◽

Response Score

Abstract Aims Clopidogrel is prescribed for the prevention of atherothrombotic events. While investigations have identified genetic determinants of inter-individual variability in on-treatment platelet inhibition (e.g. CYP2C19*2), evidence that these variants have clinical utility to predict major adverse cardiovascular events (CVEs) remains controversial. Methods and results We assessed the impact of 31 candidate gene polymorphisms on adenosine diphosphate (ADP)-stimulated platelet reactivity in 3391 clopidogrel-treated coronary artery disease patients of the International Clopidogrel Pharmacogenomics Consortium (ICPC). The influence of these polymorphisms on CVEs was tested in 2134 ICPC patients (N = 129 events) in whom clinical event data were available. Several variants were associated with on-treatment ADP-stimulated platelet reactivity (CYP2C19*2, P = 8.8 × 10−54; CES1 G143E, P = 1.3 × 10−16; CYP2C19*17, P = 9.5 × 10−10; CYP2B6 1294 + 53 C > T, P = 3.0 × 10−4; CYP2B6 516 G > T, P = 1.0 × 10−3; CYP2C9*2, P = 1.2 × 10−3; and CYP2C9*3, P = 1.5 × 10−3). While no individual variant was associated with CVEs, generation of a pharmacogenomic polygenic response score (PgxRS) revealed that patients who carried a greater number of alleles that associated with increased on-treatment platelet reactivity were more likely to experience CVEs (β = 0.17, SE 0.06, P = 0.01) and cardiovascular-related death (β = 0.43, SE 0.16, P = 0.007). Patients who carried eight or more risk alleles were significantly more likely to experience CVEs [odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.14–2.76, P = 0.01] and cardiovascular death (OR = 4.39, 95% CI 1.35–14.27, P = 0.01) compared to patients who carried six or fewer of these alleles. Conclusion Several polymorphisms impact clopidogrel response and PgxRS is a predictor of cardiovascular outcomes. Additional investigations that identify novel determinants of clopidogrel response and validating polygenic models may facilitate future precision medicine strategies.

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P4634Acute-phase high platelet reactivity with prasugrel loading is correlated with clinical outcomes during hospitalization in acute coronary syndrome

European Heart Journal ◽

10.1093/eurheartj/ehz745.1016 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

K Kuroda ◽

S Gentaro ◽

K Kawamura ◽

T Ono ◽

K Tokioka ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Clinical Outcomes ◽

Cox Regression ◽

Platelet Reactivity ◽

Curve Analysis ◽

Cox Regression Analysis ◽

High Platelet Reactivity ◽

Coronary Syndrome ◽

Post Procedure ◽

The Impact

Abstract Background/Introduction Although high platelet reactivity (HPR) seems to be associated with adverse cardiovascular events after percutaneous coronary intervention (PCI), the relationship between post-procedure HPR with prasugrel loading and clinical outcomes in acute coronary syndrome (ACS) is still unclear. Moreover, factors contributing to HPR in ACS with prasugrel loading are also unknown. Purpose This study aimed to assess the impact of post-procedure HPR with prasugrel loading on clinical outcomes in ACS during hospitalization, as well as to define appropriate cut-off values and identify factors contributing to HPR. Methods We performed a single-centre, retrospective observational study that enrolled 132 patients who underwent emergent PCI for ACS with prasugrel loading. The P2Y12 reaction unit (PRU) value was measured immediately after PCI with the VerifyNowR System. The primary endpoint was major adverse cardiac events (MACE, defined as the composite of death, myocardial infarction, stroke, heart failure, ventricular arrhythmia needing defibrillation). Results Mean patient age (standard deviation) was 70.7 (±12.5) years, 76% were male, and average time from prasugrel intake to PRU calculation was 101 (±48.8) min. During a mean hospital stay of 15.4 (±8.0) days, there were 22 (16%) MACE events and 6 (4%) deaths. The post-procedure PRU value was 241±66. HPR was significantly higher in MACE group than non-MACE group [287 (±55) vs 232 (±64), p<0.001]. The ROC curve analysis of PRU for discriminating significant in-hospital MACE showed a cut off value of 293 (sensitivity: 64%, specificity: 84% [AUC=0.764, p<0.0001]). Thus, 33 patients (25%) were found to have HPR (PRU>293) immediately after emergent PCI. Kaplan-Meier curve analysis showed MACE events occurred more frequently in the HPR group than in the non-HPR group (42% vs 8%, log rank p<0.001). Multiple Cox regression analysis showed that peak creatine phosphokinase >3,000 U/L and HPR were independent predictors of MACE in patients with ACS who underwent PCI (OR 4.96, 95% CI 1.86–13.26, p=0.001, and OR 7.52, 95% CI 2.73–20.7, p<0.0001, respectively). HPR was significantly correlated with age, female sex, and reference lumen short diameter (pre-dilation) used in PCI. Conclusion HPR was significantly associated with adverse event during hospitalization in ACS patients. Female patients with large culprit lesion diameter were more likely to have HPR. Appropriate cut-off value of HPR in this study was 293. HPR in early-phase of ACS with prasugrel loading is a useful predictor of adverse events during hospitalization.

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