P2Y12 Reaction Units Values Research Articles

Differential prognostic significance of platelet reactivity based on ischemic risk after percutaneous coronary intervention

Abstract Background High platelet reactivity (HPR) in patients underwent percutaneous coronary intervention (PCI) is a potential risk factor of adverse cardiovascular events. It is not well understood in which patients HPR is particularly clinically important. Purpose We aimed to elucidate the prognostic value of high platelet reactivity (HPR), across varying levels of ischemic risk categorized by the CHADS-P2A2RC score in a large registry. Methods We retrospectively analyzed 11,714 patients who underwent PCI in the PTRG-DES registry. Ischemic risk was stratified using the CHADS-P2A2RC score into low (score ≤ 1), moderate (score 2–3), and high (score ≥ 4) groups. HPR was defined as a P2Y12 Reaction Unit (PRU) value ≥252. The incidence of major adverse cardiac and cerebrovascular events (MACCE) during 5- year follow-up was the primary outcome. Results During the median follow-up of 37.6 months (IQR, 12.0–60.8), a total of 709 MACCEs (6.1%) (392 deaths [3.3%], 172 non-fatal MI [1.5%], 62 ST [0.5%] and 181 non-fatal stroke [1.5%]), and 324 cases of major bleeding (2.8%) occurred. The high-risk group has the highest incidence of MACCE during 5-year follow-up unadjusted HR of 4.206, 95% CI 3.204–5.521. Among the 2,577 low-risk patients, HPR did not significantly affect MACCE incidence (HR 1.366, 95% CI 0.798–2.336, p=0.253). In the moderate-risk cohort of 5,417 patients, HPR conferred a modest increase in MACCE risk (HR 1.289, 95% CI 1.008–1.649, p=0.043). Notably, the high-risk group demonstrated a significant association between HPR and MACCE (HR 1.385, 95% CI 1.135–1.692, p<0.001). Conclusion HPR is a potent risk factor of long-term outcomes following PCI, especially in patients with a high ischemic risk based on CHADS-P2A2RC scoring. The results highlight the varying impact of platelet reactivity depending on the level of ischemic risk, indicating the importance of tailored antiplatelet therapy in high-risk group to improve clinical outcomes.

High platelet reactivity strongly predicts early stent thrombosis in patients with drug-eluting stent implantation

Stent thrombosis (ST) is a fatal complication after percutaneous coronary intervention (PCI). The association between P2Y12 reaction unit (PRU) level and stent thrombosis occurrence remains unclear. Based on the multicenter, observational PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) registry of patients with drug-eluting stents (DES) implantation, a total of 11,714 patients with PRU values were analyzed. We sought to identify the predictors of early stent thrombosis (EST) and compared the primary outcome, a composite of cardiac death, myocardial infarction, and revascularization, between EST and non-EST groups. EST, defined as definite ST within 1 month after index PCI, occurred in 51 patients. PRU values were significantly higher in the EST group (263.5 ± 70.8 vs. 217.5 ± 78.7, p < 0.001). In multivariable analysis, PRU ≥ 252 (OR, 5.10; 95% CI 1.58–16.46; p = 0.006) and aspirin reaction unit ≥ 414 (OR 4.85; 95% CI 1.07–21.97; p = 0.040) were independent predictors of EST. The cumulative incidence of primary composite outcome at one year was significantly higher in the EST group (38.2% vs. 3.9%, Log-rank p < 0.001). In patients treated with clopidogrel after successful DES implantation, EST was associated with higher platelet reactivities, and a greater risk of cardiovascular events.Trial Registration: clinicaltrials.gov Identifier: NCT04734028.

Platelet Function Testing to Guide Cangrelor Dosing in Patients with Temporary Mechanical Circulatory Support or as a Bridge to Procedure.

Cangrelor is a rapid-acting, intravenous P2Y12 inhibitor that can be used in patients after percutaneous coronary intervention who require mechanical circulatory support or as a bridge to procedure. We retrospectively reviewed adult patients who received platelet function testing (PFT) with the VerifyNow P2Y12 assay while on cangrelor from March 2021 through November 2022. All patients were initiated on 0.75 mcg/kg/min of cangrelor with P2Y12 reaction unit (PRU) values collected 12-24 h after initiation. Cangrelor doses were adjusted per protocol to maintain PRU values of 85-208. A total of 42 patients were included. Thirty-eight patients (90.5%) required temporary mechanical circulatory support while on cangrelor, and 4 patients (9.5%) received cangrelor as a bridge to procedure. The median cangrelor maintenance dose was 0.5 (interquartile range [IQR]: 0.375-0.75) mcg/kg/min, and the median time in therapeutic range with a PRU value between 85 and 208 was 66.6% (IQR: 39.6%-100%). No patients experienced stent thrombosis. A composite major adverse cardiovascular event occurred in 4 patients (9.5%), and major bleeding occurred in 16 patients (38.1%). Compared to empiric cangrelor dosing of 0.75 mcg/kg/min, PFT-guided cangrelor dose adjustment was associated with a median drug cost savings of $1605.60 (IQR: $0-4281.56). Utilizing PFT with cangrelor may allow for lower, individualized dosing while preventing stent thrombosis.

Periprocedural antiplatelet medication assessed by VerifyNow for neuroendovascular treatment: Comparison of prasugrel with clopidogrel

Objective The maintenance dose of prasugrel (PRAS) for neuroendovascular treatment requires much research. We report the antiplatelet effect of PRAS measured by VerifyNow P2Y12 reaction units (PRUs) in patients during the perioperative period of neuroendovascular treatment. Methods Between January 2017 and January 2023, 230 patients who underwent endovascular treatment for unruptured intracranial aneurysms or carotid artery stenosis at our institution were retrospectively identified. Patients received dual antiplatelet therapy with 100 mg aspirin (ASA) and 75 mg clopidogrel (CLP)/day (CLP group, n = 186) or 100 mg ASA and 3.75 mg PRAS/day (PRAS group, n = 44) 2 weeks before the procedures. The PRU value was compared between the CLP and PRAS groups. In the study, we defined 95≦PRU &lt; 208 as the optimal range. Perioperative complications within seven days of surgery were also analyzed. Results The mean value of PRU was significantly low in the PRAS group (179.13 ± 66.03 in CLP vs. 154.75 ± 54.01 in PRAS, p = 0.024). The proportion of the patients who exhibited 95≦PRU &lt; 208 was significantly higher in the PRAS group (55.4% vs. 72.7%, p = 0.036). Ischemic and hemorrhagic complication rates were not significantly different between the CLP and PRAS groups (7.6% vs. 0%, p = 0.076; 4.7% vs. 0%, p = 0.361). The ischemic complication rate was higher in patients with a PRU &gt; 208 than in those with PRU &lt; 208 (12.5% vs. 3.8%, p = 0.044). The hemorrhagic complication rate was not significantly different between the PRU &lt; 95 and 95≦PRU groups (8.4% vs. 3.2%, p = 0.224). Conclusions Maintenance dose PRAS further decreased the PRU value and reached the optimal range in more cases than CLP during the perioperative period of neuroendovascular treatment. Ischemic complications significantly increased in the 208 &lt; PRU group.

Association between high platelet reactivity and early stent thrombosis in patients with drug-eluting stent implantation

Abstract Background Stent thrombosis (ST) is a potentially fatal complication after percutaneous coronary intervention (PCI). The association between P2Y12 reaction unit (PRU) level and stent thrombosis occurrence is not fully elucidated. Methods Based on the multicenter, observational PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) registry of patients with drug-eluting stents (DES) implantation, a total of 11,714 patients with PRU values were identified. The independent predictors of early stent thrombosis (EST) were assessed. The primary outcome after EST was the composite of cardiac death, myocardial infarction and any revascularisation. Key secondary outcomes were all-cause death, cardiac death, myocardial infarction, and any revascularisation. Results EST, defined as definite ST in less than 1 month after index PCI, was identified in a total of 51 patients. The PRU value was significantly higher in the EST group (263.5 ± 70.8 vs. 217.5 ± 78.7, p&amp;lt;0.001). In multivariable analysis, having a PRU value of ≥252 (OR, 5.10; 95% CI, 1.58-16.46; p=0.006) and an ARU value of ≥414 (OR 4.85; 95% CI, 1.07-21.97; p=0.040) were significant predictors of EST. The use of first-generation DES (OR 3.56; 95% CI, 0.98-12.99; p=0.054) also posed a higher risk for EST occurrence with a borderline significance. Cumulative incidence of the primary composite outcome was significantly higher in patients with EST (HR 18.7; 95% CI 12.8-27.3; p&amp;lt;0.001). Conclusion In patients treated with clopidogrel after successful DES implantation, EST was associated with higher PRU values, and a greater rate of adverse outcomes, including all-cause death and MI.

Clopidogrel-Related High Residual Platelet Reactivity Associated with Estimated Glomerular Filtration Rate in Patients with Acute Ischemic Stroke

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 July 1, 2017, to June 30, 2018, at Shanghai TCM-Integrated Hospital. Renal function was measured within 24 h of enrollment 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 with 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 chronic kidney disease [CKD]: OR = 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.

Time-dependent changes in P2Y12 reaction unit values for predicting the different types of cardiovascular events in patients with ischemic heart disease.

Several studies have investigated the association between P2Y12 reaction unit (PRU) value and major adverse cardiovascular events (MACEs) in patients with ischemic heart disease, but there is no well-established consensus on the utility of PRU value. Furthermore, the optimal PRU cut-off value varied with studies. One reason may be that the endpoints and observation periods differed, depending on the study. This study aimed to investigate the optimal cut-off and predictive ability of the PRU value for predicting cardiovascular events, while considering different endpoints and observation periods. We surveyed a total of 338 patients receiving P2Y12 inhibitors and measured PRU during cardiac catheterization. Using time-dependent receiver operating characteristic analysis, we evaluated the cut-off and area under curve (AUC) of the PRU value for two MACEs (MACE ①: composite of death, myocardial infarction, stent thrombosis, and cerebral infarction; MACE ②: composite of MACE ① and target vessel revascularization) at 6, 12, 24 and 36months after cardiac catheterization. MACE ① occurred in 18 cases and MACE ② in 32 cases. The PRU cut-off values at 6, 12, 24, and 36months were 257, 238, 217, and 216, respectively, for MACE ① and 250, 238, 209, and 204, respectively, for MACE ②. The AUCs at 6, 12, 24, and 36months were 0.753, 0.832, 0.718, and 0.717, respectively, for MACE ① and 0.724, 0.722, 0.664, and 0.682, respectively, for MACE ②. The optimal cut-off and predictive ability of PRU values for cardiovascular events varied depending on different endpoints and duration of the observation periods. A relatively high PRU value is effective for short-term event suppression, but a low value is required for long-term event suppression.

Impact of Low-Dose Prasugrel on Platelet Reactivity in Chronic Phase of Post-Percutaneous Coronary Intervention (CHAPERON): a Prospective Cohort Study.

Asians often face the problems of clopidogrel resistance and East Asian paradox. This study aimed to evaluate the effects of P2Y12 inhibitors, including low-dose prasugrel 2.5mg, on the P2Y12 reaction unit (PRU) in the chronic phase after percutaneous coronary intervention (PCI). A total of 348 patients were studied. PRU was measured 6-12months after PCI and subsequently, 6months later using a P2Y12 assay, respectively. This study evaluated the proportion of bleeding risk (PRU ≤ 85) and ischemic risk (PRU ≥ 239) as primary endpoints, and the prediction of bleeding risk and ischemic risk using multivariable logistic regression analysis. At baseline, 136 patients (39%) received prasugrel 3.75mg, 48 patients (14%) received prasugrel 2.5mg, and 164 patients (47%) received clopidogrel 75mg. Clopidogrel 75mg had a significantly higher proportion of ischemic risk within one year after PCI than the other groups, and was an independent predictor for ischemic risk with reference of prasugrel 3.75mg. In addition, switching from clopidogrel 75mg to prasugrel 2.5mg significantly lowered and aggregated the PRU value. Whereas, dose reduction of prasugrel had a significantly lower proportion of bleeding risk over one year after PCI than the continuation of prasugrel 3.75mg, and was an independent predictor for bleeding risk with reference of continuation of prasugrel 3.75mg. Prasugrel 2.5mg has a lower ischemic risk and a more stable PRU value compared with clopidogrel treatment. Prasugrel also contributes to a decline in bleeding risk with concomitant dose reduction. University Hospital Medical Information Network (UMIN), ID: UMIN000029541, Date: October 16, 2017 ( https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033395 ).

Association of Antiretroviral Therapy with Platelet Function and Systemic Inflammatory Response in People Living with HIV: A Cross-Sectional Study.

People living with HIV (PLWHIV) present an increased risk of adverse cardiovascular events. We aimed to assess whether antiretroviral therapy (ART) pharmacologically enhances platelet reactivity and platelet activation intensity, and explore the potential association with underlying inflammatory status. This was a cross-sectional cohort study carried out among PLWHIV on diverse ART regimens. Platelet reactivity and activation intensity were assessed using the bedside point-of-care VerifyNow assay, in P2Y12 reaction units (PRU), measurements of monocyte-platelet complexes, and P-selectin and GPIIb/IIIa expression increase, following activation with ADP, respectively. Levels of major inflammatory markers and whole blood parameters were also evaluated. In total, 71 PLWHIV, 59 on ART and 22 healthy controls, were included in this study. PRU values were significantly elevated in PLWHIV compared to controls [Mean; 257.85 vs. 196.67, p < 0.0001], but no significant differences were noted between ART-naïve or ART-experienced PLWHIV, or between TAF/TDF and ABC based regimens, similar to systemic inflammatory response. However, within-group analysis showed that PRUs were significantly higher in ABC/PI vs ABC/INSTI or TAF/TDF + PI patients, in line with levels of IL-2. PRU values did not correlate strongly with CD4 counts, viral load, or cytokine values. P-selectin and GPIIb/IIIa expression increased following ADP activation and were significantly more prominent in PLWHIV (p < 0.005). Platelet reactivity and platelet activation intensity were shown to be increased in PLWHIV, but they did not appear to be related to ART initiation, similar to the underlying systemic inflammatory response.

747 HIGH PLATELET REACTIVITY AFTER DAPT IN PATIENTS WITH ACUTE CORONARY SYNDROME AND ATRIAL FIBRILLATION

Abstract Background The incidence of atrial fibrillation (AF) in patients who undergo percutaneous coronary intervention (PCI) is not negligible, especially in the elderly. Both oral anticoagulation (OAC) and dual anti-platelet therapy (DAPT) are recommended by main guidelines, therefore is essential to balance the prevention of ischemic events with the risk of bleeding. Evidences from literature suggest that incidence of anti-platelet therapy resistance is higher in elderly patients. There is a paucity of data about the response to antiplatelet therapy in patients with AF. The purpose of this study is to analyze platelet reactivity during DAPT (aspirin + clopidogrel) in elderly patients hospitalized for acute coronary syndrome (ACS), stratifying them by the presence or absence of AF. Methods We analyzed data of patients admitted to our center for ACS. All patients were ≥ 75 years old and treated with DAPT (Aspirin 100 mg daily and Clopidogrel 75 mg daily). At discharge they were tested with a point-of-care antiplatelet-function test (VerifyNow assay) to assess the platelet response to aspirin in aspirin-reaction units (ARU) and to clopidogrel in P2Y12-reaction units (PRU). Low response to aspirin was defined as ARU ≥550; low response to clopidogrel was defined as PRU ≥208; high response was defined as PRU values ≤ 85. Results Among the 216 patients included in the registry we selected 154 of these [median age 81 (IQR 77-87) years; 45% female] who were submitted to the platelet function tested before discharge. Patients were divided into two groups: AF (43 pts); non-AF (111 pts). The table shows the platelet reactivity values by two groups. Conclusions In this series of elderly patients with ACS, AF was associated with higher residual platelet reactivity with both clopidogrel and aspirin. AF patients were significantly less responsive to clopidogrel than non-AF, while among non-AF patients there were significantly more high responders. No difference was found for aspirin low responders between AF and non-AF group. This evidence could assume clinical significance in the choice of antiplatelet drugs to be combined with chronic anticoagulant therapy for AF.

Thromboembolic Events Detected by Diffusion-Weighted Magnetic Resonance Imaging after Flow Diverter Treatment: The Impact of Procedure Time

Periprocedural thromboembolism is a serious complication of endovascular treatment for intracranial aneurysms. In addition to symptomatic ischemia, asymptomatic postprocedural diffusion-weighted image-positive lesions (DPLs) are considered important. However, few studies have reported significant risk factors associated with DPLs and symptomatic ischemic stroke after flow diverter (FD) treatment. This study aimed to investigate the frequency and risk factors associated with DPLs after FD treatment. Between November 2015 and December 2021, 84 patients harboring 85 untreated, unruptured intracranial aneurysms treated with FD were enrolled. DPLs after FD treatment were confirmed in 74 patients (87.1%), among whom 69 (93.2%) were clinically asymptomatic. In the univariate analyses, age >55years (P= 0.040), smoking (P= 0.023), preprocedural P2Y12 reaction unit value of >185 (P= 0.030), larger dome size of >9.3mm (P= 0.013), and prolonged procedure time >80minutes (P < 0.001) were significantly associated with postprocedural DPLs. In the multiple logistic regression model, only prolonged procedure time >80minutes (oddsratio, 10.72; 95% confidence interval, 1.346-233.899; P= 0.023) was statistically significant. The mediator effect showed that the association between procedure time and the occurrence of DPLs was not significantly modified by any other factors, although only adjunctive coiling showed a tendency (P-value for interaction= 0.070). Prolonged procedure time >80minutes was the only identifiable factor related to postprocedural DPLs. Adjunctive coiling tended to mediate the effects of a prolonged procedure time on the occurrence of DPLs after FD treatment.

Effect of CYP2C19 status on platelet reactivity in Taiwanese acute coronary syndrome patients switching to prasugrel from clopidogrel: Switch Study

Pharmacogenetics is a potential driver of the "East Asian paradox," in which East Asian acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy (DAPT) with clopidogrel following percutaneous coronary intervention (PCI) demonstrate higher levels of platelet reactivity on treatment than Western patients, yet have lower ischemic risk and higher bleeding risk at comparable doses. However, the impact of pharmacogenetics, particularly regarding CYP2C19 genotype, on the pharmacodynamics of P2Y12 inhibitors has not been extensively studied in Taiwanese ACS patients as yet. CYP2C19 genotyping and pharmacogenetic analysis was conducted on 102 subjects from the Switch Study, a multicenter, single-arm, open-label intervention study that examined the effects on platelet activity and clinical outcomes of switching from clopidogrel (75mg daily) to low-dose prasugrel (3.75mg daily) for maintenance DAPT after PCI in 203 Taiwanese ACS patients. Genotyping results revealed that 43.1% were CYP2C19 extensive metabolizers (EM), while 56.9% were reduced metabolizers (RM). After switching to prasugrel, mean P2Y12 reaction units (PRU) values were significantly reduced in both EM and RM populations, while the proportion of high on-treatment platelet reactivity (HPR) patients significantly declined in RM patients. No increase in bleeding risk after switching was observed during follow-up. Multivariate analysis indicated that for RM patients, low estimated glomerular filtration rate (eGFR) and low hemoglobin were associated with greater HPR risk on clopidogrel, but not after switching to prasugrel. Switching to low-dose prasugrel from clopidogrel reduced mean PRU levels and proportion of HPR patients, with more significant reduction in RM patients.

Relationship between platelet aggregation and stroke risk after percutaneous coronary intervention: a PENDULUM analysis

In patients undergoing percutaneous coronary intervention (PCI) with a stent, high on-treatment platelet reactivity may be associated with an increased risk of stroke. This post hoc analysis of the PENDULUM registry compared the risk of post-PCI stroke according to on-treatment P2Y12 reaction unit (PRU) values. Patients aged ≥ 20 years who underwent PCI were stratified by baseline PRU (at 12 and 48 h post-PCI) as either high (HPR, > 208), optimal (OPR, > 85 to ≤ 208), or low on-treatment platelet reactivity (LPR, ≤ 85). The incidences of non-fatal ischemic and non-ischemic stroke through to 12 months post-PCI were recorded. Almost all enrolled patients (6102/6267 [97.4%]) had a risk factor for ischemic stroke, and most were receiving dual antiplatelet therapy. Of the 5906 patients with PRU data (HPR, n = 2227; OPR, n = 3002; LPR, n = 677), 47 had a non-fatal stroke post-PCI (cumulative incidence: 0.68%, ischemic; 0.18%, non-ischemic stroke). Patients with a non-fatal ischemic stroke event had statistically significantly higher post-PCI PRU values versus those without an event (P = 0.037). The incidence of non-fatal non-ischemic stroke was not related to PRU value. When the patients were stratified by PRU ≤ 153 versus > 153 at 12–48 h post-PCI, a significant difference was observed in the cumulative incidence of non-fatal stroke at 12 months (P = 0.044). We found that patients with ischemic stroke tended to have higher PRU values at 12–48 h after PCI versus those without ischemic stroke.Clinical trial registration: UMIN000020332.

Impact of high platelet reactivity on left ventricular remodeling in patients with acute coronary syndrome

Abstract Background/Introduction Previous studies demonstrated that high platelet reactivity (HPR) predicts future cardiovascular death and coronary events in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). However, few studies have focused on the impact of HPR on left ventricular remodeling (LVR) and each echocardiographic parameter. Purpose The purpose of this study was to investigate the impact of HPR in ACS patients on LVR and changes in echocardiographic volume indexes and LV ejection fraction. Methods This is a retrospective cohort study of prospectively collected data in a single center that enrolled patients who underwent emergency PCI for ACS including STEMI and NSTEMI with prasugrel loading. The primary outcome of the study was LVR associated with HPR. Secondary endpoints were changes in indexed LVESV, LVEDV, LVEF, E/e' and LAVI between baseline and follow-up. The P2Y12 reaction unit (PRU) value in response to prasugrel was assessed by the VerifyNow P2Y12 assay. Blood samples were collected once per procedure immediately after PCI. LVR index was calculated as the relative change in LVEDV observed at follow-up compared with baseline. LVR was defined as a relative increase in LVEDV ≥20%, measured at follow-up visit compared with the baseline value before discharge. Results A total of 196 ACS patients who underwent emergency PCI between January 2016 and July 2020 were enrolled in the study. The mean age of the study population was 69.9 years, and 76.0% were male. On echocardiography at follow up visit of mean duration of 7.0±4.0 months, LVR was found in 38 patients (19.4%). The optimal cutoff for PRU associated with increased LVR assessed by receiver-operating characteristic curve analysis was 245.5 (AUC: 0.656; 95% CI: 0.564 to 0.749; p=0.003). On the basis of this cutoff, HPR was found in 82 patients (42.1%) and the prevalence of LVR was significantly higher in the HPR group compared to the non-HPR group (30.5% vs. 11.4%; p=0.001). Multiple Cox regression analysis showed that HPR was an independent predictor of LVR (OR 4.22, 95% CI 1.83–9.71, p=0.001). In addition, Δ% EDV and Δ% ESV increased in the HPR group, and decreased in the non-HPR group with significant differences (5.8±32.6% vs. −8.0±26.2% in Δ% EDV; p=0.002, 2.0±37.5% vs. −13.3±33.0% in Δ% ESV; p=0.004, respectively). Δ%EF, Δ%E/e', Δ%LAVI were numerically improved in the non-HPR group compared with the HPR group, but this difference did not reach statistical significance. Conclusion In patients with ACS, HPR defined as PRU ≥246 immediately after emergency PCI was an independent predictor of LVR in the chronic phase. Funding Acknowledgement Type of funding sources: None. Predictors of the presence of LVRChanges (Δ%) of LVEDV and LVESV

Antiplatelet Therapy and Periprocedural Risk Factor Analysis for Pipeline Embolization Device Treatment of Unruptured Internal Carotid Artery Aneurysms: A Retrospective, Multicenter Analysis

Aneurysm treatment using the Pipeline Embolization Device has been established but appropriate maintenance of dual antiplatelet therapy (APT) is essential. This multicenter retrospective study assessed whether APT was properly adjusted for clopidogrel resistance and identified risk factors associated with periprocedural complications. Consecutive cases of use of the Pipeline Embolization Device for internal carotid artery aneurysms (>10 mm) between November 2015 and April 2020 were analyzed. Dual APT (aspirin+ clopidogrel) was prescribed before treatment. If preprocedural P2Y12 reaction unit (PRU) values were >240, APT was adjusted. Periprocedural complications were compared between APT nonadjustment and adjustment groups and periprocedural risk factors were also analyzed. A total of 162 procedures were assessed. The mean maximum aneurysm size was 15.35 mm. APT adjustment was required in 47 cases (29.0%), primarily by switching to prasugrel. There were no significant differences in complication incidence between the 2 groups even after propensity score matching. The risk factor independently associated with ischemic complications was a neck size of 8 mm or larger (odds ratio [OR], 5.25; P= 0.018) and restricting analysis to the APT nonadjustment group showed PRU values of 190 or higher (OR, 5.84; P= 0.047) and neck sizes of 8 mm or larger (OR, 7.05; P= 0.029) as significant factors. The risk factor independently associated with hemorrhagic complications was a neck size of 7 mm or larger (OR, 11.57; P= 0.023). APT adjustment for clopidogrel resistance was safe and effective. Neck width was a risk factor for both ischemic and hemorrhagic complications. PRU values of 190 or higher were also associated with ischemic complications.

Pharmacodynamics and Outcomes of a De-Escalation Strategy with Half-Dose Prasugrel or Ticagrelor in East Asians Patients with Acute Coronary Syndrome: Results from HOPE-TAILOR Trial.

East Asians treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) generally experience more intense platelet inhibitory responses resulting in an increased risk of major bleeding. Whether a half-dose de-escalation strategy improves the net clinical benefit in Korean patients with acute coronary syndrome (ACS) remains uncertain. A total of 120 patients were pragmatically randomized to either prasugrel (n = 39, 60 mg loading dose (LD)/10 mg maintenance dose (MD)), ticagrelor (n = 40, 180 mg LD/90 mg MD), or clopidogrel (n = 41, 600 mg LD/75 mg MD) followed by a half-dose reduction at 1 month, or conventional dose 75 mg clopidogrel. The primary endpoint was the incidence of optimal platelet reactivity (OPR), defined as a P2Y12 reaction unit (PRU) value between 85 and 208 (by VerifyNow) at 3 months. Ticagrelor treatment achieved a significantly lower PRU compared with prasugrel and clopidogrel (31.0 ± 34.5 vs. 93.2 ± 57.1 vs. 153.1 ± 69.4), resulting in the lowest rate of OPR (12.5% vs. 48.7% vs. 63.4%). At 9 months, the minor bleeding was significantly higher with potent P2Y12 inhibitors than with clopidogrel (31.6% vs. 12.2%; HR, 2.93; 95% CI, 1.12–7.75). Only a few patients experienced ischemic complications. In Korean ACS patients, a de-escalation strategy with half-dose ticagrelor and prasugrel from standard dose increased the OPR rate significantly. Half-dose ticagrelor had a lower OPR rate and greater platelet inhibition compared with half-dose prasugrel as well as conventional-dose clopidogrel. Optimal dose reduction strategies for potent P2Y12 inhibitors require further investigation to balance safety and efficacy.

The utility of platelet inhibition testing in patients undergoing Pipeline embolization of intracranial aneurysms

BackgroundThe utility of using the VerifyNow P2Y12 platelet inhibition assay in patients undergoing Pipeline embolization of intracranial aneurysms remains controversial. As we have routinely employed the assay for patients undergoing...

Impact of Chronic Kidney Disease and Platelet Reactivity on Clinical Outcomes Following Percutaneous Coronary Intervention.

We investigated the interaction between chronic kidney disease (CKD) and high platelet reactivity (HPR) in determining long-term clinical outcomes following elective PCI for stable coronary artery disease (CAD). A total of 500 patients treated with aspirin and clopidogrel were divided based on the presence of CKD (defined as glomerular filtration rate of < 60 ml/min/1.73 m2) and HPR (defined as a P2Y12 reaction unit value ≥ 240 at VerifyNow assay). Primary endpoint was the occurrence of major adverse clinical events (MACE) at 5 years. Patients with both CKD and HPR showed the highest estimates of MACE (25.6%, p = 0.005), all-cause death (17.9%, p = 0.004), and cardiac death (7.7%, p = 0.004). The combination of CKD and HPR was an independent predictor of MACE (HR 3.12, 95% CI 1.46-6.68, p = 0.003). In conclusion, the combination of CKD and HPR identifies a cohort of patients with the highest risk of MACE at 5 years.

Prasugrel switching from clopidogrel after percutaneous coronary intervention for acute coronary syndrome in Taiwanese patients: an analysis of safety and efficacy

The recommended maintenance dose of prasugrel for East Asian populations (i.e., Japanese and Taiwanese) is 3.75 mg as part of dual antiplatelet therapy (DAPT) for the prevention of recurrent ischemia and stent thrombosis in acute coronary syndrome (ACS). This modified dosage regimen has been established in studies conducted in Japan; however, the efficacy and safety of switching from clopidogrel to prasugrel DAPT among Taiwanese patients remain to be explored. In this phase IV, multicenter, single-arm, open-label study, we evaluated the 4-week pharmacodynamic response, and the 48-week safety outcomes of prasugrel 3.75 mg after a switch from clopidogrel in Taiwanese ACS patients. A total of 203 prasugrel-naïve ACS patients (over 90% male) who had received post-PCI clopidogrel DAPT for at least 2 weeks were enrolled from ten medical centers in Taiwan and subsequently switched to prasugrel 3.75 mg DAPT. Four weeks after the switch, P2Y12 reaction unit (PRU) values were significantly decreased in the total cohort (mean − 18.2 ± 48.1; 95% confidence interval − 24.9 to − 11.5, p < 0.001), and there was an overall consistent antiplatelet response in the treated subjects. The proportion of patients with high on-treatment platelet reactivity (HPR; PRU > 208) dropped from 23.5 to 10% (p < 0.001). Female sex was associated with a greater PRU reduction with prasugrel, whereas HPR at baseline, age ≥ 65 years, and body mass index ≥ 25 best predicted HPR at Week 4. Throughout the 48-week treatment with prasugrel, the incidences of MACE (1.0%) and TIMI major bleeding (2.0%) were rather low, accompanying an acceptable safety profile of TIMI minor (6.4%) and non-major, non-minor clinically relevant bleeding (3.0%). Overall, switching to the maintenance dose of prasugrel (3.75 mg) was observed to be effective and well tolerated among post-PCI ACS patients in Taiwan. Clinical Trial Registration Number: NCT03672097.

Active management of the target P2Y12 reaction unit range in patients undergoing stent-assisted coil embolization for unruptured cerebral aneurysms

BackgroundPlatelet function tests have been increasingly adopted to measure patient responses to antiplatelet drugs, and to predict complications. However, no established optimal antiplatelet management for stent-assisted coil embolization (SAC) have...