Dataset Information

An optimal window of platelet reactivity by LTA assay for patients undergoing percutaneous coronary intervention.

ABSTRACT:

Objective

This study was aimed to determine how platelet reactivity (PR) on dual antiplatelet therapy predicts ischemic and bleeding events in patients underwent percutaneous coronary intervention (PCI).

Design

A total of 2768 patients who had received coronary stent implantation and had taken aspirin 100 mg in combination with clopidogrel 75 mg daily for > 5 days were consecutively screened and 1885 were enrolled. The recruited patients were followed-up for 12 months. The primary end-point was the net adverse clinical events (NACE) of cardiovascular death, nonfatal myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST) and any bleeding.

Result

1709 patients completed the clinical follow-up. By using the receiver operating characteristic (ROC) curve analysis, the optimal cut-off values were found to be 37.5 and 25.5% respectively in predicting ischemic and bleeding events. Patients were classified into 2 groups according to PR: inside the window group (IW) [adenosine diphosphate (ADP) induced platelet aggregation (PL_ADP) 25.5-37.4%)] and outside the window group (OW) (PL_ADP < 25.5% or ≥ 37.5%). The incidence of NACE was 16.8 and 23.1% respectively in the IW and OW group. The hazard ratio of NACE in IW group was significantly lower [0.69 (95% CI, 0.54-0.89, P = 0.004)] than that in the OW group during 12-month follow-up.

Conclusion

An optimal therapeutic window of 25.5-37.4% for PL_ADP predicts the lowest risk of NACE, which could be referred for tailored antiplatelet treatment while using LTA assay.

Trial registration

Trial registration number: ClinicalTrials.gov NCT01968499 . Registered 18 October 2013 - Retrospectively registered.

SUBMITTER: Wang J

PROVIDER: S-EPMC8527808 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

An optimal window of platelet reactivity by LTA assay for patients undergoing percutaneous coronary intervention.

Wang Jing J Wang Jing J Dong Zhou Z Ma Jiazheng J Teng Jianzhen J Wang Tong T Zhang Xiaofeng X Gu Qian Q Ye Zekang Z Ullah Inam I Tan Chuchu C Abdus Samee S Shi Lu L Gong Xiaoxuan X Li Chunjian C

Thrombosis journal 20211019 1

<h4>Objective</h4>This study was aimed to determine how platelet reactivity (PR) on dual antiplatelet therapy predicts ischemic and bleeding events in patients underwent percutaneous coronary intervention (PCI).<h4>Design</h4>A total of 2768 patients who had received coronary stent implantation and had taken aspirin 100 mg in combination with clopidogrel 75 mg daily for > 5 days were consecutively screened and 1885 were enrolled. The recruited patients were followed-up for 12 months. The primary ...[more]

PMID: 34666778

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Project description:BackgroundEast Asian patients receiving treatment with the potent P2Y12 inhibitors prasugrel or ticagrelor experience more potent platelet inhibition than with clopidogrel.MethodsThis study investigated differences in OPR rates with reduced doses of prasugrel (n = 38) or ticagrelor (n = 40) for maintenance therapy in 118 Korean ACS patients who had undergone PCI, in comparison to conventional-dose clopidogrel (n = 40). We assessed drug responses at one- and three-months post-PCI with VerifyNow and multiple electrode aggregometry assays.ResultsAt the one-month period, patients receiving standard-dose prasugrel or ticagrelor had lower platelet reactivity as determined by the three assays than those receiving the conventional dose of clopidogrel (VN: p = 0.000; MEA: p = 0.000; LTA: p = 0.000). At the 3-month point, platelet reactivity was lower in those receiving reduced-dose prasugrel or ticagrelor than the clopidogrel-treated patients (VN: p = 0.000; MEA: p = 0.012; LTA: p = 0.002). Prasugrel resulted in significantly lower platelet inhibition than ticagrelor as determined by VN and LTA (VN: p = 0.000; LTA: p = 0.003). At three months, there was a significant overall difference in OPR among the three groups when measured by VN (p < 0.001), but not when measured by MEA (p = 0.596). OPR in the reduced-dose prasugrel group was not significantly different to the clopidogrel group at three months (VN: p = 0.180; MEA: p = 0.711). OPR in the reduced-dose ticagrelor group was similar to clopidogrel as determined by MEA at three months, but was different when assessed by VN (VN: p = 0.000; MEA: p = 0.540). Compared to standard-dose, the reduced-dose prasugrel OPR rate was significantly increased (VN: p = 0.008; MEA: p = 0.020).ConclusionsOPR values for reduced-dose prasugrel and conventional-dose clopidogrel at three months were similar but higher than for reduced-dose ticagrelor as determined by VN, but no differences were noted by MEA. The MEA assay might have less sensitivity and consistency than the VN assay. Further studies are needed to explore this discrepancy.

Project description:BackgroundHigh platelet reactivity (HPR) and low platelet reactivity (LPR) are associated with an increased risk of ischemic/bleeding events in patients undergoing percutaneous coronary intervention (PCI). The role platelet miRNAs carry out in platelet reactivity regulation is largely unknown.MethodsIn this study, we profiled the expression pattern of platelet miRNA in patients undergoing PCI with HPR (n=4) and LPR (n=4) by miRNA microarray screening. The candidate miRNAs were further validated in a larger sample of 17 LPR and 22 HPR patients by quantitative reverse-transcription polymerase chain reaction (RT-qPCR), and miR-15b was found differentially expressed. MiR-15b mimic and inhibitor were transfected into MEG-01 cells, then Bcl-2 protein expression and cell apoptosis were assessed. The relationship between platelet reactivity and platelet apoptosis was further evaluated. ABT-737, a Bcl-2 inhibitor was used to induce platelet apoptosis in PCI patients in vitro, and the influence of enhanced platelet apoptosis on platelet reactivity was explored.ResultsTwo miRNAs were found to be differentially expressed in patients with LPR and HPR using microarray system. Furthermore, the expression of miR-15b, a miRNA known to induce cell apoptosis via targeting of Bcl-2, was confirmed by RT-qPCR (P=0.020) to be 1.4× higher in the platelets of LPR patients than in those of HPR patients. Overexpression of miR-15b was demonstrated to suppress Bcl-2 protein expression and enhance cell apoptosis in a megakaryocyte cell line (MEG-01). The platelets of LPR patients expressed lower levels of Bcl-2 protein than those of HPR patients, and an inverse relationship between platelet reactivity and platelet apoptosis was observed among 44 patients who underwent PCI. Inducing platelet apoptosis in PCI patients in vitro, we observed that their platelet reactivity was decreased in a dose-dependent manner.ConclusionsThrough the promotion of platelet apoptosis, platelet miR-15b negatively regulates platelet reactivity in patients undergoing PCI. Platelet apoptosis may represent a novel antiplatelet target for overcoming HPR in PCI treatment.

Project description:BackgroundCilostazol overcomes high on-treatment platelet reactivity (HTPR) and reduces adverse cardiovascular (CV) outcomes after percutaneous coronary intervention (PCI). However, the role for triple antiplatelet therapy (TAPT) with cilostazol in addition to aspirin and clopidogrel after PCI is not well defined.MethodsWe conducted a MEDLINE/EMBASE/CENTRAL search for randomised trials, until May 2014, evaluating TAPT compared with dual antiplatelet therapy (DAPT) of aspirin and clopidogrel alone in patients undergoing PCI and reporting platelet reactivity and/or CV outcomes. The primary platelet reactivity outcome was differences in platelet reactivity unit (PRU) with secondary outcomes of %platelet inhibition and rate of HTPR. The primary CV outcome was major adverse cardiovascular events (MACE), with secondary outcomes of death, cardiovascular death, myocardial infarction, stent thrombosis (ST), target lesion revascularisation (TLR) and target vessel revascularisation (TVR) as well as safety outcomes of bleeding and drug discontinuations.ResultsIn 17 trials that evaluated platelet reactivity outcomes, the mean PRU value was 47.73 units lower with TAPT versus DAPT (95% CI -61.41 to -34.04, p<0.0001; mean PRU 182.90 vs 232.65). TAPT also increased platelet inhibition by 12.71% (95% CI 10.76 to 14.67, p<0.0001), and led to a 60% reduction in the risk of HTPR (relative risk=0.40; 95% CI 0.30 to 0.53) compared with DAPT. Moreover, among the 34 trials that evaluated CV outcomes, TAPT reduced the risk of MACE (incident rate ratio (IRR)=0.68; 95% CI 0.60 to 0.78), TLR (IRR=0.57; 95% CI 0.44 to 0.73), TVR (IRR=0.69; 95% CI 0.59 to 0.81) and ST (IRR=0.63; 95% CI 0.40 to 0.98) with no difference for other outcomes including bleeding, even in trials using drug-eluting stents. Drug discontinuation due to adverse effects was, however, higher with TAPT vs DAPT (IRR=1.59; 95% CI 1.32 to 1.91).ConclusionsIn patients undergoing PCI, addition of cilostazol to DAPT results in decreased platelet reactivity and a significant reduction in CV outcomes including ST, even in the drug-eluting stent era.

Project description:ImportanceAntithrombotic treatment in patients with atrial fibrillation (AF) and percutaneous coronary intervention (PCI) presents a balancing act with regard to bleeding and ischemic risks.ObjectivesTo evaluate the safety and efficacy of 4 antithrombotic regimens by conducting an up-to-date network meta-analysis and to identify the optimal treatment for patients with AF undergoing PCI.Data sourcesOnline computerized database (MEDLINE).Study selectionFive randomized studies were included (N?=?11?542; WOEST, PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, ENTRUST-AF PCI).Data extraction and synthesisThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used in this network meta-analysis, in which bayesian random-effects models were applied. The data were analyzed from September 9 to 29, 2019.Main outcomes and measuresThe primary safety outcome was thrombolysis in myocardial infarction (TIMI) major bleeding and the primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE).ResultsThe total number of participants included in the study was 11 532. The mean age of the participants ranged from 70 to 72 years, 69% to 83% were male, 20% to 26% were female, and the participants were predominantly white (>90%). Compared with vitamin K antagonists (VKA) plus dual antiplatelet therapy (DAPT) (reference), the odds ratios (ORs) (95% credible intervals) for TIMI major bleeding were 0.57 (0.31-1.00) for VKA plus P2Y12 inhibitor, 0.69 (0.40-1.16) for non-VKA oral anticoagulant (NOAC) plus DAPT, and 0.52 (0.35-0.79) for NOAC plus P2Y12 inhibitor. For MACE, using VKA plus DAPT as reference, the ORs (95% credible intervals) were 0.97 (0.64-1.42) for VKA plus P2Y12 inhibitor, 0.95 (0.64-1.39) for NOAC plus DAPT, and 1.03 (0.77-1.38) for NOAC plus P2Y12 inhibitor.Conclusions and relevanceThe findings of this study suggest that an antithrombotic regimen of VKA plus DAPT should generally be avoided, because regimens in which aspirin is discontinued may lead to lower bleeding risk and no difference in antithrombotic effectiveness. The use of a NOAC plus a P2Y12 inhibitor without aspirin may be the most favorable treatment option and the preferred antithrombotic regimen for most patients with AF undergoing PCI.

Dataset Information

An optimal window of platelet reactivity by LTA assay for patients undergoing percutaneous coronary intervention.

Objective

Design

Result

Conclusion

Trial registration

Publications

An optimal window of platelet reactivity by LTA assay for patients undergoing percutaneous coronary intervention.

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