The net clinical benefit of personalized antiplatelet therapy in patients undergoing percutaneous coronary intervention.

This was a prospective study comparing two groups: personalized and non-personalized treatment with P2Y12 receptor blockers during a 12-month follow-up. We aimed to investigate whether personalized antiplatelet treatment in patients with high on-treatment platelet reactivity (HTPR) improves clinical outcome. Platelet reactivity was assessed by adenosine diphosphate induced aggregation using a multiple electrode aggregometry (MEA) in 798 patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). Patients with HTPR received up to four repeated loading doses of clopidogrel or prasugrel in the personalized treatment group (n=403), whereas no change in the treatment strategy was undertaken in patients with HTPR in the non-personalized treatment group (n=395). There were fewer major adverse cardiac events (MACE) in the personalized treatment group than in the non-personalized treatment group (7.4% compared with 15.3% respectively; P<0.001). The multivariate Cox regression analysis showed that the relative risk to develop MACE was 51% lower in the personalized treatment group as compared with the non-personalized treatment group [hazard ratio (HR)=0.49; 95% confidence interval (CI): 0.31-0.77; P<0.001]. Similarly, there was a clear net benefit of the personalized antiplatelet treatment over the non-personalized treatment (ischemic and bleedings events: 8.2% versus 18.7% respectively; HR=0.46; 95%CI: 0.29-0.70; P<0.001). Further analysis indicated that patients with aggregation values within the therapeutic window (21-49 units) experienced the lowest event rates (stent thrombosis and major bleeding: 2.5%) as compared with poor responders (≥50 units: 5.4%) or ultra-responders (0-20 units: 5.2%). In conclusion, personalized antiplatelet treatment might improve patients' outcome without increasing bleeding complications compared with the non-personalized treatment during a 12-month follow-up.

CLSI-Based Validation of Manufacturer-Derived Reference Intervals on the Cobas 8000 Platform.

BACKGROUND: Reference intervals provided by diagnostic test manufacturers should be transferred to clinical laboratories after validation. Although protocols exist, laboratories rarely perform and report on results of validation studies. METHODS: We validated reference intervals (RIs) of 87 analytes on a Cobas 8000 platform according to standards published by the Clinical and Laboratory Standards Institute (CLSI). RESULTS: For 8 analytes, decision limits were provided in the package inserts. Among the 79 RIs subjected to transference validation, 8 were found not valid for transference, including lactate dehydrogenase (LDH) among women, and the following among both sexes: potassium, homocysteine, immunoglobulin E (IgE), free lambda light chain (FLC λ), C3 complement (C3c), folate, and 25-hydroxy vitamin D (25[(OH]D). For LDH, potassium, homocysteine, C3c, folate, and 25(OH)D, RIs or thresholds suitable for transference were available in the literature; however, this was not the case for IgE and FLC λ. CONCLUSION: The present study demonstrates that validation of RIs provided in the manufacturer provided package inserts is indispensable.

Analytical and clinical performance of a new molecular assay for Epstein-Barr virus DNA quantitation.

Quantitation of EBV DNA has been shown to be a useful tool to identify and monitor patients with immunosuppression and high risk for EBV-associated disease. In this study, the analytical and clinical performance of the new Realquality RS-EBV Kit (AB Analitica, Padova, Italy) was investigated. The clinical performance was compared to that of the EBV R-gene (bioMerieux, Varilhes, France) assay. When the accuracy of the new assay was tested, all results except of one were found to be within ±0.5log10 unit of the expected panel results. Determination of linearity showed a quasilinear curve, the between day imprecision ranged from 18% to 88% and the within run imprecision from 16% to 53%. When 96 clinical EDTA whole blood samples were tested, 77 concordant and 19 discordant results were obtained. When the results for the 69 samples quantifiable with both assays were compared, the new assay revealed a mean 0.31log10 unit higher measurement. The new assay proved to be suitable for the detection and quantitation of EBV DNA in EDTA whole blood in the routine diagnostic laboratory. The variation between quantitative results obtained by the assays used in this study reinforces the use of calibrators traceable to the existing international WHO standard making different assays better comparable.

Individualising dual antiplatelet therapy after percutaneous coronary intervention: the IDEAL-PCI registry.

OBJECTIVE: To evaluate the clinical utility of individualising dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in an all-comers population, including ST-elevation myocardial infarction (STEMI) patients. SETTING: Tertiary care single centre registry. PARTICIPANTS: 1008 consecutive PCI patients with stent implantation, without exclusion criteria. INTERVENTION: Peri-interventional individualisation of DAPT, guided by multiple electrode aggregometry (MEA), to overcome high on-treatment platelet reactivity (HPR) to ADP-induced (≥50 U) and arachidonic acid (AA)-induced aggregation (>35 U). OUTCOME MEASURES: The primary efficacy end point was definite stent thrombosis (ST) at 30 days. The primary safety end point was thrombolysis in myocardial infarction (TIMI) major and minor bleeding. Secondary end points were probable ST, myocardial infarction, cardiovascular death and the combined end point: major cardiac adverse event (MACE). RESULTS: 53% of patients presented with acute coronary syndrome (9% STEMI, 44% non-ST-elevation). HPR to ADP after 600 mg clopidogrel loading occurred in 30% of patients (73±19 U vs 28±11 U; p<0.001) and was treated by prasugrel or ticagrelor (73%), or clopidogrel (27%) reloading (22±12 U; p<0.001). HPR to ADP after prasugrel loading occurred in 2% of patients (82±26 U vs 19±10 U; p<0.001) and was treated with ticagrelor (34±15 U; p=0.02). HPR to AA occurred in 9% of patients with a significant higher proportion in patients with HPR to ADP (22% vs 4%, p<0.001) and was treated with aspirin reloading. Definite ST occurred in 0.09% of patients (n=1); probable ST, myocardial infarction, cardiovascular death and MACE occurred in 0.19% (n=2), 0.09% (n=1) and 1.8% (n=18) of patients. TIMI major and minor bleeding did not differ between patients without HPR and individualised patients (2.6% for both). CONCLUSIONS: Individualisation of DAPT with MEA minimises early thrombotic events in an all-comers PCI population to an unreported degree without increasing bleeding. A randomised multicentre trial utilising MEA seems warranted. TRIAL REGISTRATION NUMBER: http://www.clinicaltrials.gov; NCT01515345.

Platelet inhibition by abciximab bolus-only administration and oral ADP receptor antagonist loading in acute coronary syndrome patients: the blocking and bridging strategy.

INTRODUCTION: Current guidelines still recommend the bolus and infusion administration of glycoprotein IIbIIIa inhibitors in patients with high-risk acute coronary syndrome undergoing percutaneous coronary intervention. We sought to evaluate the extent of platelet inhibition by a blocking and bridging strategy with intracoronary abciximab bolus-only administration and oral loading of adenosine diphosphate receptor antagonists. PATIENTS AND METHODS: Fifty-six consecutive high-risk acute coronary syndrome patients with bolus-only abciximab administration (0.25 mg/kg i.c.) and loading with 600 mg clopidogrel (55%) or 60 mg prasugrel (45%) were included in this study. Platelet aggregation induced by thrombin receptor-activating peptide and adenosine diphosphate was measured by multiple electrode aggregometry up to 7 days. RESULTS: Thrombin receptor-activating peptide induced platelet aggregation was significantly suppressed for a minimum of 48 h (45±17U) and returned to a normal range (>84 U) after 6 days (90±26U; p<0.001). Co-medication with prasugrel significantly reduced adenosine diphosphate-induced (p=0.002) and thrombin receptor-activating peptide-induced (p=0.02) platelet aggregation compared with clopidogrel throughout the observation period. No stent thrombosis or repeat myocardial infarction occurred at 30-day follow-up. CONCLUSIONS: Immediate blocking of platelet aggregation in high-risk acute coronary syndrome patients by intracoronary abciximab bolus-only administration and bridging to prolonged inhibition via oral blockade of ADP receptors effectively inhibited overall platelet reactivity for at least 48 h, questioning the value of continuous abciximab infusion. Co-medication with prasugrel vs. clopidogrel synergistically augmented platelet inhibition.