Current and Future Insights for Optimizing Antithrombotic Therapy to Reduce the Burden of Cardiovascular Ischemic Events in Patients with Acute Coronary Syndrome

The pharmacological treatment strategies for acute coronary syndrome (ACS) in recent years are constantly evolving to develop more potent antithrombotic agents, as reflected by the introduction of more novel P2Y12 receptor inhibitors and anticoagulants to reduce the ischemic risk among ACS patients. Despite the substantial improvements in the current antithrombotic regimen, a noticeable number of ACS patients continue to experience ischemic events. Providing effective ischemic risk reduction while balancing bleeding risk remains a clinical challenge. This updated review discusses the currently approved and widely used antithrombotic agents and explores newer antithrombotic treatment strategies under development for the initial phase of ACS

Efficacy and Safety of Glycoprotein IIb/IIIa Inhibitors on Top of Ticagrelor in STEMI: A Subanalysis of the ATLANTIC Trial

BACKGROUND: Glycoprotein IIb/IIIa inhibitors (GPIs) in combination with clopidogrel improve clinical outcome in ST-elevation myocardial infarction (STEMI); however, finding a balance that minimizes both thrombotic and bleeding risk remains fundamental. The efficacy and safety of GPI in addition to ticagrelor, a more potent P2Y12-inhibitor, have not been fully investigated. METHODS: 1,630 STEMI patients who underwent primary percutaneous coronary intervention (PCI) were analyzed in this subanalysis of the ATLANTIC trial. Patients were divided in three groups: no GPI, GPI administration routinely before primary PCI, and GPI administration in bailout situations. The primary efficacy outcome was a composite of death, myocardial infarction, urgent target revascularization, and definite stent thrombosis at 30 days. The safety outcome was non-coronary artery bypass graft (CABG)-related PLATO major bleeding at 30 days. RESULTS: Compared with no GPI (n\u2009=\u2009930), routine GPI (n\u2009=\u2009525) or bailout GPI (n\u2009=\u2009175) was not associated with an improved primary efficacy outcome (4.2% no GPI vs. 4.0% routine GPI vs. 6.9% bailout GPI; p\u2009=\u20090.58). After multivariate analysis, the use of GPI in bailout situations was associated with a higher incidence of non-CABG-related bleeding compared with no GPI (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.32-6.64; p\u2009=\u20090.03). However, routine GPI use compared with no GPI was not associated with a significant increase in bleeding (OR 1.78, 95% CI 0.88-3.61; p\u2009=\u20090.92). CONCLUSION: Use of GPIs in addition to ticagrelor in STEMI patients was not associated with an improvement in 30-day ischemic outcome. A significant increase in 30-day non-CABG-related PLATO major bleeding was seen in patients who received GPIs in a bailout situation

Flow cytometric analysis of viable bacteria in urine samples of febrile patients at the emergency department

BACKGROUND: Fast and reliable diagnostics are important in febrile patients admitted to the emergency department. Current urine diagnostics are fast but moderately reliable or reliable but time consuming. Flow cytometry (FC) is a new promising technique in the diagnostics of complicated urinary tract infections by counting bacteria in urine samples. The aim of this study is to improve the FC method by counting only viable bacteria. METHODS: Urine was obtained from 135 consecutive febrile patients at the emergency department. According to protocol regular diagnostic urine tests were performed. In addition, FC counting of viable and non-viable bacteria was executed after staining with thiazole orange and propidium iodide. All test results were compared to the results of urine culture (≥ 10(5) colony forming units/mL). RESULTS: At a cut-off value of 2.01 x 10(5) viable bacteria/mL the sensitivity was 100% and specificity was 78.4% (AUC-value 0.955 on ROC-curve). Spearman correlation test exhibited a higher correlation for flow cytometric counting of only viable bacteria than counting of all bacteria (0.59 vs. 0.37). Using ROC-curves, the AUC-values for FC counting of all bacteria, only viable bacteria and Gram staining were respectively 0.935, 0.955 and 0.968 (p>0.05). CONCLUSION: FC counting of only viable bacteria can predict quickly and reliably positive and negative urine cultures in febrile patients admitted to the emergency department. It can help to improve the speed and accuracy of the diagnostic procedure at the emergency department. This article is protected by copyright. All rights reserved

A randomised, investigator-initiated, clinical trial of the effects of fentanyl on P2Y12-receptor inhibition in patients with ST-elevation myocardial infarction who are pre-treated with crushed ticagrelor:rationale and design of the Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME3) trial

BackgroundFast and accurate platelet inhibition is an important therapeutic goal in the acute treatment of patients with ST-elevation myocardial infarction (STEMI). Platelet inhibitory effects induced by oral P2Y12-receptor antagonists are delayed in STEMI patients undergoing primary percutaneous coronary intervention (PCI) due to haemodynamic changes and delayed gastro-intestinal absorption. Concomitant use of opioids, although recommended in the American College of Cardiology/American Heart Association and European Society of Cardiology STEMI guidelines, further delays gastro-intestinal absorption. To date, trials investigating alternative analgesics in STEMI patients have been scarce. This trial aims to assess the feasibility of anovel drug strategy for treatment of STEMI patients with crushed ticagrelor in combination with paracetamol (acetaminophen) instead of opioids.HypothesisSTEMI patients who are pre-treated with crushed ticagrelor and paracetamol have ahigher level of platelet inhibition after primary PCI than patients pre-treated with crushed ticagrelor and fentanyl.Study designThe Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME3) trial is arandomised controlled trial designed to examine whether administration of paracetamol instead of fentanyl can optimise platelet inhibition in STEMI patients who are pre-treated with crushed ticagrelor in the ambulance. One hundred and ninety patients with STEMI will be randomised (1:1fashion) to intravenous (IV) fentanyl or IV paracetamol. The primary endpoint is the level of platelet reactivity units measured immediately after primary PCI.SummaryThe ON-TIME3 trial (NCT03400267) aims to achieve optimal platelet inhibition and pain relief in STEMI patients receiving crushed ticagrelor in the ambulance by investigating IVfentanyl and IVparacetamol as analgesics

Feasibility and safety of cangrelor in patients with suboptimal P2Y(12) inhibition undergoing percutaneous coronary intervention:rationale of the Dutch Cangrelor Registry

Abstract Background Despite the advances of potent oral P2Y12 inhibitors, their onset of action is delayed, which might have a negative impact on clinical outcome in patients undergoing percutaneous coronary intervention (PCI). Trials conducted in the United States of America have identified cangrelor as a potent and rapid-acting intravenous P2Y12 inhibitor, which has the potential of reducing ischemic events in these patients without an increase in the bleeding. As cangrelor is rarely used in The Netherlands, we conducted a nationwide registry to provide an insight into the use of cangrelor in the management of patients with suboptimal platelet inhibition undergoing (primary) PCI (the Dutch Cangrelor Registry). Study design The Cangrelor Registry is a prospective, observational, multicenter, single-arm registry with cangrelor administered pre-PCI in: (1) P2Y12 naive patients with ad-hoc PCI, (2) patients with STEMI/NSTEMI with suboptimal P2Y12 inhibition including (3) stable resuscitated/defibrillated patients with out-of-hospital cardiac arrest (OHCA) due to acute ischemia and (4) STEMI/NSTEMI patients with a high thrombotic burden. Primary endpoint is 48 h Net Adverse Clinical Events (NACE), which is a composite endpoint of all-cause death, recurrent myocardial infarction (MI), target vessel revascularization (TVR), stroke, stent thrombosis (ST) and BARC 2-3-5 bleeding. Summary The Dutch Cangrelor Registry will assess the feasibility and safety of cangrelor in patients with suboptimal P2Y12 inhibition undergoing (primary) PCI in the setting of acute coronary syndrome (ACS) and stable coronary artery disease (CAD) in the Netherlands

Guided and unguided de-escalation from potent P2Y(12) inhibitors among patients with acute coronary syndrome:a meta-analysis

AIM: Optimal dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) intends to balance ischemic and bleeding risks. Various DAPT de-escalation strategies, defined as switching from a full-dose potent to a reduced dose or less potent P2Y12 inhibitor, have been evaluated in several ACS-PCI trials. We aimed to compare DAPT de-escalation to standard DAPT with full dose potent P2Y12 inhibitors in ACS patients who underwent PCI. METHODS & RESULTS: PubMed, Google Scholar and Cochrane Central Register of Controlled Trials were searched for eligible randomised controlled trials. Aspirin monotherapy trials were excluded. Five randomised trials (n = 10,779 patients) that assigned DAPT de-escalation (genetically guided to clopidogrel n = 1,242; platelet function guided to clopidogrel n = 1,304; unguided to clopidogrel n = 1,672; unguided to lower dose n = 1,170) versus standard DAPT (control group n = 5,391) were included in this analysis. DAPT de-escalation was associated with a significant reduction in Bleeding Academic Research Consortium ≥ 2 bleeding (HR 0.57, 95% CI 0.42-0.78; I2 = 77%) as well as major adverse cardiac events, represented in most trials by the composite of cardiovascular mortality, myocardial infarction, stent thrombosis and stroke (HR 0.77, 95% CI 0.62-0.96; I2 = 0%). Notwithstanding the limited power, consistency was noted across various de-escalation strategies. CONCLUSION: De-escalation of DAPT after PCI for ACS, both unguided and guided by genetic or platelet function testing, was associated with lower rates of clinically relevant bleeding and ischemic events as compared to standard DAPT with potent P2Y12 inhibitors based on five open-label RCTs reviewed