038 Major bleeding still predicts death with a radial invasive strategy in NSTE-ACS: an analysis from theABOARD Study

AimWe sought to determine the incidence and type of major bleeding in moderate-to-high risk acute coronary syndromes (ACS) treated with intense antiplatelet therapy and systematic invasive strategy using predominantly the radial approach. We also examined whether these bleedings has an impact on mortality after multivariable adjustment.MethodsIn the multicenter randomized ABOARD study, 352 patients with acute coronary syndromes without ST-segment elevation were randomized for a “primary PCI” strategy or a strategy of intervention deferred to the next working day. No difference was observed in clinical outcomes between the two groups. Major bleeding complications (STEEPLE definitions) were correlated to 1 month mortality.ResultsPatients were treated by intense antiplatelet therapy: with a mean 660mg (±268) loading of clopidogrel and 111mg (±40) maintenance dose while 99% of the PCI patients receive abciximab the radial approach was predominant (84%).During the first 30 days major bleeding complications occurred in 19 patients (5.4%) with transfusion in 16 patients (4.5%). Occurrence of major bleeding did not differ between immediate and delayed intervention. The most frequent overt bleeding complications were from the gastrointestinal tract. The composite of GI bleeding and occult bleeding (loss of Hb of >3g/dL) represented n = 11 (57.9%) of all major bleeding complications. Major bleeding was associated with a significantly higher peak of creatinine during hospitalization 170.16 μmol/L ± 169.34 vs. 97.05 μmol/L ± 56.96 (p = 0.005) and a higher mortality rate 26.3% vs. 0.6%. After adjustment for all baseline characteristics, major bleeding was independently associated with an impressive increased hazard of death during the first 30 days (Odd ratio 75.7; 95% CI, 11.3 to 505.3; p<0.0001).ConclusionIn a population of radial catheterization for NSTEACS, GI bleeding is the most frequent bleeding complication. Despite the reduction of access site bleeding, major bleeding still remains a major independent predictor of mortality

High platelet reactivity in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Randomised controlled trial comparing prasugrel and clopidogrel

Background: Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited. Objectives: To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS). Patients: Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. “poor responders” were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors. Results: At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively. Conclusions: Routine platelet function testing identifies patients with high residual platelet reactivity (“poor responders”) on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit

P2Y12 platelet inhibition in clinical practice

Platelet adhesion, activation and aggregation play a pivotal role in atherothrombosis. Intracoronary atherothrombosis is the most common cause of the development of acute coronary syndrome (ACS), and plays a central role in complications occurring around percutaneous coronary intervention (PCI) including recurrent ACS, procedure-related myocardial infarction or stent thrombosis. Inhibition of platelet aggregation by medical treatment impairs formation and progression of thrombotic processes and is therefore of great importance in the prevention of complications after an ACS or around PCI. An essential part in the platelet activation process is the interaction of adenosine diphosphate (ADP) with the platelet P2Y12 receptor. The P2Y12 receptor is the predominant receptor involved in the ADP-stimulated activation of the glycoprotein IIb/IIIa receptor. Activation of the glycoprotein IIb/IIIa receptor results in enhanced platelet degranulation and thromboxane production, and prolonged platelet aggregation. The objectives of this review are to discuss the pharmacological limitations of the P2Y12 inhibitor clopidogrel, and describe the novel alternative P2Y12 inhibitors prasugrel and ticagrelor and the clinical implications of the introduction of these new medicines

Primary versus secondary source of data in observational studies and heterogeneity in meta-analyses of drug effects: a survey of major medical journals

The data from individual observational studies included in meta-analyses of drug effects are collected either from ad hoc methods (i.e. "primary data") or databases that were established for non-research purposes (i.e. "secondary data"). The use of secondary sources may be prone to measurement bias and confounding due to over-the-counter and out-of-pocket drug consumption, or non-adherence to treatment. In fact, it has been noted that failing to consider the origin of the data as a potential cause of heterogeneity may change the conclusions of a meta-analysis. We aimed to assess to what extent the origin of data is explored as a source of heterogeneity in meta-analyses of observational studies.publishe

Pre-treatment with P2Y 12

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the mainstay of treatment for acute coronary syndrome (ACS) patients, whether they undergo a percutaneous coronary intervention (PCI) or are managed medically. In recent years, the most appropriate timing for initiation and duration of P2Y12 receptor inhibition has been a focus of great interest. Many observational studies and a single prospective trial (CREDO) utilizing clopidogrel had focused on whether pre-treatment with clopidogrel, i.e. its administration upstream of coronary angiography and PCI, is beneficial. Although the rationale for pre-treatment is obvious, large-scale randomized trials supporting a pre-treatment strategy with clopidogrel or with the newer P2Y12 inhibitors prasugrel and ticagrelor did not exist. Proponents of a pre-treatment strategy had to rely on their best guess, on non-randomized studies, or on negative studies in which a trend for a benefit had been demonstrated. Recently, however, two randomized trials directly evaluated the value of pre-treatment-one in patients with a non-STE elevation myocardial infarction (NSTEMI)-the Comparison of Prasugrel at the Time of Percutaneous Coronary Intervention or as Pretreatment at the Time of Diagnosis in Patients with Non-ST Elevation Myocardial Infarction (ACCOAST) trial, and a second trial evaluating the use of ticagrelor in ST-elevation myocardial infarction (STEMI) patients, the Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST-elevation myocardial Infarction to open the Coronary artery (ATLANTIC) trial. Neither of the two trials, however, answered all the questions clinicians have about pre-treatment. And given the recent approval of the intravenous and rapidly acting P2Y12 inhibitor cangrelor, the choice of who should receive treatment with a P2Y12 inhibitor, which one should be used, and when it should be administered, should be carefully re-evaluated for all patients. This clinical review aims at evaluating the available evidence regarding the value of pre-treatment with the now four available oral and intravenous P2Y12 inhibitors that can be administered to patients in whom coronary angiography followed by a possible PCI is planned