Michael Gibson

Prognostic value of neutrophil/lymphocyte ratio in patients with ST-elevated myocardial infarction undergoing primary coronary intervention: A prospective, multicenter study

OBJECTIVEnThe pre-procedural neutrophil to lymphocyte ratio (N/L) is associated with adverse outcomes among patients with coronary artery disease but its prognostic value in ST-segment elevation myocardial infarction (STEMI) has not been fully investigated. This study evaluated the relations between pre-procedural N/L ratio and the in-hospital and long-term outcomes in STEMI patients undergoing primary percutaneous coronary intervention (PCI).nnnMETHODSnA total of 682 STEMI patients presented within the first 6h of symptom onset were enrolled and stratified according to tertiles of N/L ratio based on the blood samples obtained in the emergency room upon admission.nnnRESULTSnThe mean follow-up period was 43.3 months (1-131 months). In-hospital in-stent thrombosis, non-fatal myocardial infarction, and cardiovascular mortality increased as the N/L tertile ratio increased (p<0.001, p<0.001, p=0.003, respectively). Long-term in-stent thrombosis, non-fatal myocardial infarction and cardiovascular mortality also increased as the N/L ratio increased (p<0.001, p<0.001, p=0.002, respectively). On multivariate analysis, N/L ratio remained an independent predictor for both in-hospital (OR 1.189, 95% CI 1.000-1.339; p<0.001) and long-term major (OR 1.228, 95% CI 1.136-1.328; p<0.001) adverse cardiac events.nnnCONCLUSIONnThe N/L ratio was an independent predictor of both in-hospital and long-term adverse outcomes among STEMI patients undergoing primary PCI. Our findings suggest that this inexpensive, universally available hematological marker may be incorporated into the current established risk assessment model for STEMI.

Population pharmacokinetics and pharmacodynamics of rivaroxaban in patients with acute coronary syndromes

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTn• Population pharmacokinetics and pharmacodynamics of rivaroxaban have been characterized in healthy subjects and in patients with total venous thromboembolism, deep vein thrombosis or atrial fibrillation.nnnWHAT THIS STUDY ADDSn• This article is the first description of the population pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in patients with acute coronary syndrome (ACS). It is the largest population pharmacokinetic and pharmacodynamic study on rivaroxaban conducted to date (n= 2290). The PK and PK-PD relationship of rivaroxaban in patients with ACS were similar to those in other patient populations. In addition, model-based simulations showed that the influence of renal function and age on the exposure to rivaroxaban in the ACS population were similar to the findings from Phase 1 special population studies. These findings suggest that rivaroxaban has highly predictable PK-PD and may provide a consistent anticoagulant effect across the studied patient populations, which allows an accurate prediction of the dose to control anticoagulation optimally.nnnAIMSnThe aim of this analysis was to use a population approach to facilitate the understanding of the pharmacokinetics and pharmacodynamics of rivaroxaban in patients with acute coronary syndrome (ACS) and to evaluate the influence of patient covariates on the exposure of rivaroxaban in patients with ACS. METHODS A population pharmacokinetic model was developed using pharmacokinetic samples from 2290 patients in Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 46. The relationship between pharmacokinetics and the primary pharmacodynamic end point, prothrombin time, was evaluated.nnnRESULTSnThe pharmacokinetics of rivaroxaban in patients with ACS was adequately described by an oral one-compartment model. The estimated absorption rate, apparent clearance and volume of distribution were 1.24 h(-1) (interindividual variability, 139%), 6.48 l h(-1) (31%) and 57.9 l (10%), respectively. Simulations indicate that the influences of renal function, age and bodyweight on exposure in ACS patients are consistent with the findings in previous Phase 1 studies. Rivaroxaban plasma concentrations exhibit a close-to-linear relationship with prothrombin time in the ACS population, with little interindividual variability. The estimated pharmacokinetic and pharmacodynamic parameters for the ACS patients were comparable to those for venous thromboembolism prevention, deep vein thrombosis and atrial fibrillation patients.nnnCONCLUSIONSnThe similarity in pharmacokinetics/pharmacodynamics of rivaroxaban among different patient populations and the low interindividual variability in the exposure-prothrombin time relationship indicate that the anticoagulant effect of rivaroxaban is highly predictable and consistent across all the patient populations studied.

Underutilization of evidence-based medications in acute ST elevation myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) 9 Registry.

The TIMI 9 Registry set out to assess the management strategies and outcomes of an unselected group of patients with acute myocardial infarction presenting with ST segment elevation (STEMI). Demographic, procedural, and outcome data were collected from 840 consecutive patients with STEMI at 20 hospitals in United States and Canada between February and September 1994. Of them, 60% were treated with thrombolytic therapy, 9% with primary angioplasty, and 31% did not receive reperfusion therapy. Patients who did not receive reperfusion therapy were older, more likely female, and had a higher prevalence of prior myocardial infarction, congestive heart failure, higher Killip class on admission, and longer time from onset of symptoms to presentation. In evaluating the standard contraindications for fibrinolysis, approximately 10% in the thrombolytic group, 40% in the primary percutaneous coronary intervention (PCI), and 34% of those not receiving reperfusion therapy had at least one of these characteristics. Of those patients treated with fibrinolysis, only 20% met the National Heart Attack Alert Program goal of door-to-drug time < or =30 minutes. Likewise, of those treated with primary PCI, only 30% had PCI performed within < or =90 minutes. In-hospital mortality was significantly higher for patients not treated with reperfusion therapy (18.9%), compared with patients treated with fibrinolysis (7.6%) and those treated with primary PCI (10.5%) (P < 0.001). Thus, we found that reperfusion therapy was underused, with only 69% of patients with STEMI receiving this proven treatment, and of those only 25% treated within the recommended timeline. These data suggest that there is room for improvement in the management of these patients.

Does aspirin use prevent acute coronary syndrome in patients with pneumonia: multicenter prospective randomized trial.

ObjectivesThe aim of this study was to test the hypothesis that aspirin would reduce the risk for acute coronary syndromes (ACSs) in patients with pneumonia. BackgroundsPooled data suggest that pneumonia may trigger an ACS as a result of inflammatory reactions and the prothrombotic changes in patients with pneumonia. Hypothetically considering its antiaggregating and anti-inflammatory effects, aspirin might also be beneficial for the primary prevention of ACS in patients with pneumonia. MethodsOne hundred and eighty-five patients with pneumonia who had more than one risk factor for cardiovascular disease were randomized to an aspirin group (n=91) or a control group (n=94). The patients in the aspirin group received 300 mg of aspirin daily for 1 month. ECGs were recorded on admission and 48 h and 30 days after admission to assess silent ischemia. The level of high-sensitivity cardiac troponin T was measured on admission and 48 h after admission. The primary endpoint was the development of ACS within 1 month. The secondary endpoints included cardiovascular death and death from any cause within 1 month. ResultsThe &khgr;2-test showed that the rates of ACS at 1 month were 1.1% (n=1) in the aspirin group and 10.6% (n=10) in the control group (relative risk, 0.103; 95% confidence interval 0.005–0.746; P=0.015). Aspirin therapy was associated with a 9% absolute reduction in the risk for ACS. There was no significant decrease in the risk of death from any cause (P=0.151), but the aspirin group had a decreased risk of cardiovascular death (risk reduction: 0.04, P=0.044). ConclusionThis randomized open-label study shows that acetyl salicylic acid is beneficial in the reduction of ACS and cardiovascular mortality among patients with pneumonia.

A multicenter randomized study to evaluate intracoronary abciximab with the ClearWay catheter to improve outcomes with Lysis (IC ClearLy): trial study design and rationale.

Background Percutaneous coronary intervention (PCI) is a highly effective therapy for acute ST-elevation myocardial infarction. Adjunctive therapy with platelet glycoprotein (GP) IIb/IIIa inhibitor can result in increased vessel patency and improved outcomes in ST-elevation myocardial infarction patients undergoing PCI. The investigation of novel dosing and delivery strategies of this therapy may help to further improve outcomes. Methods IC-Clearly is a randomized, open-label, multicenter trial, with the purpose of evaluating the effectiveness of an intracoronary bolus dose of abciximab delivered using the ClearWay RX catheter vs. an intravenous bolus of abciximab for ST-elevation myocardial infarction with angiographically visible thrombus (thrombus grade ≥2). A total of 150 patients will be randomized 1: 1 to treatment of the culprit artery with intracoronary abciximab (75 patients) or intravenous abciximab (75 patients) in addition to a maintenance infusion regimen of abciximab administered intravenously for 12 h after PCI. The number of patients included in this study is based on the estimation of sample size needed to identify a statistically significant difference in the primary endpoints between the two groups. The primary endpoint chosen to evaluate this hypothesis is infarct size assessed by cardiac magnetic resonance. Clinical outcomes will be assessed for each patient through hospital discharge and at 30-day follow-up. Conclusion The purpose of this study is to evaluate whether an intracoronary bolus of abciximab delivered with the ClearWay RX catheter prior to the 12 h post-PCI intravenous infusion regimen of abciximab will result in significant additional clot resolution in vivo and improved myocardial perfusion when compared with an intravenous bolus of abciximab on top of the 12 h post-PCI intravenous infusion regimen of abciximab as per standard practice. The primary endpoint chosen to evaluate this hypothesis is infarct size as assessed by cardiac magnetic resonance.

Incidence, Patterns, and Associations Between Dual-Antiplatelet Therapy Cessation and Risk for Adverse Events Among Patients With and Without Diabetes Mellitus Receiving Drug-Eluting Stents: Results From the PARIS Registry

OBJECTIVESnThe aim of this study was to examine the frequency and clinical impact of different cessation patternsxa0ofxa0dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents among patients with and those without diabetes mellitus (DM).nnnBACKGROUNDnEarly DAPT suspension after percutaneous coronary intervention increases the risk for major adverse cardiac events. However, temporal variability in risk and relation to DAPT cessation patterns among patients with DM remain unclear.nnnMETHODSnUsing data from the PARIS (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients) registry, 1,430 patients with DM (34%) and 2,777 without DM (66%) treated with drug-eluting stents were identified. DAPT cessation modes were classified as temporary interruption (<14 days), disruption because of bleeding or poor compliance, and physician-recommended discontinuation.nnnRESULTSnDuring 2-year follow-up, DM was associated with an increased risk for thrombotic events but a similar risk for bleeding. The cumulative incidence of DAPT cessation was significantly lower in patients with versus those without DM (50.1% vs. 55.4%; pxa0< 0.01), driven largely by less frequent physician-guided discontinuation beyond 1 year. In contrast, 2-year rates of interruption and disruption were similar between groups. When DAPT was interrupted or discontinued under physician guidance, the risk for major adverse cardiac events was unchanged compared with patients with DM on uninterrupted DAPT. Conversely, when DAPT was disrupted, the risk for major adverse cardiac events increased compared with uninterrupted DAPT, regardless of diabetic status, with no evidence of statistical interaction.nnnCONCLUSIONSnDAPT cessation patterns vary according to diabetic status, with less frequent physician-guided discontinuation among patients with DM. The presence of DM does not emerge as a modifier of cardiovascular risk after DAPT cessation.

Impact of time-to-treatment on myocardial perfusion after primary percutaneous coronary intervention with Gp IIb-IIIa inhibitors.

Background Primary angioplasty has been shown to be superior to thrombolysis. However, previous reports have shown a negative impact of longer time-to-treatment on myocardial perfusion and survival even with mechanical reperfusion. However, these deleterious effects might potentially be overcome by an extensive use of glycoprotein (Gp) IIb–IIIa inhibitors. Thus, the aim of the current study was to evaluate the prognostic role of the interval from symptoms onset to reperfusion in a large cohort of patients undergoing primary angioplasty with Gp IIb–IIIa inhibitors. Methods Our population is represented by 1560 patients undergoing primary angioplasty for ST-segment elevation myocardial infarction (STEMI) included in the EGYPT (Early Glycoprotein IIb-IIIa Inhibitors in Primary Angiography) database. Myocardial perfusion was evaluated by angiography or ST-segment resolution, whereas infarct size was estimated by using peak creatine kinase and creatine kinase-MB (CK-MB). Follow-up data were collected between 30 days and 1 year after primary angioplasty. Results Time-to-treatment was significantly associated with age and female sex, diabetes and previous myocardial infarction (MI), but inversely related to smoking. Time-to-treatment affected the rate of postprocedural thrombolysis in myocardial infarction (TIMI) 3 flow (Pu200a<u200a0.0001), myocardial blush grade 2–3 (Pu200a=u200a0.052), complete ST-resolution (Pu200a<u200a0.0001) and distal embolization (Pu200a=u200a0.038). This relationship was confirmed after correction for baseline confounding factors for postprocedural TIMI 3 flow (Pu200a=u200a0.008) and complete ST-segment resolution (Pu200a=u200a0.003). Furthermore, time-to-treatment significantly affected enzymatic infarct size, even after correction for baseline confounding factors [odds ratio (OR) 95% confidence interval (95% CI)u200a=u200a1.002 (1.001–1.003), Pu200a=u200a0.004]. At 208u200a±u200a160 days follow-up, time-to-treatment was associated with a significantly higher mortality (Pu200a=u200a0.006). The impact was confirmed when time-to-treatment was evaluated as a continuous variable (Pu200a<u200a0.001), even after correction for baseline confounding factors [age, sex, diabetes, smoking, hypertension, previous myocardial infarction (MI), preprocedural TIMI 3 flow, multivessel disease, coronary stenting and early Gp IIb–IIIa inhibitors] (Pu200a=u200a0.001). Conclusion This study showed that time-to-treatment is a major determinant of mortality in ST-segment elevation myocardial infarction patients undergoing primary angioplasty. Impaired epicardial and myocardial perfusion and larger infarct size associated with longer ischemia time contribute to explain this finding.

Rationale and design of the AngeLmed for Early Recognition and Treatment of STEMI trial: A randomized, prospective clinical investigation

Significant improvements in door-to-balloon times have led to a reduction in mortality in ST-segment elevation myocardial infarction; however, mean symptom-to-door times remain at 2 to 3 hours. An intracardiac electrogram monitoring device may be beneficial in high-risk patients by alerting them to rapidly progressive ST-segment changes indicative of acute coronary occlusion. The Cardiosaver and DETECT phase I clinical studies demonstrated the safety, feasibility, and potential benefit of using an intracardiac electrogram monitoring device to alert the patient to seek medical attention. The goal of the randomized, prospective ALERTS Trial (Clinicaltrials.gov no. NCT00781118) is to evaluate the efficacy of an implantable monitoring device (IMD) in reducing the composite of either cardiac or unexplained death, new Q-wave myocardial infarction, or symptom-to-door time of >2 hours for confirmed thrombotic events. The IMD alerts the patient in real time when ST-segment deviation from a personalized baseline exceeds the trigger threshold. The trial is designed to enroll high-risk post-acute coronary syndrome patients or patients with previous multivessel coronary artery bypass surgery. All patients have the IMD implanted, with 1:1 unblinded randomization to the alerting feature being either turned on versus turned off for the first 6 months. Randomization occurs at the first follow-up visit, 7 to 14 days after the implantation of the IMD. Subjects then return for follow-up visits at months 1, 3, and 6 and thereafter every 6 months until closure of the investigational device exemption. Subjects who cannot be implanted successfully or who have the device explanted are removed from the study and followed up for a minimum of 30 days post-procedure. If a subject experiences a device-related complication and/or adverse experience, the subject is followed up until resolution or until the condition becomes stable and no further change is anticipated.

Impact of multivessel disease on myocardial perfusion and survival among patients undergoing primary percutaneous coronary intervention with glycoprotein IIb/IIIa inhibitors.

BACKGROUNDnAlthough primary angioplasty achieves thrombolysis in myocardial infarction (TIMI) 3 flow in most patients with ST-elevation myocardial infarction, epicardial recanalization does not guarantee optimal perfusion in a large proportion of patients. The influence of multivessel disease on myocardial reperfusion and survival after primary angioplasty has not been extensively investigated.nnnAIMnTo evaluate the impact of multivessel disease on myocardial perfusion and survival in a large cohort of patients with ST-elevation myocardial infarction treated with angioplasty and glycoprotein (GP) IIb/IIIa inhibitors.nnnMETHODSnThis analysis is based on 1494 patients undergoing primary angioplasty included in the EGYPT database. Myocardial perfusion was evaluated by angiography or ST-segment resolution, whereas infarct size was estimated by using peak creatine kinase-MB (CK-MB). Follow-up data were collected between 30 days and 1 year after primary angioplasty.nnnRESULTSnMultivessel disease was observed in 870 patients (58.2%). The extent of coronary artery disease was associated with age, diabetes, hypertension, previous myocardial infarction, previous revascularization, abciximab treatment and longer ischaemic time, and was independently associated with impaired angiographic myocardial perfusion (adjusted odds ratio 1.18, 95% confidence interval [CI] 1.01-1.40, P=0.049). At 208±160 days, the extent of coronary artery disease was independently associated with higher mortality (adjusted hazard ratio 1.54, 95% CI 1.06-2.24, P=0.022).nnnCONCLUSIONSnAmong patients with ST-elevation myocardial infarction undergoing primary angioplasty with GP IIb/IIIa inhibitor treatment, the extent of coronary artery disease was independently associated with impaired myocardial perfusion and survival.

Data on administration of cyclosporine, nicorandil, metoprolol on reperfusion related outcomes in ST-segment Elevation Myocardial Infarction treated with percutaneous coronary intervention

Mortality and morbidity in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) are still high [1]. A huge amount of the myocardial damage is related to the mitochondrial events happening during reperfusion [2]. Several drugs directly and indirectly targeting mitochondria have been administered at the time of the PCI and their effect on fatal (all-cause mortality, cardiovascular (CV) death) and non fatal (hospital readmission for heart failure (HF)) outcomes have been tested showing conflicting results [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. Data from 15 trials have been pooled with the aim to analyze the effect of drug administration versus placebo on outcome [17]. Subgroup analysis are here analyzed: considering only randomized clinical trial (RCT) on cyclosporine or nicorandil [3], [4], [5], [9], [10], [11], excluding a trial on metoprolol [12] and comparing trial with follow-up length <12 months versus those with longer follow-up [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. This article describes data related article titled “Clinical Benefit of Drugs Targeting Mitochondrial Function as an Adjunct to Reperfusion in ST-segment Elevation Myocardial Infarction: a Meta-Analysis of Randomized Clinical Trials” [17].