Elevated serum transaminases in patients with acute coronary syndromes: Do we need a revision of exclusion criteria for clinical trials?

BACKGROUND: Elevations of hepatic transaminase (serum alanine transaminase [ALT] and serum aspartate aminotransferase [AST]) levels in patients with acute coronary syndrome (ACS), although transient, may result in exclusions from clinical efficacy trials due to suspected liver disease. The aim of this study was to evaluate the concentrations of serum transaminases in ACS and relate these to currently accepted AST/ALT exclusion criteria from clinical trials. METHODS: One hundred consecutive patients with ACS were prospectively examined. Blood samples for AST, ALT, total bilirubin and troponin I concentration were obtained at the time of admission and after 6, 12 and 24 hours. RESULTS: Eighty percent of patients had elevated AST, and 47% ALT; 43% of patients characterized AST concentration > 3 × upper limit of normal (ULN) in at least one measurement, while 8% of patients presented ALT concentration > 3 × ULN. AST presented higher concentrations when compared to ALT, resulting in a high De-Ritis ratio at every time point. No significant or high correlations were found between the concentrations of serum transaminases, De-Ritis ratio and troponin I. Two different cut-off values of troponin I were adopted to define the amount of infarcted myocardium that distinguished 28-31% of individuals with "large infarction". Among these patients, approximately 93% presented AST concentrations > 3 × ULN. CONCLUSIONS: Hepatic transaminases are often elevated in ACS, with the majority of patients with more extensive myocardial injury presenting high concentrations of AST. In the setting of ACS, current transaminase thresholds for liver dysfunction used in clinical trials may lead to excessive and inadequate exclusions of patients with larger infarcts from such trials.

Effect of Low High-Density Lipoprotein Level on Endothelial Activation and Prothrombotic Processes in Coronary Artery Disease-A Pilot Study.

High-density lipoproteins (HDL) play an important role in the prevention of atherosclerosis. The aim of the study was to assess the relationship between serum HDL-C concentration and proinflammatory/prothrombic activation in coronary artery disease (CAD) patients. The study group included 27 acute myocardial infarction (AMI) patients and 30 stable angina pectoris (SA) patients. The control group consisted of 23 people without cardiac symptoms. In the AMI and SA groups, a lower HDL-C and a higher LDL-C/HDL-C index were observed. The SA patients had lower total cholesterol, LDL-C, sE-selectin ligand, as well as higher triglycerides and CD40 concentration in comparison with both the control and AMI groups. A higher von Willebrand Factor and intercellular adhesion molecule-1 were found in both study groups. Low HDL-C concentration in the CAD patients may intensify pro-inflammatory endothelial activation and prothrombotic processes. A low concentration of HDL-C and a high value of the LDL-C/HDL-C index seem to be better indices of atherogenic processes than the LDL-C concentration alone.

Low dose of ROSuvastatin in combination with EZEtimibe effectively and permanently reduce low density lipoprotein cholesterol concentration independently of timing of administration (ROSEZE): A randomized, crossover study - preliminary results.

BACKGROUND: In an attempt to improve low density lipoprotein-cholesterol (LDL-C) level control in patients ineffectively treated with statins, we evaluated the effectiveness of a fixed-dose combination (FDC) of 10 mg rosuvastatin and ezetimibe and its relation to the timing of drug administration. METHODS: A randomized, open label, single center, crossover study involving 83 patients with coronary artery disease and hypercholesterolemia with baseline LDL-C ≥ 70 mg/dL. In arm I the FDC drug was administered in the morning for 6 weeks, then in the evening for the following 6 weeks and vice versa in arm II. The primary endpoint was the change in LDL-C after 6 and 12 weeks. RESULTS: The median LDL-C concentration at baseline, after 6 and 12 weeks respectively was: 98.10 mg/dL (Q1;Q3: 85.10;116.80), 63.14 mg/dL (50.70;77.10) and 59.40 mg/dL (49.00;73.30); p < 0.001. LDL-C levels were similar regardless of the timing of drug administration (morning 62.50 mg/dL [50.70;76.00] vs. evening 59.70 mg/dL [48.20;73.80]; p = 0.259], in both time points: 6 week: 63.15 mg/dL (50.75;80.65) vs. 63.40 mg/dL (50.60;74.00), p = 0.775; and 12 week: 62.00 mg/dL (50.20;74.40) vs. 59.05 mg/dL (47.65;66.05), p = 0.362. The absolute change in LDL-C concentration for the morning vs. evening drug administration was - 6 week: -34.6 mg/dL (-56.55; -19.85) (-34.87%) vs. -31.10 mg/dL (-44.20; -16.00) (-35.87%) (p not significant); 12. week: -34.20 mg/dL (-47.8; -19.0) (-37.12%) vs. -37.20 mg/dL (-65.55; -23.85) (-40.06%) (p not significant). The therapy was safe and well tolerated. CONCLUSIONS: Fixed-dose combination of rosuvastatin and ezetimibe significantly and permanently decreases LDL-C regardless of the timing of drug administration.

Adherence to treatment assessed with the Adherence in Chronic Diseases Scale in patients after myocardial infarction.

INTRODUCTION: A substantial subset of patients after myocardial infarction (MI) discontinue pivotal medication early after discharge. In particular, cessation of antiplatelet treatment may lead to catastrophic ischemic events. Thus, adherence to prescribed medication in patients after MI is an issue of medical and social concern. PURPOSE: The aim of the study was to evaluate the level of adherence to treatment using a newly developed scale in patients after MI treated with percutaneous coronary intervention. PATIENTS AND METHODS: A single-center, prospective, observational cohort clinical study with a 6-month follow-up was performed. Patients with physical or cognitive impairment, prisoners, soldiers, and family members and coworkers of the researchers were excluded from the study. The impact of selected sociodemographic and clinical factors on adherence was evaluated in 221 patients (63 women and 158 men) aged 30 to 91 years. RESULTS: The results obtained with the Adherence in Chronic Diseases Scale (ACDS) ranged from 7 to 28 points; with the average and median scored being 23.35 and 24, respectively. The ACDS score reflects the level of adherence to prescribed medication. The high ACDS scores (>26 points) were obtained in 59 (26.7%) patients, intermediate scores (21-26 points) in 110 (49.8%) and low scores (<21 points) in 52 subjects (23.5%). Acute coronary syndrome (re-ACS) occurred in 18 (8.1%) patients during the follow-up period. The high-level adherence (ACDS score >26 points) was found in 11.1% of patients with re-ACS vs 28.4% of the remaining ones (P=0.1). Lower scores (mean ± standard deviation) in re-ACS patients were found for items 2 and 3 of the ACDS: 3.11±0.68 vs 3.45±0.73 (P=0.02) and 3.28±0.89 vs 3.64±0.64 (P=0.04), respectively. CONCLUSION: Age and previous MI were found to be independent factors influencing adherence assessed with the ACDS.

The impact of the time of drug administration on the effectiveness of combined treatment of hypercholesterolemia with Rosuvastatin and Ezetimibe (RosEze): study protocol for a randomized controlled trial.

BACKGROUND: Hypercholesterolemia is one of the main risk factors for cardiovascular disease. The first line treatment for hypercholesterolemia is statin therapy. When the expected low-density lipoprotein cholesterol (LDL-C) concentration is not achieved, the pharmacotherapy may be extended by combining the statin with the cholesterol absorption inhibitor ezetimibe. METHODS/DESIGN: The study is designed as a randomized, open-label, single-center, crossover study evaluating the effectiveness of combined therapy with rosuvastatin and ezetimibe for hypercholesterolemia. The study is planned to include 200 patients with hypercholesterolemia ineffectively treated with statins for at least 6 weeks. After enrollment participants are randomized into one of two arms receiving rosuvastatin and ezetimibe. In the first arm the study drug is administered in the morning (8:00 am) for 6 weeks and then in the evening for the next 6 weeks; in the second arm the study drug is administered at first in the evening (8:00 pm) for the first 6 weeks and then in the morning for the following 6 weeks. In order to minimize non-adherence to the treatment, all patients will receive the study drug free of charge. The primary outcome of the study is change in LDL-C at 6 and 12 weeks of the treatment, depending on the time of day of study drug administration. The secondary endpoints include change in total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoproteins ApoB and Apo AI, non-HDL cholesterol, small, dense (sd)-LDL cholesterol, lipoprotein(a), glucose, glycated hemoglobin, high-sensitivity C-reactive protein, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, and creatine kinase at 6 and 12 weeks of the study drug treatment, as well as assessment of plasma fluorescence using stationary and time-resolved fluorescence spectroscopy at baseline and at 6 and 12 weeks of the therapy. DISCUSSION: The RosEze trial is expected to demonstrate whether there is a significant difference in the effectiveness of the lipid-lowering therapy in reducing the concentration of cholesterol when the medications are taken in the morning compared with the evening time of day. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02772640 . Registered on 28 March 2016.

Comparison of Ticagrelor Pharmacokinetics and Pharmacodynamics in STEMI and NSTEMI Patients (PINPOINT): protocol for a prospective, observational, single-centre study.

INTRODUCTION: The most common classification of acute myocardial infarction (AMI) is based on electrocardiographic findings and distinguishes ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). Both types of AMI differ concerning their epidemiology, clinical approach and early outcomes. Ticagrelor is a P2Y12 receptor inhibitor, constituting the first-line treatment for STEMI and NSTEMI. According to available data, STEMI may be associated with lower plasma concentration of ticagrelor in the first hours of AMI, but currently there are no studies directly comparing ticagrelor pharmacokinetics or antiplatelet effect in patients with STEMI versus NSTEMI. METHODS AND ANALYSIS: The PINPOINT study is a phase IV, single-centre, investigator-initiated, prospective, observational study designed to compare the pharmacokinetics and pharmacodynamics of ticagrelor in patients with STEMI and NSTEMI assigned to the invasive strategy of treatment. Based on an internal pilot study, the trial is expected to include at least 23 patients with each AMI type. All subjects will receive a 180 mg loading dose of ticagrelor. The primary end point of the study is the area under the plasma concentration-time curve (AUC(0-6)) for ticagrelor during the first 6 hours after the loading dose. Secondary end points include various pharmacokinetic features of ticagrelor and its active metabolite (AR-C124910XX), and evaluation of platelet reactivity by the vasodilator-stimulated phosphoprotein assay and multiple electrode aggregometry. Blood samples for the pharmacokinetic and pharmacodynamic assessment will be obtained at pretreatment, 30 min, 1, 2, 3, 4, 6 and 12 hours post-ticagrelor loading dose. ETHICS AND DISSEMINATION: The study received approval from the Local Ethics Committee (Komisja Bioetyczna Uniwersytetu Mikolaja Kopernika w Toruniu przy Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy; approval reference number KB 617/2015). The study results will be disseminated through conference presentations and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02602444; Pre-results.

Adherence to antiplatelet treatment with P2Y12 receptor inhibitors. Is there anything we can do to improve it? A systematic review of randomized trials.

Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndromes (ACS) and/or undergoing percutaneous coronary interventions. Non-adherence to medication after ACS may lead to increased morbidity, mortality, and costs to the healthcare system due to elevated risk of stent thrombosis, myocardial infarction or death. Medication adherence is an issue of growing concern regarding the improvement of health system performance. Promoting medication adherence offers a rare opportunity to simultaneously improve health outcomes while reducing costs of treatment in patients with coronary artery disease (CAD). The aim of this systematic review was to critically discuss adherence to antiplatelet treatment with P2Y12 receptor inhibitors in CAD patients. After a systematic investigation of the literature in databases including PubMed, CENTRAL and Google Scholar, using appropriate keywords, and considering clinical randomized, prospective observational and retrospective studies, reporting on adherence to treatment with inhibitors of P2Y12 platelet receptors or educational interventions aimed to improve medication adherence in patients with CAD, seven articles were considered eligible for inclusion in this systematic review. Reported adherence to clopidogrel, despite catastrophic consequences of its premature discontinuation, is low. We identified several determinants of low adherence and early discontinuation of clopidogrel. We also present data on the usefulness, utilization and credibility of different methods of medication adherence assessment, and suggest and critically discuss available interventions aimed at improvement of adherence to clopidogrel, still showing the need for innovative approaches to achieve enhanced medication adherence and improve health outcomes after acute myocardial infarction.

Prediction of high risk of non-adherence to antiplatelet treatment.

BACKGROUND: Dual antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel is the standard of care for secondary prevention. Premature discontinuation of clopidogrel is associated with an increased risk of myocardial infarction (MI) or death, and greater health care expenditure. AIM: To develop an objective method for identification of patients with high risk of non-adherence to clopidogrel after MI. METHODS: A total of 189 patients were enrolled into a prospective, observational, single-centre study with a nine-month follow-up. Patients received a 600-mg loading dose and 75-mg maintenance dose of clopidogrel in combination with ASA doses of 300 mg and 75 mg, respectively. Adenosine diposphate-induced platelet aggregation (ADP-PA) was assessed during baseline hospitalisation and at three, six, and nine months after discharge. Adherence to medication with clopidogrel was defined as the proportion of drug availability based on data from the National Health Fund regarding prescribed drug purchases. Adherence was arbitrarily judged adequate when the proportion exceeded 80%. RESULTS: According to our hypothesis, ADP-PA in non-adherent patients should be higher at follow-up visits (at least once) as compared with measurement at hospitalisation. Based on the ROC curve analysis, the optimal cut-off point equal to 4 U was defined (p < 0.0001, 95% CI 0.562-0.654; sensitivity: 60.6%, specificity: 57.1%, positive predictive value: 63.3%, negative predictive value: 54.2%). The prevalence of true adherence to medication in groups of high and low probability of adherence defined according to developed criteria amounted 60 (50.8%) and 23 (32.4%) cases, respectively (p = 0.01). CONCLUSIONS: The newly developed method of objective identification of patients with high risk of non-adherence to clopidogrel after MI is easily applicable and cheap, and, despite relatively low sensitivity and specificity, it efficiently differentiates patients with regard to clinical end-points during follow-up.

Acetylsalicylic acid resistance risk factors in patients with myocardial infarction.

BACKGROUND: Despite its commonly recognized benefits in the cardiovascular disease setting, an issue of resistance to this drug has lately emerged. The aim of this research was assessment of the phenomenon of acetylsalicylic acid (ASA) resistance and its risk factors in patients treated for myocardial infarction. METHODS: This study is a post-hoc analysis of a previous prospective study with approximately 200 patients treated for myocardial infarction with a coated formulation of ASA. The population was divided into two subgroups according to the response to ASA. ASA responsiveness was assessed using the arachidonic acid-dependent platelet aggregation (ASPI-test). The measurements were performed using the technique of impedance aggregometry. RESULTS: The prevalence of aspirin resistance among the study population was 6.2%. All analyzed aggregometric parameters (including ASPI-test, adenosine diphosphate dependent platelet aggregation - ADP-test, bleeding time measurement) showed significant differences between both subgroups. ASA resistant patients had higher concentrations of brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hs-CRP), leukocytes (WBC) and platelets (PLT) but lower concentrations of hemoglobin (HGB). The temporal point analysis for both subgroups showed aspirin resistance incidence peak in patients at 9 months after myocardial infarction. CONCLUSIONS: The prevalence of aspirin resistance in our study population is comparable with rates reported in literature among patients with cardiovascular diseases. There is a possible relation between aspirin resistance and clopidogrel resistance. Presence did not affect the incidence of the clinical end-points.

Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients with Acute Myocardial Infarction (IMPRESSION): study protocol for a randomized controlled trial.

BACKGROUND: Ticagrelor is an oral platelet P2Y12 receptor antagonist which is recommended for patients suffering from myocardial infarction, both with and without persistent ST segment elevation. Morphine is the first choice drug in pain alleviation in the same clinical subset. Recently a possible negative influence of morphine on the pharmacokinetics and antiplatelet effects of P2Y12 receptor blockers has been postulated. METHODS/DESIGN: The IMPRESSION study is a phase IV, single center, randomized, double-blind, placebo-controlled clinical trial that is designed to assess the influence of morphine on the pharmacokinetics and pharmacodynamics of ticagrelor in patients with myocardial infarction. The study is planned to include up to 100 patients with myocardial infarction who will be randomized into one of two arms in a 1:1 ratio. Subjects in the intervention arm prior to the loading dose of ticagrelor (180 mg) will receive morphine (5 mg) intravenously, whereas patients in the control arm will receive a placebo prior to the loading dose of ticagrelor (180 mg). The pharmacokinetics of ticagrelor and its active metabolite (AR-C124910XX) will be assessed by liquid chromatography mass spectrometry. Platelet function testing in each patient will be performed using up to four different methods (platelet vasodilator-stimulated phosphoprotein assay, multiple electrode aggregometry, VerifyNow, and light transmission aggregometry). DISCUSSION: This study is expected to provide essential evidence-based data on the impact of morphine on the absorption of ticagrelor in patients with myocardial infarction as well as to shed some light on the suspected connection between morphine use and antiplatelet activity of ticagrelor in the same group of patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02217878 (14 August 2014).

Discrepancies in assessment of adherence to antiplatelet treatment after myocardial infarction.

The poor response to clopidogrel is multifactorial and includes, amongst others, low patient adherence to medication. The aim of this study was to assess the reported patient adherence to treatment with clopidogrel and confront it with adherence assessed by drug availability. We evaluated determinants of adherence and its impact on platelet aggregation and clinical outcome. The study population comprised 184 patients treated with primary percutaneous coronary intervention for acute myocardial infarction. Follow-up visits were scheduled at 3, 6 and 9 months after discharge. Patient adherence to clopidogrel was defined according to self-reported drug intake and verified based on data from the National Health Fund regarding the purchase of prescribed drugs. The patients were judged as adherent when the proportion of drug availability exceeded 80%. According to drug availability, 100 (54.3%) patients were adherent and 84 (45.7%) were nonadherent. The analysis identified the following factors as predictors of low adherence (<80%): adenosine diphosphate-induced platelet aggregation (ADP-PA) during hospitalization ≤45 U, male gender and occurrence of ST-elevation myocardial infarction [(STEMI) vs. non-STEMI (NSTEMI)], while three-vessel disease was predictive of high adherence to medication. Compared with drug availability-based assessment, self-reported drug intake was significantly different: 172 (94.5%) patients reported regular and 10 (5.5%) patients reported irregular intake of clopidogrel. Clinical follow-up suggested that the self-reported nonregular clopidogrel intake may discriminate patients with a high risk of cardiovascular events. We demonstrated a huge discrepancy between the two most widely used methods for the evaluation of adherence to clopidogrel in secondary prevention treatment in patients after STEMI and NSTEMI. ADP-PA during hospitalization ≤45 U, male gender and STEMI (vs. NSTEMI) were independent predictors of nonadherence while three-vessel disease was independently predictive of adherence to treatment with clopidogrel in the investigated population.

Time-related changes in determinants of antiplatelet effect of clopidogrel in patients after myocardial infarction.

Substantial variability of antiplatelet action is an important limitation of clopidogrel. The aim of this study was to evaluate time-related changes in determinants of clopidogrel responsiveness in patients after myocardial infarction. The study population comprised 191 consecutive patients treated with primary percutaneous coronary intervention for acute myocardial infarction. Follow-up visits were scheduled at 3, 6 and 9 months after discharge. ADP-induced platelet aggregation was tested with Multiplate Analyzer. Patients with ADP-PA>46.8U were defined as clopidogrel non-responders. The prevalence of clopidogrel non-responsiveness was highest during hospitalization and at 9 month follow-up visit, while it was lowest at 3 and 6 months after myocardial infarction (P=0.004). According to multivariate analysis, platelet count, mean platelet volume, concentration of hsCRP and leukocyte count influenced ADP-induced platelet aggregation in multiple assessment points. BMI, concentrations of hemoglobin, glycated hemoglobin, and BNP, hematocrit, adherence to medication, and patient׳s age were found to be independent predictors of high on-treatment ADP-induced platelet aggregation only at a single follow-up visit. Determinants of clopidogrel responsiveness in patients after myocardial infarction change within the long-term therapy. During hospitalization and early after discharge only biological factors affect ADP-induced platelet aggregation, while non-adherence to antiplatelet therapy may be a significant factor in determining clopidogrel non-responsiveness during late follow-up visits.

Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of acute coronary syndrome and maintains its antiplatelet potency at 30-day follow-up.

BACKGROUND: The aim of this study was to assess antiplatelet effect of prasugrel in acute coronary syndrome (ACS) patients with high on-treatment platelet reactivity (HTPR) on clopidogrel, undergoing percutaneous coronary intervention (PCI). METHODS: A prospective, platelet reactivity-guided, parallel-group, open-label study including 71 patients pretreated with clopidogrel 600 mg and assigned either to prasugrel (30 mg loading dose, 10 mg maintenance dose; n = 46) or clopidogrel (150 mg maintenance dose for 6 days and thereafter 75 mg maintenance dose; n = 25) regimen, based on vasodilator-stimulated phosphoprotein (VASP)-assessed platelet reactivity index (PRI; > 50% vs. ≤ 50%) measured next morning post-PCI. RESULTS: Median PRI value after switch to prasugrel sharply declined at 24 h (70.0 [61.3-75.6] vs. 11.9 [6.8-25.7]%; p < 0.000001) and slightly but significantly rose between 24 h and 30 days (27.9 [15.5-46.8]%; p < 0.0006). In contrast, median PRI values in the clopidogrel group were similar at baseline and at 24 h (25.1 [13.7-40.2] vs. 22.0 [18.4-36.8]%; p = NS) and then modestly rose at 30 days (30.3 [20.4-45.7]%; p < 0.03). The prevalence of HTPR decreased in the prasugrel group between baseline and 24 h measurements (100.0 vs. 4.3%; p < 0.0001). Rates of patients with HTPR at 24 h and 30 days were similar in both groups, so were the tendencies in patterns of platelet inhibition evaluated with multiple electrode aggregometry as compared with the VASP assay. CONCLUSIONS: Our study indicates that prasugrel overcomes HTPR on clopidogrel in the acute phase of interventionally treated ACS and maintains its antiplatelet potency in 30-day follow-up. Potential clinical benefits of personalized antiplatelet prasugrel-based therapy warrant further investigation in clinical ACS trials.

Low-dose of oral factor Xa inhibitors in patients with a recent acute coronary syndrome: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Recently, randomized controlled trials (RCTs) have shown that therapy with new oral activated factor X (Xa) inhibitors in acute coronary syndrome (ACS) yielded a reduction of ischemic events. However, this therapy was associated with a dose-related increase in major bleeding complications. We aimed to perform a systematic review and meta-analysis to appraise the clinical efficacy and safety of the lowest doses of oral factor Xa inhibitors compared with placebo in patients after a recent ACS. METHODS: The primary endpoint was cardiovascular mortality. The rate of new myocardial infarction (MI) was the secondary efficacy endpoint, whereas major bleeding complications were recorded as a safety endpoint. Five RCTs were included in the meta-analysis enrolling a total of 25,643 patients. RESULTS: There was no significant difference in mortality between patients treated with new antithrombotics compared with those receiving the standard therapy: odds ratio (OR), [95% confidence interval (CI)] = 0.97 [0.72-1.31], p = 0.86. Recurrent MI rates were decreased in the anti-Xa group: OR [95%CI] = 0.86 [0.76-0.98], p = 0.02, number needed to treat (NNT) = 189. The administration of new oral anticoagulants was associated with a strongly increased risk of major bleedings compared with the standard treatment: OR [95%CI] = 3.24 [2.29-4.59], p < 0.001, number needed to harm (NNH) = 104; similarly, intracranial bleeding rates were significantly higher in the anti-Xa arm. CONCLUSIONS: The addition of the new oral anticoagulants on top of standard therapy in the setting of ACS results in an excessive risk of major bleedings without any clear evidence of outweighing clinical benefits.

Drug-coated balloons in treatment of in-stent restenosis: a meta-analysis of randomised controlled trials.

BACKGROUND: Drug-coated balloons (DCBs) have been developed for the percutaneous treatment of coronary artery disease. An initial focus has been the management of in-stent restenosis (ISR) but randomised controlled trials (RCTs) have been small and powered only for angiographic endpoints. OBJECTIVE: The aim of the work was to assess the clinical and angiographic outcomes of patients treated for ISR with DCB versus control (balloon angioplasty or drug-eluting stents) by a meta-analysis of RCTs. METHODS: A comprehensive search was performed of RCTs where patients with ISR were randomly assigned to either DCB or alternative coronary intervention. Outcome measurements were death, myocardial infarction (MI), target lesion revascularisation (TLR), binary definition of restenosis and in-lesion late luminal loss (LLL). RESULTS: Four studies were identified that fulfilled the inclusion criteria. Pooled odds ratios (ORs) were calculated for patients treated for ISR (n = 399). Mean follow-up duration was 14.5 months. DCBs were associated with lower rates of TLR [8.8 vs. 29.7 % OR (95 % confidence interval, CI) 0.20 (0.11-0.36), p < 0.0001], binary restenosis [10.3 vs. 41.3 % OR (95 % CI) 0.13 (0.07-0.24), p < 0.00001] and MI [0.5 vs. 3.8 %, OR (95 % CI) 0.21 (0.04-1.00), p = 0.05]. No significant heterogeneity was identified. CONCLUSION: Drug-coated balloons appear to be effective versus control in reducing TLR and possibly MI versus balloon angioplasty or drug-eluting stents in the management of ISR.

Value of C-reactive protein as a risk factor for acute coronary syndrome: a comparison with apolipoprotein concentrations and lipid profile.

OBJECTIVE: To investigate whether assessment of C-reactive protein (CRP) and apolipoproteins, besides the traditional lipid profile, enhances the assessment process for the risk of acute coronary syndrome (ACS). METHODS: The study group consisted of 220 consecutive patients admitted to hospital within the first 6 hours from the onset of chest pain. Patients were diagnosed with unstable angina (n = 96), non-ST-elevation myocardial infarction (NSTEMI; n = 57), or ST-elevation myocardial infarction (STEMI; n = 67). ACS patients were compared with 116 healthy volunteers in a case-control study. The serum was assayed on admission for CRP, apolipoproteins ApoAI and ApoB100, and lipid parameters. RESULTS: The highest concentrations of CRP were found in NSTEMI and STEMI, with a median value four-fold higher in ACS patients than in controls (P < 0.0001). Only CRP significantly increased the probability of ACS development (adjusted odds ratio for a 1 mg/L increase 1.90; 95% confidence interval [CI] 1.34-2.89) and explained 90% of the variation for ACS development. Similarly, we demonstrated the highest diagnostic accuracy for CRP among all investigated markers (area under the curve 0.80; 95% CI 0.75-0.85). CONCLUSIONS: Our study indicates that CRP superiorly to apolipoproteins and lipid profile facilitates the risk stratification for ACS occurrence.

Clinical efficacy and safety of intracoronary vs. intravenous abciximab administration in STEMI patients undergoing primary percutaneous coronary intervention: a meta-analysis of randomized trials.

Adjunctive therapy with abciximab has been proven to reduce mortality and reinfarction in patients with ST-elevation myocardial infarction (STEMI) referred to invasive management. Standard abciximab regimen consists of an intravenous (IV) bolus followed by a 12-h IV infusion. Experimental studies and small clinical trials suggest the superiority of intracoronary (IC) injection of abciximab over the IV route. We aimed to perform a meta-analysis of randomized controlled trials to assess the clinical efficacy and safety of IC vs. IV abciximab administration in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). The primary endpoint was mortality, while recurrent myocardial infarction and target vessel revascularization (TVR) were selected as secondary endpoints. The safety endpoint was the risk of major bleeding complications. A total of six randomized trials were finally included in the meta-analysis, enrolling a total of 1246 patients. Compared to IV route, IC abciximab was associated with a significant reduction in mortality (odds ratio, OR [95% confidence interval (CI)] =0.43 [0.20-0.94], p=0.03), and TVR (OR [95% CI] =0.53 [0.29-0.99], p=0.05). No differences in terms of recurrent myocardial infarction (OR [95% CI] =0.54 [0.23-1.28], p=0.17) or major bleeding complications (OR [95% CI] =0.91 [0.46-1.79], p=0.79) were observed between the two strategies. The present meta-analysis showed that IC administration of abciximab is associated with significant benefits in mortality at short-term follow-up compared to IV abciximab administration, without any excess of major bleeding in STEMI patients undergoing PPCI. However, further trials are warranted to establish the optimal strategy of abciximab treatment in this setting.

Diagnostic efficacy of myeloperoxidase for the detection of acute coronary syndromes.

BACKGROUND: Early diagnosis of acute coronary syndrome (ACS) is frequently a challenging task, while immediate risk stratification remains crucial for the prompt implementation of appropriate therapy in this setting. Employing markers that increase rapidly after the symptom onset may enhance triage and therapeutic decision-making in patients suspected for ACS. Myeloperoxidase (MPO) exerting proinflammatory and pro-oxidative properties is suggested as a reliable early marker for ACS associated with unfavourable clinical outcome. We assessed the diagnostic efficacy of plasma MPO alone or in combination with cardiac troponin I (cTnI) for detecting ACS in patients presenting with chest pain initiating within 6h before the hospital admission. MATERIAL AND METHODS: A study group consisted of 253 patients diagnosed with ACS and 47 subjects having other heart disease or unspecified chest pain. Clinically healthy volunteers (n=124) served as controls. MPO concentration was measured in plasma (Abbott Diagnostics, USA), while serum was assayed for cTnI, creatine-kinase MB, lipids, glucose, creatinine, brain natriuretic peptide type B and C-reactive protein. RESULTS: Both MPO and cTnI values were significantly lower in non-ACS subjects than in patients with ACS. At 97·5th percentile as cut-off, the superiority of MPO over cTnI was observed in patients with unstable angina and non-ACS subjects. Considerably higher MPO concentrations were demonstrated in the troponin-negative ACS patients on admission who became troponin-positive after 6h. Combined evaluation of MPO and cTnI possessed remarkably higher sensitivity than assessment of cTnI alone in all patients with ACS. CONCLUSIONS: Myeloperoxidase substantially facilitates the early diagnosis of ACS.