Recent advances in the diagnosis and treatment of acute myocardial infarction

The Third Universal Definition of Myocardial Infarction(MI) requires cardiac myocyte necrosis with an increase and/or a decrease in a patient's plasma of cardiac troponin(cT n) with at least one cT n measurement greater than the 99 th percentile of the upper normal reference limit during:(1) symptoms of myocardialischemia;(2) new significant electrocardiogram(ECG) ST-segment/T-wave changes or left bundle branch block;(3) the development of pathological ECG Q waves;(4) new loss of viable myocardium or regional wall motion abnormality identified by an imaging procedure; or(5) identification of intracoronary thrombus by angiography or autopsy.Myocardial infarction,when diagnosed,is now classified into five types.Detection of a rise and a fall of troponin are essential to the diagnosis of acute MI.However,high sensitivity troponin assays can increase the sensitivity but decrease the specificity of MI diagnosis.The ECG remains a cornerstone in the diagnosis of MI and should be frequently repeated,especially if the initial ECG is not diagnostic of MI.There have been significant advances in adjunctive pharmacotherapy,procedural techniques and stent technology in the treatment of patients with MIs.The routine use of antiplatelet agents such as clopidogrel,prasugrel or ticagrelor,in addition to aspirin,reduces patient morbidity and mortality.Percutaneous coronary intervention(PCI) in a timely manner is the primary treatment of patients with acute ST segment elevation MI.Drug eluting coronary stents are safe and beneficial with primary coronary intervention.Treatment with direct thrombin inhibitors during PCI is non-inferior to unfractionated heparin and glycoprotein Ⅱb/Ⅲa receptor antagonists and is associated with a significant reduction in bleeding.The intra-coronary use of a glycoprotein Ⅱb/Ⅲa antagonist can reduce infarct size.Pre- and post-conditioning techniques can provide additional cardioprotection.However,the incidence and mortality due to MI continues to be high despite all these recent advances.The initial ten year experience with autologous human bone marrow mononuclear cells(BMCs) in patients with MI showed modest but significant increases in left ventricular(LV) ejection fraction,decreases in LV endsystolic volume and reductions in MI size.These studies established that the intramyocardial or intracoronary administration of stem cells is safe.However,many of these studies consisted of small numbers of patients who were not randomized to BMCs or placebo.The recent LateT ime,Time,and Swiss Multicenter Trials in patientswith MI did not demonstrate significant improvement in patient LV ejection fraction with BMCs in comparison with placebo.Possible explanations include the early use of PCI in these patients,heterogeneous BMC populations which died prematurely from patients with chronic ischemic disease,red blood cell contamination which decreases BMC renewal,and heparin which decreases BMC migration.In contrast,cardiac stem cells from the right atrial appendage and ventricular septum and apex in the SCIPIO and CADUCEUS Trials appear to reduce patient MI size and increase viable myocardium.Additional clinical studies with cardiac stem cells are in progress.

Feasibility of gastric endoscopic submucosal dissection with continuous low-dose aspirin for patients receiving dual antiplatelet therapy

BACKGROUND Endoscopic submucosal dissection(ESD) for gastric neoplasms during continuous low-dose aspirin(LDA) administration is generally acceptable according to recent guidelines. This retrospective study aimed to investigate the effect of continuous LDA on the postoperative bleeding after gastric ESD in patients receiving dual antiplatelet therapy(DAPT).AIM To investigate the feasibility of gastric ESD with continuous LDA in patients with DAPT.METHODS A total of 597 patients with gastric neoplasms treated with ESD between January2010 and June 2017 were enrolled. The patients were categorized according to type of antiplatelet therapy(APT).RESULTS The postoperative bleeding rate was 6.9%(41/597) in all patients. Patients were divided into the following two groups: no APT(n = 443) and APT(n = 154). APT included single-LDA(n = 95) and DAPT(LDA plus clopidogrel, n = 59)subgroups. In the single-LDA and DAPT subgroups, 56 and 39 patients were received continuous LDA, respectively. The bleeding rate with continuous singleLDA(10.7%) was similar to that with discontinuous single-LDA(10.3%)(P >0.99). Although the bleeding rate with continuous LDA in patients receiving DAPT(23.1%) was higher than that with discontinuous LDA in patients receiving DAPT(5.0%), no significant difference was observed(P = 0.141).CONCLUSION The bleeding rate with continuous LDA in patients receiving DAPT was not statistically different from that with discontinuous LDA in patients receiving DAPT. Therefore, continuous LDA administration may be acceptable for ESD in patients receiving DAPT, although patients should be carefully monitored for possible bleeding.

Synthesis and activity evaluation of some novel derivatives of 4,5,6,7-tetrahydrothieno [3,2-c]-pyridine

Two series of novel derivatives of4,5,6,7-tetrahydrothieno [3,2-c]pyridine were synthesized and structurally characterized by 1^H NMR and MS. Their in vivo antiplatelet aggregation activities were evaluated.

Synthesis, activity evaluation and 3D-QSAR study of some novel derivatives of 4, 5, 6, 7-tetrahydrothieno [3,2-c] pyridine

A series of novel derivatives of 4, 5, 6, 7-tetrahydrothieno [3,2-c] pyridine were synthesized and structurally characterized by 1H NMR and MS. Their in vivo anti-platelet aggregation activities were evaluated. A 3D-QSAR was performed using the CoMFA and the CoMSIA. This model provided useful guidelines for novel anti-platelet thienopyridines design.

Clopidogrel and proton pump inhibitors-where do we stand in 2012?

Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events.Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines.Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19(CYP2C19) and proton pump inhibitors(PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well.Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole,but not for pantoprazole.Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events,when under clopidogrel and PPI treatment at the same time.These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI(especially omeprazole) in the same year.In contrast,more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel.Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality,with high and moderate quality studies not reporting any association,rising concern about unmeasured confounders biasing the low quality studies.Thus,no definite evidence exists for an effect on mortality.Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding,combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.

Modern Antiplatelet Therapy:When Is Clopidogrel the Right Choice?

Platelet inhibition with aspirin is the cornerstone of medical therapy for coronary artery disease.In the era of percutaneous coronary intervention with drug-eluting stents,dual anti-platelet therapy with the addition of clopidogrel(Plavix,Bristol-Myers Squibb,New York,NY)became the mainstay of therapy.However,with the advent of newer oral antiplatelet medications,including prasugrel(Effient?,Eli Lilly,Indianapolis,Indiana)and ticagrelor(Brilinta?,Astra-Zeneca,Cambridge,United Kingdom),choosing the appropriate platelet inhibitor has become more nuanced.The optimal regimen differs based on patient characteristics,clinical situation,and the condition being treated,with differing risk and safety profiles for these medications.This review explores the appropriate use of antiplatelet therapy for stable ischemic heart disease,acute coronary syndrome,stroke,and peripheral vascular disease.Furthermore,we evaluate the data behind the use of antiplatelet therapy in patients on oral anticoagulation.By understanding the biochemistry of platelet aggregation,the pharmacology of platelet inhibitors,and the extensive clinical trial data that informs current guideline recommendations we aim to better understand the role of clopidogrel in patients with cardiovascular disease.

Clopidogrel in ischemic heart disease: A critical appraisal

Aspirin and clopidogrel are the commonest dual antiplatelet agents being used in the secondary prevention of cardiovascular disease. In high risk patients with coronary heart disease, the use of aspirin was associated with a significant risk reduction of myocardial infarction, stroke and vascular death. The use of clopidogrel alone was slightly superior to aspirin, and associated with reduced risk of vascular death, ischemic stroke and myocardial infarction. Dual antiplatelet therapy has been well studied in patients with acute coronary syndrome and those undergoing percutaneous coronary intervention (PCI). In patients with stable coronary heart disease or multiple risk factors the combination of clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing MI, stroke or death from cardiovascular causes.