hirudin and Myocardial-Ischemia

Unprecedented community containment measures were taken following the recent outbreak of COVID-19 in Italy. The aim of the study was to explore the self-reported future compliance of citizens with such measures and its relationship with potentially impactful psychological variables.. An online survey was completed by 931 people (18-76 years) distributed across the Italian territory. In addition to demographics, five dimensions were measured: self-reported compliance with containment measures over time (today, at 7, 14, 30, 60, 90, and 180 days from now) at three hypothetical risk levels (10, 50, 90% of likelihood of contracting the COVID-19), perceived risk, generalized anxiety, intolerance of uncertainty, and relevance of several psychological needs whose satisfaction is currently precluded.. The duration of containment measures plays a crucial role in tackling the spread of the disease as people will be less compliant over time. Psychological needs of citizens impacting on the compliance should be taken into account when planning an easing of the lockdown, along with interventions for protecting vulnerable groups from mental distress.. La apendicitis aguda (AA) es la urgencia quirúrgica abdominal más frecuente. No encontramos estudios específicos que evalúen el impacto de la pandemia causada por el coronavirus 2 (SARS-Cov-2) sobre la AA y su tratamiento quirúrgico. Analizamos la influencia de esta nueva patología sobre la AA.. Estudio observacional retrospectivo en pacientes intervenidos por AA desde enero hasta abril de 2020. Fueron clasificados según el momento de la apendicectomía, antes de la declaración del estado de alarma (Pre-COVID19) y después de la declaración del estado de alarma (Post-COVID19) en España. Se evaluaron variables demográficas, duración de la sintomatología, tipo de apendicitis, tiempo quirúrgico, estancia hospitalaria y complicaciones postoperatorias.. La pandemia por SARS-Cov-2 influye en el momento de diagnóstico de la apendicitis, así como en su grado de evolución y estancia hospitalaria. La peritonitis fue lo más frecuentemente observado. Una sospecha y orientación clínica más temprana, es necesaria para evitar un manejo inadecuado de este trastorno quirúrgico común.. The primary outcome is improvement in PaO. Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).. None.. The gut barrier is crucial in cirrhosis in preventing infection-causing bacteria that normally live in the gut from accessing the liver and other organs via the bloodstream. Herein, we characterised gut inflammation by measuring different markers in stool samples from patients at different stages of cirrhosis and comparing this to healthy people. These markers, when compared with equivalent markers usually measured in blood, were found to be very different in pattern and absolute levels, suggesting that there is significant gut inflammation in cirrhosis related to different immune system pathways to that seen outside of the gut. This provides new insights into gut-specific immune disturbances that predispose to complications of cirrhosis, and emphasises that a better understanding of the gut-liver axis is necessary to develop better targeted therapies.. La surveillance de l’intervalle QT a suscité beaucoup d’intérêt durant la pandémie de la COVID-19 en raison de l’utilisation de médicaments prolongeant l’intervalle QT et les préoccupations quant à la transmission virale par les électrocardiogrammes (ECG) en série. Nous avons posé l’hypothèse que la surveillance en continu de l’intervalle QT par télémétrie était associée à une meilleure détection des épisodes de prolongation de l’intervalle QT.. Nous avons introduit la télémétrie cardiaque en continu (TCC) à l’aide d’un algorithme de surveillance automatisée de l’intervalle QT dans nos unités de COVID-19. Les mesures automatisées quotidiennes de l’intervalle QT corrigé (auto-QTc) en fonction de la fréquence cardiaque maximale ont été enregistrées. Nous avons comparé la proportion des épisodes de prolongation marquée de l’intervalle QTc (QTc long), définie par un intervalle QTc ≥ 500 ms, chez les patients montrant une suspicion de COVID-19 ou ayant la COVID-19 qui avaient été admis avant et après la mise en place de la TCC (groupe témoin. La surveillance en continu de l’intervalle QT est supérieure à la norme de soins dans la détection des épisodes de QTc long et exige peu d’ECG. La réponse clinique aux épisodes de QTc long est sous-optimale.. Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.. Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.. Dust in Egyptian laying hen houses contains high concentrations of microorganisms and endotoxins, which might impair the health of birds and farmers when inhaled. Furthermore, laying hens in Egypt seem to be a reservoir for ESBL-producing Enterobacteriaceae. Thus, farmers are at risk of exposure to ESBL-producing bacteria, and colonized hens might transmit these bacteria into the food chain.. The lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.. Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another. Therefore, further well-designed, larger RCTs are required.. PROSPERO database Identifier: CRD42016041953.. Untouched root canal at cross-section perimeter, the Hero 642 system showed 41.44% ± 5.62% and Reciproc R40 58.67% ± 12.39% without contact with instruments. Regarding the untouched area, Hero 642 system showed 22.78% ± 6.42% and Reciproc R40 34.35% ± 8.52%. Neither instrument achieved complete cross-sectional root canal debridement. Hero 642 system rotary taper 0.02 instruments achieved significant greater wall contact perimeter and area compared to reciprocate the Reciproc R40 taper 0.06 instrument.. Hero 642 achieved higher wall contact perimeter and area but, regardless of instrument size and taper, vital pulp during. The functional properties of the main mechanisms involved in the control of muscle Ca. This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (. Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.. La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea.. In this in vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO. Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.. These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

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Numerous agents are available for anticoagulation during percutaneous coronary intervention (PCI). These agents have been evaluated in a variety of clinical settings, including elective, urgent, and emergent PCI. Although unfractionated heparin remains a frequent choice, accumulating data support the use of newer agents to mitigate bleeding risk, especially in the setting of femoral access and concomitant use of glycoprotein IIb/IIa receptor inhibition. With several antithrombotic agents available, an assessment must be made regarding the ischemic and bleeding risks. This article summarizes existing data examining the benefits and limitations of the various anticoagulants and guidelines for their use.

Topics: Anticoagulants; Fibrinolytic Agents; Heparin; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Treatment Outcome

Bivalirudin is an alternative to unfractionated heparin (UFH) anticoagulation during percutaneous coronary intervention. Previously, we have reported clinical benefit on major bleeding in favor of bivalirudin compared with UFH monotherapy but inconclusive results on mortality. Controversial data have been reported in the last 2 years. We conducted an updated meta-analysis including randomized trials and observational studies, which evaluated ischemic and bleeding outcomes for bivalirudin compared with UFH-only during percutaneous coronary intervention. We included 18 observational studies and 12 randomized trials published from 2003 to 2015. Primary outcomes were major adverse cardiovascular events within 30 days including death, myocardial infarction, and urgent revascularization and stent thrombosis, major bleeding, and transfusion. Overall, we found a significant risk reduction with bivalirudin for major bleeding (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.49 to 0.71, p <0.0001) and for transfusion (OR 0.79, 95% CI 0.66 to 0.95, p = 0.01) and similar risk for major adverse cardiovascular events (OR 0.98, 95% CI 0.86 to 1.12, p = 0.80). However, there was a substantial increased risk of stent thrombosis associated with bivalirudin (OR 1.52, 95% CI 1.11 to 2.08, p = 0.009). No impact on mortality was found. Meta-regression analyses on major bleeding suggested that bivalirudin was more effective than UFH at doses >60 IU/kg and independent of radial access. In conclusion, compared with UFH monotherapy, bivalirudin remains associated with less bleeding risk but higher stent thrombosis risk. Further study remains required to define its role in current antithrombotic armamentarium.

Topics: Antithrombins; Fibrinolytic Agents; Global Health; Heparin; Hirudins; Humans; Incidence; Myocardial Ischemia; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Hemorrhage; Recombinant Proteins; Thrombosis

Bivalirudin significantly reduces 30-day major and minor bleeding compared with unfractionated heparin (UFH), while resulting in similar or lower rates of ischemic events in both patients with stable and unstable coronary disease undergoing percutaneous coronary intervention. We performed a meta-analysis of randomized trials to evaluate the impact of bivalirudin compared with UFH, with or without glycoprotein IIb/IIIa receptor inhibitors (GPI), on the rates of mortality, myocardial infarction (MI), and major bleeding.. We searched electronic databases for randomized controlled trials with >100 patients comparing bivalirudin (±provisional GPI) with UFH with either routine or provisional GPI in patients undergoing percutaneous coronary intervention. The principal efficacy end points were mortality and MI within 30 day, whereas major bleeding was the principal safety end point. We assessed the benefit of bivalirudin for each efficacy end point relative to the baseline bleeding risk, using the control (UFH) major bleeding rate as proxy for that risk.. A total of 12 randomized trials that enrolled 33,261 patients were included. Overall, there was no significant difference in mortality and MI between bivalirudin monotherapy and UFH (±GPI), whereas major bleeding was significantly lower with bivalirudin. Bivalirudin reduced major and minor bleeding across the entire bleeding risk spectrum.. Bivalirudin significantly reduces major and minor bleeding regardless of the estimated baseline hemorrhagic risk.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Regression Analysis; Treatment Outcome

With femoral access, bivalirudin decreases risks of major bleeding after percutaneous coronary intervention (PCI) and provides better net clinical benefit compared to unfractionated heparin (UFH) plus planned glycoprotein IIb/IIIa inhibitors. Whether this benefit exists compared to UFH monotherapy is less clear. We performed a systematic review and meta-analysis to compare outcomes in patients undergoing transfemoral PCI with UFH or bivalirudin. Randomized trials (n = 3) and observational studies (n = 13) comparing bivalirudin to UFH monotherapy were reviewed. Primary outcomes were 30-day rates of major adverse cardiovascular events (MACEs) including death, myocardial infarction (MI), urgent revascularization, as well as all-cause mortality, MI, major bleeding, and blood transfusion. We collected data from 16 studies involving 32,492 patients undergoing PCI. Most observational studies were performed in the United States, whereas all randomized trials were done in Europe. Compared to UFH monotherapy, bivalirudin was associated with similar risk of MACEs (odds ratios [OR] 0.92, 95% confidence interval [CI] 0.75 to 1.12), a substantial 45% relative decrease in major bleeding (OR 0.55, 95% CI 0.43 to 0.72), and a trend in the decrease of transfusion (OR 0.87, 95% CI 0.70 to 1.08). A decrease in mortality was seen in observational studies (OR 0.62, 95% CI 0.45 to 0.85) but remained inconclusive in randomized trials (OR 0.63, 95% CI 0.20 to 2.01). MI rate was similar with the 2 anticoagulants. In conclusion, in patients undergoing transfemoral PCI, the benefit of bivalirudin over UFH monotherapy is driven by a significant decrease in major bleeding with similar rates of MACE. As PCI practice moves toward other bleeding-avoidance strategies such as the radial approach, future studies should focus on the interaction between anticoagulant strategy and access-site choice.

Topics: Angioplasty, Balloon, Coronary; Antithrombins; Cardiovascular Diseases; Heparin; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Postoperative Complications; Postoperative Hemorrhage; Recombinant Proteins; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Clinical Trials as Topic; Coronary Thrombosis; Endothelium, Vascular; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Platelet Activation; Polysaccharides; Postoperative Complications; Recombinant Proteins; Thrombin

The anticoagulant properties of heparin were discovered in 1916, and by the 1930s researchers were evaluating its therapeutic use in clinical trials. Treatment of unstable angina with unfractionated heparin (UFH), in addition to aspirin, was introduced into clinical practice in the early 1980s. UFH was combined with aspirin to suppress thrombin propagation and fibrin formation in patients presenting with acute coronary syndromes (ACS) or patients undergoing percutaneous coronary intervention (PCI). However, UFH stimulates platelets, leading to both activation and aggregation, which may further promote clot formation. Clinical trials have demonstrated that newer agents, such as the low-molecular-weight heparins (LMWHs), are superior to UFH for medical management of unstable angina or non-ST-segment elevation myocardial infarction. Increasingly, the LMWHs have been used as the anticoagulant of choice for patients presenting with ACS. For patients undergoing PCI, LMWH provides no sub-stantial benefit over UFH for anticoagulation; however, direct thrombin inhibitors (DTIs) have demonstrated safety and efficacy in this setting. UFH is likely to be replaced by more effective and safer antithrombin agents, such as DTIs. DTIs have antiplatelet effects, anticoagulant action, and most do not bind to plasma proteins, thereby providing a more consistent dose-response effect than UFH. The FDA has approved 4 parenteral DTIs for various indications: lepirudin, argatroban, bivalirudin, and desirudin. The antiplatelet, anticoagulant, and pharmacokinetic properties of bivalirudin support its use as the anticoagulant of choice for both lower- and higher-risk patients, including those undergoing PCI.

Topics: Acute Disease; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Fondaparinux; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Models, Molecular; Molecular Structure; Myocardial Ischemia; Peptide Fragments; Pipecolic Acids; Platelet Activation; Polysaccharides; Recombinant Proteins; Sulfonamides; Syndrome; Thrombin; Thrombosis

More than 1.2 million percutaneous coronary intervention (PCI) procedures are performed each year in the United States, with average hospital costs of more than $10,000 per procedure. Despite ongoing improvements in device technology and adjunct pharmacology, both ischemic complications (eg, periprocedural myocardial infarction) and bleeding complications remain relatively common and are associated with both increased costs (in the short term) and mortality (in the longer term). Recently, the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 clinical trial demonstrated that the use of the direct thrombin inhibitor, bivalirudin, with provisional glycoprotein (GP) IIb/IIIa inhibitor for selected patients in place of a conventional anticoagulation strategy of heparin and routine use of a GP IIb/IIIa inhibitor, resulted in comparable rates of ischemic complications and a significant reduction in the frequency of both major and minor bleeding complications. A prospectively designed economic analysis was performed using data from 4651 US patients who participated in REPLACE-2. In this analysis, patients who were assigned to the bivalirudin and provisional GP IIb/IIIa inhibitor strategy had anticoagulation costs during PCI that were approximately $400 per patient lower than those with heparin plus routine GP IIb/IIIa inhibition. Bivalirudin also produced corresponding decreases in total in-hospital costs and aggregate 30-day medical care costs. These cost savings derived both from the lower acquisition cost of the antithrombotic therapy and the reduced rate of bleeding complications, which accounted for approximately 20% of the cost offsets. These results suggest that for patients similar to those studied in REPLACE-2 (ie, low to moderate risk PCI procedures), use of bivalirudin and provisional GP IIb/IIIa inhibition compared with heparin and routine GP IIb/IIIa inhibition can result in similar rates of ischemic complications, reduced bleeding, and substantial cost savings to both hospitals and the healthcare system. Whether these benefits can be extended to higher risk patient subsets including patients with non-ST elevation or ST elevation myocardial infarction is currently under investigation.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Cardiac Catheterization; Drug Costs; Hirudins; Humans; Laboratories, Hospital; Myocardial Ischemia; Peptide Fragments; Recombinant Proteins; Thrombosis

Bivalirudin is a member of the direct thrombin inhibitor group of anticoagulants. It has been evaluated as an alternative to unfractionated and low-molecular-weight heparins in the settings of percutaneous coronary intervention (PCI) and acute coronary syndrome (ACS). Results of clinical trials to date suggest bivalirudin is a viable alternative to the use of a heparin combined with a glycoprotein (GP) IIb/IIIa inhibitor in these settings. Thrombin has a central role in coagulation and platelet activation in ACS and during PCI. Its direct inhibition is an attractive target for therapy in these settings. Bivalirudin is a 20 amino acid polypeptide hirudin analog. It displays bivalent and reversible binding to the thrombin molecule, inhibiting its action. Direct inhibition of thrombin with bivalirudin has theoretical pharmacokinetic and pharmacodynamic advantages over the indirect anticoagulants. A reduction in rates of bleeding without loss of anti-thrombotic efficacy has been a consistent finding across multiple clinical trials. There may be economic benefits to the use ofbivalirudin if it permits a lower rate of use of the GP IIb/IIIa inhibitors. This article reviews the pharmacology of bivalirudin and clinical trial evidence to date. There are now data from multiple clinical trials and meta-analyses in the setting of ACS and PCI. Early results from the acute catheterization and urgent intervention strategy (ACUITY) trial are discussed.

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Platelet Aggregation Inhibitors; Recombinant Proteins; Secondary Prevention; Syndrome; Thrombin; Thrombosis

This study evaluates outcomes with bivalirudin vs heparin in various patient subgroups and the overall population during percutaneous coronary interventions (PCI).. Recent data suggest that bivalirudin, a reversible direct thrombin inhibitor, provides ischemic protection superior to heparin and comparable to heparin plus glycoprotein (GP) IIb/IIIa inhibitors but with significantly fewer bleeding complications. Whether this advantage persists in different subgroups has not been fully defined. To our knowledge, this is the largest pooled analysis of bivalirudin to date.. Four randomized controlled trials were identified that compared bivalirudin to heparin (with or without GP IIb/IIIa inhibitors) in PCI. The incidence of death, myocardial infarction (MI), revascularization, and major bleeding at 48 hours was compared between these two agents overall and in patients with and without diabetes mellitus, hypertension, renal insufficiency, and advanced age.. The trials consisted of 11,638 patients (bivalirudin, 5,861; heparin, 5,777). There were no significant differences in patient characteristics between the two groups. At 48 hours, the incidence of death, MI, revascularization, and major bleeding was significantly reduced in the bivalirudin group (7.8% vs 1.08%, P < .001); individual ischemic end points were significantly reduced for death (0.01% vs 0.02%, P = .049) and revascularization (2.0% vs 2.7%, P = .02), with similar reductions for major bleeding (2.7% vs 5.8%, P < .001). Subgroup analysis was generally consistent with the overall findings.. This analysis further supports the superiority of bivalirudin compared with heparin. Bivalirudin provides excellent ischemic protection with a significant reduction of bleeding complications, even in high-risk subgroups.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Heparin; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Postoperative Hemorrhage; Randomized Controlled Trials as Topic; Recombinant Proteins; Time Factors

Unfractionated heparin (UFH) is the most widely used antithrombin during percutaneous coronary intervention (PCI). Despite significant pharmacological and mechanical advancements in PCI, uncertainty remains about the optimal activated clotting time (ACT) for prevention of ischemic or hemorrhagic complications.. We analyzed the outcome of all UFH-treated patients enrolled in 4 large, contemporary PCI trials with independent adjudication of ischemic and bleeding events. Of 9974 eligible patients, maximum ACT was available in 8369 (84%). The median ACT was 297 seconds (interquartile range 256 to 348 seconds). The incidence of death, myocardial infarction, or revascularization at 48 hours, by ACT quartile, was 6.2%, 6.8%, 6.0%, and 5.7%, respectively (P=0.40 for trend). Covariate-adjusted rate of ischemic complications was not correlated with maximal procedural ACT (continuous value, P=0.29). Higher doses of UFH (>5000 U, or up to 90 U/kg) were independently associated with higher rates of events. The incidence of major or minor bleeding at 48 hours, by ACT quartile, was 2.9%, 3.5%, 3.8%, and 4.0%, respectively (P=0.04 for trend). In a multivariable logistic model with a spline transformation for ACT, there was a linear increase in risk of bleeding as the ACT approached 365 seconds (P=0.01), which leveled off beyond that value. Increasing UFH weight-indexed dose was independently associated with higher bleeding rates (OR 1.04 [1.02 to 1.07] for each 10 U/kg, P=0.001).. In patients undergoing PCI with frequent stent and potent platelet inhibition use, ACT does not correlate with ischemic complications and has a modest association with bleeding complications, driven mainly by minor bleeding. Lower values do not appear to compromise efficacy while increasing safety.

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Aspirin; Blood Coagulation Tests; Clopidogrel; Comorbidity; Coronary Restenosis; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Incidence; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Stents; Thrombophilia; Ticlopidine; Tirofiban; Tyrosine

Current treatment strategies for percutaneous coronary revascularization and acute coronary syndromes incorporate thrombin inhibition with either unfractionated or fractionated heparin. The peptide bivalirudin (Hirulog) is a direct thrombin inhibitor whose pharmacological properties differ from those of heparin. We conducted a systematic overview (meta-analysis) to assess the effect of bivalirudin on 4 end points: death, myocardial infarction, major hemorrhage, and the composite of death or infarction.. Six trials (5674 patients) represent the randomized, controlled bivalirudin experience, including 4603 patients undergoing elective percutaneous coronary revascularization and 1071 patients with acute coronary syndromes. ORs for the 4 clinical end points were calculated for each trial. Four trials (4973 patients) that compared bivalirudin with heparin were combined with the use of a random-effects model. In these trials, bivalirudin was associated with a significant reduction in the composite of death or infarction (OR 0.73, 95% CI 0.57 to 0.95; P=0.02) at 30 to 50 days, or 14 fewer events per 1000 patients so treated. There also was a significant reduction in major hemorrhage for the same trials (OR 0.41, 95% CI 0. 32 to 0.52; P<0.001, or 58 fewer events per 1000 patients so treated). A similar analysis combined 2 dose-ranging trials (701 patients) that compared therapeutic (activated partial thromboplastin time more than twice the control time) with subtherapeutic bivalirudin anticoagulation (activated partial thromboplastin time less than twice the control time).. Bivalirudin is at least as effective as heparin, with clearly superior safety. Thus, it provides an unprecedented net clinical benefit over heparin in patients with ischemic heart disease.

Topics: Anticoagulants; Biomarkers; Drug Administration Schedule; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardial Ischemia; Outcome Assessment, Health Care; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins

Unfractionated heparin is commonly used as standard therapy along with aspirin for the management of acute ischaemic syndromes. However, heparin has many limitations including a poor dose effect response and an inability to inactivate clot bound thrombin. Direct thrombin inhibitors inactivate clot bound thrombin and also prevent thrombin induced platelet aggregation. The prototypical direct thrombin inhibitor, hirudin, has been tested in the TIMI 9 and GUSTO II trials. These trials showed a 14% reduction in reinfarction at 30 days, but there was no effect on mortality or on the combined end point of death and nonfatal myocardial infarction (10.8% heparin versus 10.0% hirudin). More moderate bleeding occurred with hirudin than with intravenous heparin. Hirulog has been shown to increase the rate of TIMI grade 3 patency (from 35% to 48%, p = 0.03) at 90 minutes after streptokinase administration, and this is now being tested in a large mortality trial. Further trials are necessary to further test whether patient care can be improved by appropriate doses of these agents administered for an appropriate duration.

Topics: Antithrombins; Clinical Trials as Topic; Dose-Response Relationship, Drug; Hirudins; Humans; Myocardial Ischemia; Syndrome; Thrombolytic Therapy

Topics: Animals; Antithrombins; Hirudins; Humans; Myocardial Ischemia; Thrombin

Most of the clinical evaluation of the direct thrombin inhibitors has been in coronary artery disease. The recent clinical reports suggest that there is a narrower window of safety with recombinant hirudin than initially thought particularly when it is used in conjunction with thrombolytic agents and aspirin in acute myocardial infarction. The efficacy data, however, indicate that the direct thrombin inhibitors have great potential particularly in the initial management of patients with acute unstable angina and non-Q-wave infarction. There is much to learn regarding the mechanism of action, optimal dose, and optimal concomitant therapy in the use of direct thrombin inhibitors in the management of acute coronary ischaemia; and since hirudin and other direct thrombin inhibitors have so much potential in the management of acute coronary ischaemia, it is critical that dose-finding studies be performed to determine safe regimens of these agents to allow their evaluation in large-scale trials with important clinical outcomes. The direct thrombin inhibitors have also shown to have promise in the prevention of deep vein thrombosis in high-risk surgical patients. There is limited clinical data on the other novel anticoagulants which are currently being developed.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Antithrombins; Aspirin; Clinical Trials as Topic; Clinical Trials, Phase II as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Drug Design; Drug Therapy, Combination; Enzyme Activation; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Hirudin Therapy; Hirudins; Humans; Lipoproteins; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Platelet Aggregation Inhibitors; Postoperative Complications; Protein C; Randomized Controlled Trials as Topic; Recombinant Proteins; Thrombolytic Therapy; Thrombophlebitis; Treatment Outcome

Unprecedented community containment measures were taken following the recent outbreak of COVID-19 in Italy. The aim of the study was to explore the self-reported future compliance of citizens with such measures and its relationship with potentially impactful psychological variables.. An online survey was completed by 931 people (18-76 years) distributed across the Italian territory. In addition to demographics, five dimensions were measured: self-reported compliance with containment measures over time (today, at 7, 14, 30, 60, 90, and 180 days from now) at three hypothetical risk levels (10, 50, 90% of likelihood of contracting the COVID-19), perceived risk, generalized anxiety, intolerance of uncertainty, and relevance of several psychological needs whose satisfaction is currently precluded.. The duration of containment measures plays a crucial role in tackling the spread of the disease as people will be less compliant over time. Psychological needs of citizens impacting on the compliance should be taken into account when planning an easing of the lockdown, along with interventions for protecting vulnerable groups from mental distress.. La apendicitis aguda (AA) es la urgencia quirúrgica abdominal más frecuente. No encontramos estudios específicos que evalúen el impacto de la pandemia causada por el coronavirus 2 (SARS-Cov-2) sobre la AA y su tratamiento quirúrgico. Analizamos la influencia de esta nueva patología sobre la AA.. Estudio observacional retrospectivo en pacientes intervenidos por AA desde enero hasta abril de 2020. Fueron clasificados según el momento de la apendicectomía, antes de la declaración del estado de alarma (Pre-COVID19) y después de la declaración del estado de alarma (Post-COVID19) en España. Se evaluaron variables demográficas, duración de la sintomatología, tipo de apendicitis, tiempo quirúrgico, estancia hospitalaria y complicaciones postoperatorias.. La pandemia por SARS-Cov-2 influye en el momento de diagnóstico de la apendicitis, así como en su grado de evolución y estancia hospitalaria. La peritonitis fue lo más frecuentemente observado. Una sospecha y orientación clínica más temprana, es necesaria para evitar un manejo inadecuado de este trastorno quirúrgico común.. The primary outcome is improvement in PaO. Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).. None.. The gut barrier is crucial in cirrhosis in preventing infection-causing bacteria that normally live in the gut from accessing the liver and other organs via the bloodstream. Herein, we characterised gut inflammation by measuring different markers in stool samples from patients at different stages of cirrhosis and comparing this to healthy people. These markers, when compared with equivalent markers usually measured in blood, were found to be very different in pattern and absolute levels, suggesting that there is significant gut inflammation in cirrhosis related to different immune system pathways to that seen outside of the gut. This provides new insights into gut-specific immune disturbances that predispose to complications of cirrhosis, and emphasises that a better understanding of the gut-liver axis is necessary to develop better targeted therapies.. La surveillance de l’intervalle QT a suscité beaucoup d’intérêt durant la pandémie de la COVID-19 en raison de l’utilisation de médicaments prolongeant l’intervalle QT et les préoccupations quant à la transmission virale par les électrocardiogrammes (ECG) en série. Nous avons posé l’hypothèse que la surveillance en continu de l’intervalle QT par télémétrie était associée à une meilleure détection des épisodes de prolongation de l’intervalle QT.. Nous avons introduit la télémétrie cardiaque en continu (TCC) à l’aide d’un algorithme de surveillance automatisée de l’intervalle QT dans nos unités de COVID-19. Les mesures automatisées quotidiennes de l’intervalle QT corrigé (auto-QTc) en fonction de la fréquence cardiaque maximale ont été enregistrées. Nous avons comparé la proportion des épisodes de prolongation marquée de l’intervalle QTc (QTc long), définie par un intervalle QTc ≥ 500 ms, chez les patients montrant une suspicion de COVID-19 ou ayant la COVID-19 qui avaient été admis avant et après la mise en place de la TCC (groupe témoin. La surveillance en continu de l’intervalle QT est supérieure à la norme de soins dans la détection des épisodes de QTc long et exige peu d’ECG. La réponse clinique aux épisodes de QTc long est sous-optimale.. Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.. Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.. Dust in Egyptian laying hen houses contains high concentrations of microorganisms and endotoxins, which might impair the health of birds and farmers when inhaled. Furthermore, laying hens in Egypt seem to be a reservoir for ESBL-producing Enterobacteriaceae. Thus, farmers are at risk of exposure to ESBL-producing bacteria, and colonized hens might transmit these bacteria into the food chain.. The lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.. Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another. Therefore, further well-designed, larger RCTs are required.. PROSPERO database Identifier: CRD42016041953.. Untouched root canal at cross-section perimeter, the Hero 642 system showed 41.44% ± 5.62% and Reciproc R40 58.67% ± 12.39% without contact with instruments. Regarding the untouched area, Hero 642 system showed 22.78% ± 6.42% and Reciproc R40 34.35% ± 8.52%. Neither instrument achieved complete cross-sectional root canal debridement. Hero 642 system rotary taper 0.02 instruments achieved significant greater wall contact perimeter and area compared to reciprocate the Reciproc R40 taper 0.06 instrument.. Hero 642 achieved higher wall contact perimeter and area but, regardless of instrument size and taper, vital pulp during. The functional properties of the main mechanisms involved in the control of muscle Ca. This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (. Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.. La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea.. In this in vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO. Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.. These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

Topics: 3T3-L1 Cells; A Kinase Anchor Proteins; Acetates; Achilles Tendon; Acute Kidney Injury; Acute Pain; Acyclic Monoterpenes; Adenine Nucleotides; Adhesins, Escherichia coli; Adipocytes; Adipocytes, Brown; Adipogenesis; Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adsorption; Adult; Aeromonas hydrophila; Africa; Aged; Aged, 80 and over; Agrobacterium tumefaciens; Air; Air Pollutants; Air Pollution; Air Pollution, Indoor; Algorithms; Alkaloids; Alkynes; Allosteric Regulation; Amines; Amino Acid Sequence; Amino Acids; Amino Acids, Branched-Chain; Aminoisobutyric Acids; Aminopyridines; Amyotrophic Lateral Sclerosis; Anaerobic Threshold; Angiography; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animal Distribution; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Ankle Joint; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Inflammatory Agents; Antibodies, Bacterial; Antifungal Agents; Antimalarials; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Antiretroviral Therapy, Highly Active; Antiviral Agents; Aotidae; Apelin; Apoptosis; Arabidopsis Proteins; Argentina; Arginine; Artemisinins; Arthritis, Experimental; Arthritis, Rheumatoid; Arthroscopy; Aspergillus; Aspergillus niger; Asteraceae; Asthma; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; Auditory Cortex; Autoantibodies; Autophagy; Bacteria; Bacterial Infections; Bacterial Proteins; Bacterial Typing Techniques; Base Composition; Base Sequence; Basketball; Beclin-1; Benzhydryl Compounds; Benzimidazoles; Benzo(a)pyrene; Benzofurans; Benzoxazines; Bereavement; beta Catenin; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Betacoronavirus; Betaine; Binding Sites; Biofilms; Biological Assay; Biological Availability; Biological Evolution; Biomarkers; Biomechanical Phenomena; Biopolymers; Biopsy; Bismuth; Blood Glucose; Blood Platelets; Blood Pressure; Body Composition; Body Weight; Bone Marrow; Bone Marrow Cells; Bone Regeneration; Boron; Botrytis; Brain Ischemia; Brain Neoplasms; Brain-Derived Neurotrophic Factor; Brazil; Breast Neoplasms; Breath Tests; Bronchoalveolar Lavage Fluid; Burkholderia; C-Reactive Protein; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Calcification, Physiologic; Calcium; Calcium Signaling; Calorimetry, Differential Scanning; Cameroon; Camptothecin; Candida; Candida albicans; Capillaries; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Carbohydrate Conformation; Carbon; Carbon Dioxide; Carbon Isotopes; Carcinoma, Ovarian Epithelial; Cardiac Output; Cardiomyopathy, Hypertrophic; Cardiotonic Agents; Cardiovascular Diseases; Caregivers; Carps; Case-Control Studies; Catalase; Catalysis; Cats; CD4 Lymphocyte Count; Cell Culture Techniques; Cell Differentiation; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Cellulose; Centrosome; Ceratopogonidae; Chickens; Child; China; Cholera Toxin; Choline; Cholinesterases; Chromatography, High Pressure Liquid; Chromatography, Liquid; Chromatography, Micellar Electrokinetic Capillary; Chromatography, Reverse-Phase; Chronic Disease; Cinnamates; Cities; Citrates; Climate Change; Clinical Trials, Phase III as Topic; Coal; Coal Mining; Cohort Studies; Coinfection; Colchicine; Colony Count, Microbial; Colorectal Neoplasms; Coloring Agents; Common Cold; Complement Factor H; Computational Biology; Computer Simulation; Continuous Positive Airway Pressure; Contrast Media; Coordination Complexes; Coronary Artery Bypass; Coronavirus 3C Proteases; Coronavirus Infections; Coronavirus Protease Inhibitors; Corynebacterium glutamicum; Cosmetics; COVID-19; Creatinine; Cross-Sectional Studies; Crotonates; Crystallography, X-Ray; Cues; Culicidae; Culture Media; Curcuma; Cyclopentanes; Cyclopropanes; Cymbopogon; Cystine; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; Cytokines; Databases, Genetic; Death; Dendritic Cells; Density Functional Theory; Depsides; Diabetes Mellitus, Type 2; Diamond; Diarylheptanoids; Dibenzofurans; Dibenzofurans, Polychlorinated; Diclofenac; Diet; Dietary Carbohydrates; Dietary Supplements; Diffusion Magnetic Resonance Imaging; Dioxins; Diphenylamine; Disease Outbreaks; Disease Susceptibility; Disulfides; Dithiothreitol; Dizocilpine Maleate; DNA Methylation; DNA-Binding Proteins; DNA, Bacterial; Dogs; Dose-Response Relationship, Drug; Double-Blind Method; Doublecortin Protein; Drosophila melanogaster; Droughts; Drug Carriers; Drug Combinations; Drug Delivery Systems; Drug Liberation; Drug Resistance; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Dust; Dynactin Complex; Dysferlin; Echo-Planar Imaging; Echocardiography; Edaravone; Egypt; Elasticity; Electrodes; Electrolytes; Emodin; Emtricitabine; Endometriosis; Endothelium, Vascular; Endotoxins; Energy Metabolism; Energy Transfer; 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Genitalia; Genotype; Glomerulonephritis, IGA; Glottis; Glucocorticoids; Glucose; Glucuronides; Glutathione Transferase; Glycogen Synthase Kinase 3 beta; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Grassland; Guinea Pigs; Half-Life; Head Kidney; Heart Atria; Heart Rate; Heart Septum; HEK293 Cells; Hematopoietic Stem Cells; Hemodynamics; Hep G2 Cells; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Hepatocytes; Hesperidin; High-Frequency Ventilation; High-Temperature Requirement A Serine Peptidase 1; Hippocampus; Hirudins; History, 20th Century; History, 21st Century; HIV Infections; Homeostasis; Hominidae; Housing, Animal; Humans; Hydrocarbons, Brominated; Hydrogen Bonding; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydroxybutyrates; Hydroxyl Radical; Hypertension; Hypothyroidism; Image Interpretation, Computer-Assisted; Immunoconjugates; Immunogenic Cell Death; Indoles; Infant, Newborn; Infant, Premature; Infarction, Middle Cerebral Artery; Inflammation; 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To compare bleeding and clinical events of patients with stable angina or silent ischemia undergoing percutaneous coronary intervention (PCI) treated with unfractionated heparin (UFH) or bivalirudin.. Few direct comparisons between UFH monotherapy versus bivalirudin exist for patients with stable ischemic heart disease undergoing PCI.. A prospective, investigator-initiated, single-center, single-blinded, randomized trial of UFH versus bivalirudin was conducted. The primary endpoint was all bleeding (major and minor) from index-hospitalization to 30 days post discharge. Secondary endpoints included major adverse cerebral and cardiovascular events (MACCE) and net adverse clinical events (NACE).. Two-hundred-sixty patients were randomized for treatment with either UFH (n = 123) (47%) or bivalirudin (n = 137) (53%) There were no significant differences in baseline clinical and angiographic characteristics between the two groups. Primary endpoint was similar in both groups (10.9% with bivalirudin vs 7.3% with UFH [P = 0.31]). Major bleeding rates were 5.8% and 2.4%, respectively (P = 0.17). There was a higher MACCE (3.5% vs 0%, P = 0.03) and NACE (8.8% vs 2.4%, P = 0.03) rate with bivalirudin compared to UFH, respectively. Bivalirudin had increased odds of NACE (OR = 3.65, 95% CI: 1.00-13.3.6). Death and stent thrombosis rates were low and similar in both groups. Radial access was associated with fewer bleeding events compared to femoral access but not statistically significant (P = 0.29).. Among patients with stable angina or silent ischemia, there was no difference between UFH and bivalirudin in bleeding rates up to 30-days post-PCI. MACCE and NACE were higher among the bivalirudin group. Radial access was associated with a numerically lower rate of bleeding compared with femoral access.

Topics: Aged; Anticoagulants; Coronary Artery Disease; Drug Monitoring; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Recombinant Proteins; Thrombosis; Treatment Outcome

The purpose of this study was to evaluate the impact of arterial access site on bleeding and ischaemic outcomes, overall and by treatment strategy, in patients with acute coronary syndromes (ACS).. In the ACUITY trial, 13,819 patients with moderate and high-risk ACS were randomised to either heparin (unfractionated or enoxaparin) plus a glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin plus a GPI, or bivalirudin alone. Per operator choice, femoral access was utilised in 11,989 patients (93.8%) and radial access in 798 patients (6.2%). There was no significant difference in composite ischaemia between the radial and femoral approaches at 30 days (8.1% vs 7.5%, p=0.18) or 1 year (14.7% vs 15.5%, p=0.77), although fewer major bleeding complications occurred with the use of radial access (3.0%vs4.8%, p=0.03). Use of bivalirudin monotherapy was associated with significantly less 30-day major bleeding than heparin plus GPI after femoral access (3.0% vs 5.8%, p<0.0001), but not with radial access (4.2% vs 2.2%, P=0.19). Major or minor organ bleeding was reduced with bivalirudin monotherapy compared to heparin plus GPI to a similar extent with both femoral (4.1% vs 7.4%, P<0.0001) and radial (4.9% vs 7.2%, P=0.26) access.. Transradial compared to femoral arterial access is associated with similar rates of composite ischaemia and with fewer major bleeding complications in patients with ACS managed invasively. Bivalirudin monotherapy compared to heparin plus GPIs significantly reduces access site related major bleeding complications with femoral but not radial artery access, though non-access site related bleeding is reduced by bivalirudin monotherapy in all patients.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Blood Transfusion; Catheterization, Peripheral; Drug Therapy, Combination; Enoxaparin; Female; Femoral Artery; Hemorrhage; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Proportional Hazards Models; Punctures; Radial Artery; Recombinant Proteins; Risk Assessment; Time Factors; Treatment Outcome; Young Adult

In this substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial, we investigated the relationship between chronic kidney disease (CKD) and clinical outcomes, and compared the safety and efficacy of bivalirudin monotherapy versus heparin plus a glycoprotein IIb/IIIa inhibitor (GPI).. CKD is an important predictor of prognosis in the general population. The outcomes of patients with CKD and acute coronary syndromes (ACS) have not been well studied.. In the ACUITY study, 13,819 patients with moderate- and high-risk ACS undergoing an early, invasive strategy were randomly assigned to 1 of 3 antithrombin regimens: a heparin plus a GPI, bivalirudin plus a GPI, or bivalirudin monotherapy. CKD (creatinine clearance <60 ml/min) was present in 2,469 (19.1%) of 12,939 randomized patients with baseline creatinine clearance data.. Patients with CKD had worse 30-day and 1-year clinical outcomes than those with normal renal function. There were no significant differences between bivalirudin monotherapy and heparin plus a GPI in rates of 30-day composite ischemia (11.1% vs. 9.4%, p = 0.27) and net clinical adverse outcomes (16.1% vs. 16.9%, p = 0.65). There was remarkably less major bleeding (6.2% vs. 9.8%, p = 0.008) at 30 days, but no significant difference in 1-year composite ischemia (22.0% vs. 18.9%, p = 0.10) or mortality (7.1% vs. 7.3%, p = 0.96).. In patients with ACS, CKD is associated with higher 30-day and 1-year adverse event rates. Compared with heparin plus a GPI, the use of bivalirudin monotherapy in patients with CKD results in nonstatistically different ischemic outcomes, but significantly less 30-day major bleeding.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Biomarkers; Chronic Disease; Coronary Artery Bypass; Creatinine; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Kidney Diseases; Logistic Models; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Odds Ratio; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Recombinant Proteins; Risk Assessment; Time Factors; Treatment Outcome; Triage

The aim of this study was to compare outcomes in patients receiving consistent unfractionated heparin (UFH)/enoxaparin (ENOX) therapy and in those switched at randomization to bivalirudin monotherapy.. Crossover between UFH and ENOX has been associated with increased adverse outcomes in patients with acute coronary syndromes. The ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial demonstrated superior net clinical outcomes with similar rates of ischemia and significantly less major bleeding with bivalirudin monotherapy compared with UFH/ENOX plus a glycoprotein (GP) IIb/IIIa inhibitor. It is unknown if these results would be preserved in patients switched from UFH/ENOX to bivalirudin monotherapy.. We compared composite ischemia, major bleeding, and net clinical outcomes at 30 days in patients receiving consistent UFH/ENOX therapy and in those switched at randomization from pre-treatment with UFH/ENOX to bivalirudin monotherapy. We also compared outcomes in patients naive to antithrombin therapy who were randomized to UFH/ENOX or bivalirudin monotherapy.. Two thousand one hundred thirty-seven patients received consistent UFH/ENOX (UFH n = 1,294, ENOX n = 843), and 2,078 patients pre-treated with UFH/ENOX were switched to bivalirudin. Patients switching to bivalirudin had similar rates of ischemia (6.9% vs. 7.4%, p = 0.52), less major bleeding (2.8% vs. 5.8%, p < 0.01), and improved net clinical outcomes (9.2% vs. 11.9%, p < 0.01) than those on consistent UFH/ENOX plus a GP IIb/IIIa inhibitor. Patients naive to antithrombin therapy who were administered bivalirudin (n = 1,427) had similar rates of ischemia (6.2% vs. 5.5%, p = 0.47), less major bleeding (2.5% vs. 4.9%, p < 0.001), and similar net clinical outcomes (8.0% vs. 9.4%, p = 0.17) compared with naive patients administered UFH/ENOX plus a GP IIb/IIIa inhibitor (n = 1,462).. Switching from UFH/ENOX to bivalirudin monotherapy results in comparable ischemic outcomes and an approximately 50% reduction in major bleeding compared with consistent UFH/ENOX plus a GP IIb/IIIa inhibitor. Patients naive to antithrombin therapy administered bivalirudin monotherapy had a significant reduction in bleeding and similar rates of ischemia compared with naive patients initiated with UFH or ENOX plus a GP IIb/IIIa inhibitor.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Anticoagulants; Enoxaparin; Female; Heart Conduction System; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Factors; Treatment Outcome

The aim of this study was to assess anticoagulation with the direct thrombin inhibitor bivalirudin during percutaneous coronary intervention in individuals with moderate and high-risk acute coronary syndromes.. 13,819 individuals in the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial were prospectively randomly assigned to receive heparin (unfractionated or enoxaparin) plus glycoprotein IIb/IIIa inhibitors, bivalirudin plus glycoprotein IIb/IIIa inhibitors, or bivalirudin alone. Of these individuals, 7789 underwent percutaneous coronary intervention after angiography. The effect of the three regimens on the primary 30-day endpoints of composite ischaemia (death, myocardial infarction, or unplanned revascularisation for ischaemia), major bleeding, and net clinical outcomes (composite ischaemia or major bleeding) was assessed in this subgroup. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, with the number NCT00093158.. Of the individuals who underwent percutaneous coronary intervention, 2561 received heparin plus glycoprotein IIb/IIIa inhibitors, 2609 received bivalirudin plus glycoprotein IIb/IIIa inhibitors, and 2619 received bivalirudin alone. 26 (0.3%) individuals dropped out or were lost to follow-up. There was no significant difference in the proportion of individuals with composite ischaemia, major bleeding, or net clinical outcomes at 30 days between those who received bivalirudin plus glycoprotein IIb/IIIa inhibitors and those who received heparin plus glycoprotein IIb/IIIa inhibitors (composite ischaemia: 243 [9%] patients vs 210 [8%] patients, p=0.16; major bleeding: 196 [8%] patients vs 174 [7%] patients, p=0.32; net clinical outcomes: 389 [15%] patients vs 341 [13%] patients, p=0.1). Rates of composite ischaemia were much the same in those who received bivalirudin alone and those who received heparin plus glycoprotein IIb/IIIa inhibitors (230 [9%] patients vs 210 [8%] patients, p=0.45); however, there were significantly fewer individuals who experienced major bleeding among those who received bivalirudin alone than among those who received heparin plus glycoprotein IIb/IIIa inhibitors (92 [4%] patients vs 174 [7%] patients, p<0.0001, relative risk 0.52, 95% CI 0.40-0.66), resulting in a trend towards better 30-day net clinical outcomes (303 [12%] patients vs 341 [13%] patients, p=0.057; 0.87, 0.75-1.00).. Substitution of unfractionated heparin or enoxaparin with bivalirudin results in comparable clinical outcomes in patients with moderate and high-risk acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors in whom percutaneous coronary intervention is done. Anticoagulation with bivalirudin alone suppresses adverse ischaemic events to a similar extent as does heparin plus glycoprotein IIb/IIIa inhibitors, while significantly lowering the risk of major haemorrhagic complications.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Combined Modality Therapy; Drug Therapy, Combination; Enoxaparin; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Recombinant Proteins; Treatment Outcome

Adverse events occur following non-ST elevation acute coronary syndromes (NSTE ACS). However, the timing of these events in relation to index event is less clear.. Accordingly, we evaluated 26,466 NSTE ACS patients from the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb), Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), and Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON) A and B trials to ascertain the timing of adverse events. Outcomes of interest were death, myocardial infarction (MI), and death or MI at 180 days. Logistic regression modeling for death was used to categorize patients into low-, medium-, and high-risk groups.. At 6 months, 6.2% of patients died, 12.1% had MI, and 15.7% suffered death or MI. From 15% to 40% of these events occurred beyond 30 days. At 6 months, 3%, 4%, and 13% of patients died in low-, medium-, and high-risk groups, respectively. However, the proportion of patients dying beyond 30 days was similar in the three groups (44%, 43%, and 41% of death, respectively). Similarly, whereas death or MI increased with higher risk (11%, 14%, and 23%, respectively), the proportion of patients with this event beyond 30 days did not differ in the three strata (22%, 20%, and 25%, respectively).. Our study provides important insights into the timing of adverse events and suggests that the substantial proportion of patients suffer subsequent adverse events after their index NSTE ACS. Thus, these data call for continuous surveillance for these events and efforts beyond the acute phase at increasing adherence to evidence-based therapies to improve the outcomes of these patients.

Topics: Acute Disease; Aged; Angina, Unstable; Aspirin; Female; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Risk Assessment; Risk Factors; Survival; Time Factors

At 30-day follow-up, patients with moderate- and high-risk acute coronary syndromes (ACS) undergoing early invasive treatment in the ACUITY trial with bivalirudin monotherapy vs heparin plus glycoprotein (GP) IIb/IIIa inhibitors had noninferior rates of adverse ischemic events with reduced rates of major bleeding. Deferred upstream use of GP IIb/IIIa inhibitors for selective administration to patients undergoing percutaneous coronary intervention (PCI) resulted in a significant reduction in major bleeding, although a small increase in composite ischemia could not be excluded.. To determine 1-year ischemic outcomes for patients in the ACUITY trial.. A prospective, randomized, open-label trial with 1-year clinical follow-up at 450 academic and community-based institutions in 17 countries. A total of 13,819 patients with moderate- and high-risk ACS undergoing invasive treatment were enrolled between August 23, 2003, and December 5, 2005.. Patients were assigned to heparin plus GP IIb/IIIa inhibitors (n = 4603), bivalirudin plus GP IIb/IIIa inhibitors (n = 4604), or bivalirudin monotherapy (n = 4612). Of these patients, 4605 were assigned to routine upstream GP IIb/IIIa administration and 4602 were deferred to selective GP IIb/IIIa inhibitor administration.. Composite ischemia (death, myocardial infarction, or unplanned revascularization for ischemia) at 1 year.. Composite ischemia at 1 year occurred in 15.4% of patients assigned to heparin plus GP IIb/IIIa inhibitors and 16.0% assigned to bivalirudin plus GP IIb/IIIa inhibitors (compared with heparin plus GP IIb/IIIa inhibitors, HR, 1.05; 95% CI, 0.95-1.16; P = .35), and 16.2% assigned to bivalirudin monotherapy (HR, 1.06; 95% CI, 0.95-1.17; P = .29). Mortality at 1 year occurred in an estimated 3.9% of patients assigned to heparin plus GP IIb/IIIa inhibitors, 3.9% assigned to bivalirudin plus GP IIb/IIIa inhibitors (HR, 0.99; 95% CI, 0.80-1.22; P = .92), and 3.8% assigned to bivalirudin monotherapy (HR, 0.96; 95% CI, 0.77-1.18; P = .67). Composite ischemia occurred in 16.3% of patients assigned to deferred use compared with 15.2% of patients assigned to upstream administration (HR, 1.08; 95% CI, 0.97-1.20; P = .15).. At 1 year, no statistically significant difference in rates of composite ischemia or mortality among patients with moderate- and high-risk ACS undergoing invasive treatment with the 3 therapies was found. There was no statistically significant difference in the rates of composite ischemia between patients receiving routine upstream administration of GP IIb/IIIa inhibitors vs deferring their use for patients undergoing PCI.. clinicaltrials.gov Identifier: NCT00093158.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Drug Therapy, Combination; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Treatment Outcome

The goal of this study was to evaluate glycoprotein IIb/IIIa inhibition with eptifibatide when administered with indirect thrombin inhibition as compared with monotherapy with direct thrombin inhibition with bivalirudin among patients with non-ST-segment elevation acute coronary syndromes (ACS).. The optimal combination of antiplatelet and antithrombin regimens that maximizes efficacy and minimizes bleeding among patients with non-ST-segment elevation ACS undergoing percutaneous coronary intervention (PCI) is unclear.. A total of 857 patients with non-ST-segment elevation ACS were assigned randomly to eptifibatide + reduced dose unfractionated heparin (n = 298), eptifibatide + reduced-dose enoxaparin (n = 275), or bivalirudin monotherapy (n = 284).. Among angiographically evaluable patients (n = 754), the primary end point of post-PCI coronary flow reserve was significantly greater with bivalirudin (1.43 vs. 1.33 for pooled eptifibatide arms, p = 0.036). Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade more often was normal with eptifibatide treatment compared with bivalirudin (57.9% vs. 50.9%, p = 0.048). The duration of ischemia on continuous Holter monitoring after PCI was significantly longer among patients treated with bivalirudin (169 vs. 36 min, p = 0.013). There was no excess of TIMI major bleeding among patients treated with eptifibatide compared with bivalirudin (0.7%, n = 4 vs. 0%, p = NS), but TIMI minor bleeding was increased (2.5% vs. 0.4%, p = 0.027) as was transfusion (4.4% to 0.4%, p < 0.001).. Among moderate- to high-risk patients with ACS undergoing PCI, coronary flow reserve was greater with bivalirudin than eptifibatide. Eptifibatide improved myocardial perfusion and reduced the duration of post-PCI ischemia but was associated with higher minor bleeding and transfusion rates. Ischemic events and biomarkers for myonecrosis, inflammation, and thrombin generation did not differ between agents.

Topics: Acute Disease; Angina, Unstable; Angioplasty, Balloon, Coronary; Antithrombins; Drug Therapy, Combination; Enoxaparin; Eptifibatide; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Inflammation; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Peptides; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Postoperative Hemorrhage; Recombinant Proteins; Syndrome

Current guidelines for patients with moderate- or high-risk acute coronary syndromes recommend an early invasive approach with concomitant antithrombotic therapy, including aspirin, clopidogrel, unfractionated or low-molecular-weight heparin, and glycoprotein IIb/IIIa inhibitors. We evaluated the role of thrombin-specific anticoagulation with bivalirudin in such patients.. We assigned 13,819 patients with acute coronary syndromes to one of three antithrombotic regimens: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. The primary end points were a composite ischemia end point (death, myocardial infarction, or unplanned revascularization for ischemia), major bleeding, and the net clinical outcome, defined as the combination of composite ischemia or major bleeding.. Bivalirudin plus a glycoprotein IIb/IIIa inhibitor, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with noninferior 30-day rates of the composite ischemia end point (7.7% and 7.3%, respectively), major bleeding (5.3% and 5.7%), and the net clinical outcome end point (11.8% and 11.7%). Bivalirudin alone, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with a noninferior rate of the composite ischemia end point (7.8% and 7.3%, respectively; P=0.32; relative risk, 1.08; 95% confidence interval [CI], 0.93 to 1.24) and significantly reduced rates of major bleeding (3.0% vs. 5.7%; P<0.001; relative risk, 0.53; 95% CI, 0.43 to 0.65) and the net clinical outcome end point (10.1% vs. 11.7%; P=0.02; relative risk, 0.86; 95% CI, 0.77 to 0.97).. In patients with moderate- or high-risk acute coronary syndromes who were undergoing invasive treatment with glycoprotein IIb/IIIa inhibitors, bivalirudin was associated with rates of ischemia and bleeding that were similar to those with heparin. Bivalirudin alone was associated with similar rates of ischemia and significantly lower rates of bleeding. (ClinicalTrials.gov number, NCT00093158 [ClinicalTrials.gov].).

Topics: Adult; Aged; Aged, 80 and over; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Bypass; Drug Therapy, Combination; Enoxaparin; Female; Hemorrhage; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins

The present study assessed the magnitude of inhibition of platelet aggregation induced by adenosine diphosphate and thrombin receptor activating peptide achieved with unfractionated heparin, the direct thrombin inhibitor bivalirudin, and the glycoprotein IIb/IIIa inhibitor eptifibatide in patients who underwent percutaneous coronary intervention and and were treated with concomitant aspirin and clopidogrel.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Clopidogrel; Drug Therapy, Combination; Eptifibatide; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Peptides; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Preoperative Care; Recombinant Proteins; Ticlopidine; Treatment Outcome

The purpose of this study was to determine how risks associated with increasing age differed in patients treated with percutaneous transluminal coronary angioplasty versus thrombolysis.. Advancing age is a risk factor for adverse outcome in patients with acute myocardial infarction. Primary angioplasty has been thought to be particularly beneficial in higher risk patients including the elderly. There is, however, limited data on any differential incremental benefit of angioplasty compared with thrombolysis in candidates for either treatment.. In the GUSTO-IIb angioplasty substudy, 1,138 patients were randomized to receive primary angioplasty or accelerated tissue-type plasminogen activator (t-PA). The effect of age on outcome was assessed as a discrete and continuous variable for each treatment group. Models using age as a linear factor as well as cubic spline transformations were used for the major end points of 30-day death or disabling stroke; death or reinfarction; and death, reinfarction or disabling stroke.. For each 10-year patient group, outcome was improved with angioplasty (n = 565) compared with t-PA (n = 573). Irrespective of treatment, however, risk increased with age. After adjusting for baseline characteristics, each increment of 10 years of age increased the risk of death or myocardial infarction by 1.32 (95% confidence interval 1.04 to 1.76, p = 0.022). For all adverse outcomes, this incremental effect of increasing age was constant.. Advancing age is associated with worse outcomes, and the risks increase in proportion to age. Although primary angioplasty improves outcomes over thrombolysis, it does not appear to be more beneficial in older than in younger patient groups. The incremental adverse effect of age does not vary by treatment strategy.

Topics: Adult; Aged; Aged, 80 and over; Aging; Angioplasty, Balloon, Coronary; Coronary Angiography; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin; Hirudin Therapy; Hirudins; Humans; Injections, Intravenous; Male; Middle Aged; Myocardial Ischemia; Recurrence; Survival Rate; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome

The objectives of the Organization to Assess Strategies for Ischemic Syndromes (OASIS) Pilot Study (phase 2) were (1) to compare the efficacy, safety, and feasibility of recombinant hirudin versus unfractionated heparin as short-term therapy in patients with acute coronary syndromes without ST elevation and (2) to compare the efficacy and safety of long-term therapy with warfarin and aspirin versus standard therapy with aspirin alone in the same patient population. Investigators at 31 Canadian centers randomized 909 patients to receive either medium-dose hirudin, low-dose hirudin, or unfractionated heparin. The incidence of the 7-day primary composite outcome of cardiovascular death, new myocardial infarction (MI), or refractory angina was significantly lower among patients who received hirudin than among those assigned to unfractionated heparin. A subset of these patients was subsequently randomized to long-term, low-intensity (international normalized ratio [INR] < 1.5) or moderate-intensity (INR 2-2.5) anticoagulant treatment with warfarin or to standard therapy. In this substudy, promising results were observed in favor of moderate-intensity warfarin. These findings provided the rationale for the design and conduct of the large-scale, phase III OASIS-2 trial.

Topics: Acute Disease; Aged; Angina, Unstable; Anticoagulants; Aspirin; Canada; Death, Sudden, Cardiac; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Electrocardiography; Feasibility Studies; Female; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Pilot Projects; Recombinant Proteins; Recurrence; Registries; Treatment Outcome; Warfarin

Patients with acute ischemic syndromes (AIS) suffer high rates of recurrent ischemic events despite aspirin treatment. Long-term therapy with oral anticoagulants in addition to aspirin may reduce this risk. We studied the effects of long-term warfarin at 2 intensities in patients with AIS without ST elevation in 2 consecutive randomized controlled studies.. In phase 1, after the cessation of 3 days of intravenous antithrombotic therapy, 309 patients were randomized to receive fixed low-dose (3 mg/d) warfarin for 6 months that produced a mean international normalized ratio (INR) of 1.5+/-0.6 or to standard therapy. Eighty-seven percent of patients received aspirin in both groups. The rates of cardiovascular (CV) death, new myocardial infarction (MI), and refractory angina at 6 months were 6.5% in the warfarin group and 3.9% in the standard therapy group (relative risk [RR], 1. 66; 95% CI, 0.62 to 4.44; P=0.31). The rates of death, new MI, and stroke were 6.5% in the warfarin group and 2.6% in the standard therapy group (RR, 2.48; 95% CI, 0.80 to 7.75; P=0.10). The overall rate of rehospitalization for unstable angina was 21% and did not differ significantly between the groups. Four patients in the warfarin group (2.6%) and none in the control group experienced a major bleed (RR, 2.48; 95% CI, 0.80 to 7.75), and there was a significant excess of minor bleeds in the warfarin group (14.2% versus 2.6%; RR, 5.46; 95% CI, 1.93 to 15.5; P=0.001). In phase 2, the protocol was modified, and 197 patients were randomized <48 hours from the onset of symptoms to receive warfarin at an adjusted dose that produced a mean INR of 2.3+/-0.6 or standard therapy for 3 months. Eighty-five percent received aspirin in both groups. The rates of CV death, new MI, and refractory angina at 3 months were 5. 1% in the warfarin group and 12.1% in the standard group (RR, 0.42; 95% CI, 0.15 to 1.15; P=0.08). The rates of all death, new MI, and stroke were 5.1% in the warfarin group and 13.1% in the standard therapy group (RR, 0.39; 95% CI, 0.14 to 1.05; P=0.05). Significantly fewer patients were rehospitalized for unstable angina in the warfarin group than in the control group (7.1% and 17.2%, respectively; RR, 0.42; 95% CI, 0.18 to 0.96; P=0.03). Two patients in the warfarin group and 1 in the control group experienced a major bleed, and there was a significant excess of minor bleeds in the warfarin group (28.6% versus 12.1%; RR, 2.36; 95% CI, 1.37 to 4.36; P=0.004).. Long-term treatment with moderate-intensity warfarin (INR, 2.0 to 2.5) plus aspirin but not low-intensity warfarin (INR, 1.5) plus aspirin appears to reduce the rate of recurrent ischemic events in patients with AIS without ST elevation.

Topics: Administration, Oral; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Aspirin; Coronary Artery Bypass; Electrocardiography; Hemorrhage; Hirudins; Humans; Infusions, Intravenous; Myocardial Infarction; Myocardial Ischemia; Patient Compliance; Pilot Projects; Platelet Aggregation Inhibitors; Warfarin

Despite the use of aspirin and heparin, patients with acute ischemic syndromes are at risk of myocardial infarction (MI) or refractory ischemia. Therefore, evaluation of more potent antithrombotic therapies is warranted.. Patients (n=909) with unstable angina or suspected acute MI without ST-segment elevation were randomized to receive heparin (5000 IU bolus+1000 to 1200 U/h, n=371), low-dose hirudin (LDHir) (0.2 mg/kg bolus+0.10 mg x kg(-1) x h(-1) infusion, n=271), or medium-dose hirudin (MDHir) (0.4 mg/kg bolus+0.15 mg x kg(-1) x h(-1) infusion, n=267) for 72 hours. At 7 days, 6.5% of patients in the heparin group, 4.4% in the LDHir group, and 3.0% in the MDHir group (P=.267 heparin versus low-dose hirudin; P=.047 heparin versus medium-dose hirudin) suffered cardiovascular death, new MI, or refractory angina (primary outcome). The proportions with cardiovascular death, new MI, or refractory or severe angina (secondary outcome) were 15.6%, 12.5%, and 9.4%, respectively (P=.27 for heparin versus LDHir; P=.02 for heparin versus MDHir). The rates of new MI were 4.9%, 2.6%, and 1.9%, respectively (P=.14 heparin versus LDHir; P=.046 heparin versus MDHir). Fewer patients underwent coronary artery bypass graft surgery in the two hirudin groups (3.7% low-dose, 1.1% medium-dose group) compared with heparin (4.0%) (P=.028 for heparin versus MDHir). After cessation of study treatments, there was an increase in ischemic events in the LDHir group at approximately 24 hours and at approximately 5 days in the medium-dose group. Nevertheless, at 180 days, the differences between hirudin and heparin persisted.. Hirudin, especially at the medium dose, appears to be superior to heparin in preventing ischemic outcomes in unstable angina or acute MI without ST elevation.

Topics: Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Electrocardiography; Female; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Revascularization; Partial Thromboplastin Time; Pilot Projects; Recombinant Proteins

We investigated whether bivalirudin is more effective than heparin in preventing ischemic complications in high risk patients undergoing coronary angioplasty for thrombus-containing lesions detected by angiography.. Heparin is administered during coronary angioplasty to prevent closure of the dilated vessel. Bivalirudin (Hirulog) is a direct thrombin inhibitor that can be safely substituted for heparin during angioplasty. Bivalirudin has several theoretic advantages over heparin as an anticoagulant agent.. We performed an observational analysis of the Hirulog Angioplasty Study in which 4,098 patients with unstable or postinfarction angina were randomized to receive either bivalirudin or heparin during coronary angioplasty. The study group for this analysis consisted of 567 patients who had thrombus-containing lesions on angiography. The primary end point was death, myocardial infarction, emergency coronary artery bypass graft surgery or abrupt vessel closure before hospital discharge.. Patients with thrombus-containing lesions had a higher incidence of myocardial infarction (5.1% vs. 3.2%, p = 0.03) and abrupt vessel closure (13.6% vs. 8.3%, p < 0.001) than those without thrombus. In patients with thrombus-containing lesions, however, the incidence of the primary end point was not different between the bivalirudin and heparin treatment groups. Furthermore, no difference in the incidence of ischemic events at 6 months was seen between the treatment groups.. Bivalirudin is not more effective than heparin in preventing ischemic complications in patients undergoing coronary angioplasty for thrombus-containing lesions detected by angiography. Other approaches, perhaps involving potent anti-platelet agents, should be considered for patients with thrombus-containing lesions.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Coronary Thrombosis; Double-Blind Method; Female; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Ischemia; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

Direct thrombin inhibitors are a new class of drugs that may offer a more effective and potentially simpler alternative to heparin. Hirulog is a synthetic peptide based on the leech-derived compound hirudin and, like hirudin, is a highly specific, direct inhibitor of free and clot-bound thrombin.. TIMI 7 was a randomized, double-blind study of Hirulog, given with 325 mg/d aspirin to 410 patients with unstable angina. Patients received a constant infusion of Hirulog for 72 hours at one of four doses: 0.02 (n = 160), 0.25 (n = 81), 0.5 (n = 88), and 1.0 (n = 81) mg.kg-1.h-1. The primary efficacy end point was "unsatisfactory outcome," defined as death, nonfatal myocardial infarction (MI), rapid clinical deterioration, or recurrent ischemic pain at rest with ECG changes by 72 hours. Unsatisfactory outcome was not different among the four dose groups: 8.1%, 6.2%, 11.4%, and 6.2% (P = NS). However, the secondary end point of death or nonfatal MI through hospital discharge occurred in 10.0% of patients treated with 0.02 mg.kg-1.h-1 compared with 3.2% of patients treated with the three higher doses of Hirulog (0.25, 0.5, and 1.0 mg.kg-1.h-1, P = .008). Only 2 of 410 patients (0.5%) experienced a major hemorrhage attributed to Hirulog.. The direct thrombin inhibitor Hirulog is a promising new antithrombotic agent that deserves further study. The results of TIMI 7 lend support to the use of an antithrombin agent with aspirin in patients with unstable angina.

Topics: Adult; Aged; Angina, Unstable; Aspirin; Coronary Angiography; Dose-Response Relationship, Drug; Double-Blind Method; Female; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Myocardial Revascularization; Peptide Fragments; Pilot Projects; Recombinant Proteins; Thrombin

The use of bivalirudin versus unfractionated heparin monotherapy in patients without ST-segment-elevation myocardial infarction is not well defined.. The study population consisted of patients enrolled in the Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry with either non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease, who underwent percutaneous coronary intervention with either unfractionated heparin or bivalirudin monotherapy. Propensity score matching was used to adjust for baseline characteristics. The primary bleeding (in-hospital composite bleeding-access site bleeding, thrombolysis in myocardial infarction major/minor bleeding, or transfusion) and primary (in-hospital death/myocardial infarction) and secondary ischemic outcomes (death/myocardial infarction/unplanned repeat revascularization at 12 months) were evaluated. Propensity score matching yielded 1036 patients with non-ST-segment-elevation acute coronary syndromes and 2062 patients with stable ischemic heart disease. For the non-ST-segment-elevation acute coronary syndrome cohort, bivalirudin use was associated with lower bleeding (difference, -3.3% [-0.8% to -5.8%]; P=0.01; number need to treat=30) without increase in either primary (difference, 1.2% [4.1% to -1.8%]; P=0.45) or secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [1.3% to -1.3%]; P=1.00). Similarly, in the stable ischemic heart disease cohort, bivalirudin use was associated with lower bleeding (difference, -1.8% [-0.4% to -3.3%]; P=0.01; number need to treat=53) without increase in either primary (difference, 0.4% [2.3% to -1.5%]; P=0.70) or secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [0.7% to -0.7%]; P=1.00) when compared with unfractionated heparin monotherapy.. Among patients with non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease undergoing percutaneous coronary intervention, bivalirudin use during percutaneous coronary intervention when compared with unfractionated heparin monotherapy was associated with lower bleeding without significant increase in ischemic outcomes or stent thrombosis.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Cohort Studies; Electrocardiography; Female; Follow-Up Studies; Hemorrhage; Heparin; Hirudins; Humans; Incidence; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Recombinant Proteins; Registries; Risk Factors; Thrombosis; Treatment Outcome

This study sought to compared the use and effectiveness of bleeding avoidance strategies (BAS) by sex.. Women have higher rates of bleeding following percutaneous coronary intervention (PCI).. Among 570,777 men (67.5%) and women (32.5%) who underwent PCI in the National Cardiovascular Data Registry's CathPCI Registry between July 1, 2009 and March 31, 2011, in-hospital bleeding rates and the use of BAS (vascular closure devices, bivalirudin, radial approach, and their combinations) were assessed. The relative risk of bleeding for each BAS compared with no BAS was determined in women and men using multivariable logistic regressions adjusted for clinical characteristics and the propensity for receiving BAS. Finally, the absolute risk differences in bleeding associated with BAS were compared.. Overall, the use of any BAS differed slightly between women and men (75.4% vs. 75.7%, p = 0.01). When BAS was not used, women had significantly higher rates of bleeding than men (12.5% vs. 6.2%, p < 0.01). Both sexes had similar adjusted risk reductions of bleeding when any BAS was used (women, odds ratio: 0.60, 95% confidence interval [CI]: 0.57 to 0.63; men, odds ratio: 0.62, 95% CI: 0.59 to 0.65). Women and men had lower absolute bleeding risks with BAS; however, these absolute risk differences were greater in women (6.3% vs. 3.2%, p < 0.01).. Women continue to have almost twice the rate of bleeding following PCI. The use of any BAS was associated with a similarly lower risk of bleeding for men and women; however, the absolute risk differences were substantially higher in women. These data underscore the importance of applying effective strategies to limit post-PCI bleeding, especially in women.

Topics: Aged; Antithrombins; Blood Loss, Surgical; Female; Hemostasis, Surgical; Hirudins; Humans; Male; Middle Aged; Myocardial Ischemia; Patient Selection; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Hemorrhage; Practice Patterns, Physicians'; Recombinant Proteins; Registries; Retrospective Studies; Risk Assessment; Sex Factors; Treatment Outcome; United States

Antithrombins are among standard treatment agents for patients with non-ST-segment elevation acute coronary syndromes. We aimed to determine the association between time from emergency department (ED) presentation to treatment with an antithrombin and adverse cardiac events.. The study cohort was a subgroup of the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial, enrolled from March 1, 2005, to December 5, 2005. The ACUITY trial enrolled patients with moderate- and high-risk non-ST-segment elevation acute coronary syndromes and who were undergoing an early invasive strategy (<72 hours from randomization). All patients received an antithrombin (unfractionated heparin, low-molecular-weight heparin, or bivalirudin), in addition to other agents. A formal ED case report form was introduced in March 2005. Time from presentation to antithrombin initiation was evaluated as a continuous variable in hours. The endpoints were defined as major ischemic events (death, myocardial infarction, unplanned revascularization) or major bleeding within 30 days, or inhospital major bleeding. Logistic regression was used to adjust for demographics, severity of disease, comorbidities, and treatment differences.. Of the 2,722 patients enrolled with an ED case report form, complete time data were available in 2,632 (96%). Median time to antithrombin administration was 4.87 hours (interquartile range 2.67 to 9.83). After multivariable analysis, there was no association of major ischemic events with log time (hours) to antithrombin treatment (adjusted odds ratio [OR] 0.99; 95% confidence interval [CI] 0.97 to 1.01). There was an increase in major bleeding at 30 days and inhospital major bleeding complications with longer log time (hours) to antithrombin initiation (adjusted OR 1.44, 95% CI 1.15 to 1.80; OR 1.43, 95% CI 1.13 to 1.83, respectively).. In this study of patients with non-ST-segment elevation acute coronary syndromes who were undergoing an early invasive management strategy, we were unable to demonstrate an association between adverse ischemic outcomes with the timing of antithrombin administration. However, there was an increase in bleeding outcomes as time to antithrombin administration increased.

Topics: Acute Coronary Syndrome; Aged; Antithrombins; Confidence Intervals; Emergency Service, Hospital; Female; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Odds Ratio; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Time Factors

Both ischemic and hemorrhagic complications increase mortality rate in acute coronary syndromes. Their frequency and relative importance vary according to individual patient risk profiles. We sought to develop prognostic models for the risk of myocardial infarction (MI) and major bleeding to assess their impact on risk of death and to examine the manner in which alternative antithrombotic regimens affect these risks in individual patients.. The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial randomized 13 819 patients with acute coronary syndrome to heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. By logistic regression, there were 5 independent predictors of MI within 30 days (n=705; 5.1%) and 8 independent predictors of major bleeding (n=645; 4.7%), only 2 of which were common to both event types. In a covariate-adjusted, time-updated Cox regression model, both MI and major bleeding significantly affected subsequent mortality rate (hazard ratios, 2.7 and 2.9, respectively; both P<0.001). Treatment with bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor was associated with a nonsignificant 8% increase in MI and a highly significant 50% decrease in major bleeding. Given the individual patient risk profiles and the fact that bivalirudin prevented approximately 6 major bleeds for each MI that might occur from its use, the estimated reduction in bleeding was greater than the estimated increase in MI by bivalirudin alone rather than heparin plus a glycoprotein IIb/IIIa inhibitor for nearly all patients.. Consideration of the individual patient risk profile for MI and major bleeding and the relative treatment effects of alternative pharmacotherapies permits personalized decision making to optimize therapy of patients with acute coronary syndrome.. clinicaltrials.gov Identifier: NCT00093158.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Predictive Value of Tests; Prognosis; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Risk Factors

Topics: Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Factors; Time Factors

The temporary total artificial heart (TAH-t) has emerged as an effective bridge to transplantation for individuals with biventricular failure. Implantation of a TAH-t creates a hypercoagulable state requiring a multidrug approach that includes low-dose unfractionated heparin (UFH) in order to minimize thromboembolism. A concern with UFH is the development of heparin-dependent antibodies, which develop in up to 50% of patients receiving the drug as part of cardiopulmonary bypass. If UFH therapy continues postoperatively, the risk of heparin-induced thrombocytopenia approaches 3%. Small investigations have demonstrated that bivalirudin, given as a bolus of 0.75-1 mg/kg followed by an infusion at 1.75-2.5 mg/kg/hour, is an effective alternative to UFH for therapeutic anticoagulation during coronary artery bypass surgery, valve replacement, or both. We describe a series of five adults (age range 24-58 yrs) who received bivalirudin as an alternative to low-dose UFH after TAH-t implantation. None of the patients had documented heparin-induced thrombocytopenia. Treatment was started at the discretion of the treating physician, and adjustments were based principally on the results of thromboelastography. Additional general monitoring included activated partial thromboplastin time, prothrombin time, international normalized ratio, fibrinogen, D-dimer, platelet count, hemoglobin, hematocrit, and platelet aggregation studies. Bivalirudin therapy was continued until successful warfarin implementation. All five patients received bivalirudin in addition to standard antithrombotic therapy. Bivalirudin treatment started at a dosage of 0.005 or 0.01 mg/kg/hour with titration to maintain normocoagulability, which occurred (without concomitant warfarin therapy) within the dosage range of 0.01-0.02 mg/kg/hour. Duration of TAH-t implantation was a mean of 38.8 days (range 25-60 days), and bivalirudin was continued for a mean of 15.2 days (range 7-24 days). No major hemorrhagic events occurred during treatment, and all patients successfully transitioned to warfarin therapy. Low-dose bivalirudin, as an alternative to UFH, maintained normocoagulability after TAH-t implantation. Further investigation is warranted to define the role and dosing of bivalirudin in this situation.

Topics: Anticoagulants; Antithrombins; Cardiomyopathy, Dilated; Heart Transplantation; Heart, Artificial; Hirudins; Humans; Intraoperative Complications; Male; Middle Aged; Myocardial Ischemia; Partial Thromboplastin Time; Peptide Fragments; Prosthesis Implantation; Recombinant Proteins; Young Adult

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Combined Modality Therapy; Drug Therapy, Combination; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Research Design; Treatment Outcome

A patient with triple heart valve disease, heparin-induced thrombocytopenia, and terminal renal insufficiency was treated successfully using lepirudin for anticoagulation of cardiopulmonary bypass (CPB) and during the postoperative course. Anticoagulatory monitoring was performed with ecarin clotting time during CPB and aPTT postoperatively.

Topics: Aged; Anticoagulants; Cardiopulmonary Bypass; Female; Follow-Up Studies; Heart Failure; Heparin; Hirudins; Humans; Kidney Failure, Chronic; Myocardial Ischemia; Recombinant Proteins; Thrombocytopenia

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Drug Therapy, Combination; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins

Thrombin exerts multiple actions on cardiomyocytes leading to increased intracellular Na+ and Ca2+ concentrations, and to activation of a Ca2+-independent PLA2, and has been proposed to favor the genesis of arrhythmias and ischemic injury in acute coronary syndromes. However, the influence of thrombin on cardiomyocyte cell death during ischemia-reperfusion has not been studied. A beneficial influence of low thrombin concentrations has been described in other cell types. HL-1 cardiomyocytes were subjected to simulated ischemia (SI) and reperfusion (SR) and cell death was assessed by means of LDH release to the incubation media. Thrombin dose-dependently increased cell death in normoxic cells, in cells subjected to SI, and in cells subjected to SR (by 20+/-8%, 95+/-32% and 35+/-9%, respectively, at 100 U/ml). The effects of thrombin were associated to increased cytosolic Ca2+ overload, mimicked by 100 microM PAR-1 agonist peptide SFLLRNPNDKYEPF, and reversed by the direct thrombin inhibitor lepirudin (IC50=1.3+/-0.2 microg/ml). The presence of thrombin during simulated ischemia-reperfusion increases cardiomyocyte cell death by a mechanism that involves activation of PAR-1 receptors and can be prevented by the direct thrombin inhibitor lepirudin.

Topics: Animals; Calcium Signaling; Cell Death; Cells, Cultured; Digitonin; Hirudins; Lactate Dehydrogenases; Mice; Mice, Transgenic; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocytes, Cardiac; Receptors, Thrombin; Recombinant Proteins; Thrombin

The combination of glycoprotein (GP) IIb-IIIa inhibition and direct thrombin inhibition (DTI) with bivalirudin (Angiomax, The Medicines Company, Cambridge, Massachusetts) have shown ischemic and hemorrhagic outcomes benefit in coronary interventions and may have similar benefits in percutaneous peripheral interventions (PPI). The high incidence of diabetes, chronic renal disease, platelet dysfunction, hypercoagulability, inflammation and a thrombus-rich environment make a GP IIb-IIIa and DTI combination with tirofiban (Aggrastat Merck and Company, Inc., Whitehouse Station, New Jersey) an attractive anticoagulation strategy in the PPI treatment of critical limb ischemia (CLI).. Between May 1, 2001 and January 31, 2003, a CLI treatment group of 149 patients received PPI with bivalirudin (0.75 mg per kg bolus with 1.75 mg per kg per hour periprocedural infusion) and tirofiban (10 mcg per kg per minute bolus with 12-hour 0.1 mcg per kg per minute infusion) as an anticoagulation and antiplatelet strategy, and were compared to a matched unfractionated heparin (UFH) control group without GP IIb-IIIa inhibitors. Clinical and hemostasis outcomes were analyzed, including distal embolization (DE).. Procedural success was 95.9% and 97.3% in the UFH control group and DTI-GP IIb-IIIa group, respectively. Significant differences were observed in the sheath removal time < 2 hours (60.5% UFH group versus 19.4% DTI-GP IIb-IIIa group; p = < 0.0001). Vascular closure devices were used equally in both groups. No statistical significance was observed in major and minor complications, femoral access complications, acute (< 48 hours) or subacute (30 days) vessel thrombosis, and 6-month duplex ultrasound restenosis rate between the DTI-GP IIb-IIIa versus the UFH group. A trend towards statistical significance was observed in the 6-month secondary re-intervention and limb salvage rates (10.7% versus 18.8%; p = 0.0501 and 93.9% versus 88.5%; p = 0.053) in the DTI-GP IIb-IIIa versus the UFH group, respectively. Angiographically relevant DE occurred in 4 of 149 (1.3%) and 8 of 149 (5.4%) of the bivalirudin-tirofiban and UFH groups, respectively.. The combination of DTI with bivalirudin and GP IIb-IIIa inhibition with tirofiban is a safe and feasible alternative anticoagulation and antiplatelet strategy in PPI, and may offer improved clinical and hemostasis outcomes in treating CLI. A larger, prospective randomized trial is warranted.

Topics: Acute Disease; Aged; Angioplasty, Balloon; Anticoagulants; Feasibility Studies; Female; Follow-Up Studies; Hirudins; Humans; Ischemia; Leg; Male; Myocardial Ischemia; Peptide Fragments; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Retrospective Studies; Thrombin; Tirofiban; Treatment Outcome; Tyrosine

Topics: Anaphylaxis; Fibrinolytic Agents; Hirudins; Humans; Myocardial Ischemia; Recombinant Proteins; Time Factors

Activation of the coagulation cascade during myocardial ischemia and reperfusion may contribute to the post-ischemic inflammatory response, mostly via generation of thrombin. We assessed the effect of the anticoagulants unfractionated heparin (UFH), low molecular weight heparin (LMWH) and r-hirudin on leukocyte adhesion and emigration after ischemia and reperfusion in rats. The rat cremaster muscle was prepared for intravital microscopy. One hundred and twenty minutes of ischemia were followed by 90 min of reperfusion. Saline (control), UFH, LMWH or r-hirudin were given 15 min prior to reperfusion and infused for the rest of the observation period. Dosages per kilogram of body weight were (bolus, infusion): saline, 3 ml, 3 ml/h; UFH, 400 IU, 100 IU/h; LMWH, 100 IU, 3 ml/h saline; or r-hirudin, 0.3 mg, 0.15 mg/h. In collecting venules, rolling, adherent, and extravasated leukocytes were counted from recordings of the intravital microscopy. All three anticoagulants similarly attenuated post-ischemic endothelial leukocyte adhesion. In contrast, emigration of leukocytes was only attenuated by r-hirudin. The emigration efficiency of adherent leukocytes (control, 1.21) was unchanged after UFH (1.74), and LMWH (1.51) but decreased after r-hirudin treatment (0.12). The different efficacy of the three anticoagulants in affecting emigration of adherent leukocytes suggests a specific role for the direct thrombin inhibitor r-hirudin in attenuating the post-ischemic inflammatory response. This effect may contribute to the benefits of direct thrombin inhibitors seen in clinical studies after treatment for acute coronary syndromes.

Topics: Animals; Cell Adhesion; Cell Movement; Endothelium; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Leukocytes; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Rats; Rats, Sprague-Dawley

With advances in therapy of acute coronary syndromes, repetitive exposure to heparin has become commonplace. Consequently, the incidence of heparin-induced thrombocytopenia has risen. Limited strategies for management exist, and new thrombin inhibitors may provide safe alternatives to heparin. Two patients with documented heparin-induced thrombocytopenia underwent revascularization using a new thrombin inhibitor (Bivalirudin [Angiomax, Medicines Co, Cambridge, MA]) for anticoagulation. Both patients had uneventful perioperative hospitalizations. Thrombin inhibition with Bivalirudin (Angiomax) may provide a safe reliable alternative to heparin use in cardiac surgery [corrected].

Topics: Aged; Coronary Artery Bypass; Female; Fibrinolytic Agents; Follow-Up Studies; Heart-Lung Machine; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Revascularization; Risk Assessment; Severity of Illness Index; Thrombocytopenia; Treatment Outcome

The aim of this retrospective, observational analysis was to compare the efficacy and safety of 3 antithrombotic regimens: bivalirudin, eptifibatide plus heparin, and heparin alone, with emphasis on preventing interventional procedural creatinine kinase-MB fraction (CK-MB) release, and consequently, myocardial necrosis.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Drug Therapy, Combination; Eptifibatide; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Peptides; Recombinant Proteins; Retrospective Studies; Treatment Outcome

Topics: Acute Disease; Blood Coagulation; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardial Ischemia; Thrombin

Thrombin plays a role in mediating ischemic injury and cardiac arrhythmias, but the mechanisms involved are poorly understood. Because voltage-gated sodium channels (VGSCs) have not previously been considered, putative effects of thrombin on VGSC function were investigated in human isolated cardiomyocytes.. Sodium current (I(Na)) was recorded by the whole-cell patch-clamp method. Thrombin increased peak I(Na) amplitude in an activity-dependent manner, from 1 to 100 U/mL, with an apparent EC50 of 91+/-16 U/mL. When tested at 32 U/mL, thrombin-increased I(Na) was abolished by tetrodotoxin (50 micromol/L). Thrombin effects on I(Na) were reversible and repeatable, and 100 U/mL doubled peak I(Na) amplitude. Thrombin (32 U/mL) shifted I(Na) activation to hyperpolarized potentials without affecting steady-state inactivation, producing unusually large increases in window current. Hirudin (320 U/mL) or haloenol lactone suicide substrate (10 micromol/L) failed to significantly affect these effects of thrombin. In current-clamped cardiomyocytes, thrombin (32 U/mL) depolarized resting membrane potential by 10 mV.. Facilitation of VGSC activation causing large increases in window current is a major mechanism by which thrombin may promote ischemic sodium loading and injury.

Topics: Action Potentials; Aged; Cells, Cultured; Dose-Response Relationship, Drug; Heart; Hirudins; Humans; Ion Channel Gating; Ion Transport; Membrane Potentials; Middle Aged; Myocardial Ischemia; Myocardium; Naphthalenes; Patch-Clamp Techniques; Pyrones; Sodium; Sodium Channels; Thrombin

Topics: Aged; Angina, Unstable; Angioplasty, Balloon, Coronary; Cardiac Catheterization; Female; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Ischemia; Recombinant Proteins; Secondary Prevention; Syndrome

Functional inhibition of tissue factor (TF) has been shown to improve coronary blood flow after myocardial ischemia/reperfusion (I/R) injury. TF initiates the coagulation protease cascade, resulting in the generation of the serine protease thrombin and fibrin deposition. Thrombin can also contribute to an inflammatory response by activating various cell types, including vascular endothelial cells. We used a rabbit coronary ligation model to investigate the role of TF in acute myocardial I/R injury. At-risk areas of myocardium showed increased TF expression in the sarcolemma of cardiomyocytes, which was associated with a low level of extravascular fibrin deposition. Functional inhibition of TF activity with an anti-rabbit TF monoclonal antibody administered either 15 minutes before or 30 minutes after coronary ligation reduced infarct size by 61% (P = 0.004) and 44% (P = 0.014), respectively. Similarly, we found that inhibition of thrombin with hirudin reduced infarct size by 59% (P = 0.014). In contrast, defibrinogenating the rabbits with ancrod had no effect on infarct size, suggesting that fibrin deposition does not significantly contribute to infarct size. Functional inhibition of thrombin reduced chemokine expression and inhibition of either TF or thrombin reduced leukocyte infiltration. We propose that cardiomyocyte TF initiates extravascular thrombin generation, which enhances inflammation and injury during myocardial I/R.

Topics: Animals; Antibodies, Monoclonal; Antithrombins; Cell Movement; Chemokines; Fibrin; Fibrinogen; Hirudins; Microscopy, Electron; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocarditis; Myocardium; Neutrophils; Rabbits; Thrombin; Thromboplastin

Hirudin is a peptide of 65 aminoacids extracted from the leech which very specifically inhibits the action of thrombin. Molecular engineering techniques have made it available for therapeutic usage. Experimental data would suggest that hirudin was the drug of choice for the prevention of coronary thrombosis and recurrences, an indication where heparin is not always effective. Despite well organised studies of tolerance and dosage, three large scale clinical trials have had to be interrupted because of a high incidence of severe bleeding complications. The therapeutic margin of hirudin is therefore as low as that of heparin. The initial results of trials using lower doses have not shown hirudin to be effective than heparin in the prevention of critical events in the long term. The reasons for this relative failure are two-fold: either hirudin and molecules with similar modes of action such as Hirulog are less active in vivo than in vitro, possibly due to the fact that they block the activation of the C protein, a powerful natural antithrombotic mechanism, or, the target of hirudin: thrombin, does not play the fundamental role attributed to it in arterial thrombosis. The good results observed with molecules which inhibit platelet aggregation would suggest a dominant role of the platelets.

Topics: Anticoagulants; Antithrombins; Dose-Response Relationship, Drug; Drug Administration Schedule; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardial Ischemia; Pilot Projects; Treatment Failure

Topics: Aged; Blood Coagulation Factors; Female; Hemorrhagic Disorders; Hirudin Therapy; Hirudins; Humans; Myocardial Ischemia; Randomized Controlled Trials as Topic; Recombinant Proteins