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1.
Am J Cardiol ; 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31474328

RESUMO

Whether patients with atrial fibrillation (AF) and thyroid disease are clinically distinct from those with AF and no thyroid disease is unknown. Furthermore, the effectiveness of anticoagulation for prevention of AF-related thromboembolic events in patients with thyroid disease has not been adequately studied. Patients enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation, which compared apixaban with warfarin in patients with AF (n = 18,201), were categorized by thyroid disease history at randomization (hypothyroidism, hyperthyroidism, and no thyroid disease). Adjusted hazard ratios derived from Cox models were used to compare outcomes by thyroid disease history. Associations between randomized treatment and outcomes by thyroid disease history were examined using Cox models with interaction terms. A total of 18,021/18,201 (99%) patients had available thyroid disease history at randomization: 1,656 (9%) had hypothyroidism, 321 (2%) had hyperthyroidism, and 16,044 (89%) had no thyroid disease. When compared with those without a history of thyroid disease, patients with hypo- or hyperthyroidism were more likely to be female (60.4% vs 32.1%; 52.0% vs 32.1%; both p <0.0001). Patients with hypothyroidism were older (73 vs 70 years, p <0.0001) and more likely to have had previous falls (8.7% vs 4.3%, p <0.0001). There was no difference in clinical outcomes by thyroid disease history. The benefit of apixaban compared with warfarin was similar regardless of thyroid disease history (interaction p >0.10). In conclusion, despite differences in baseline characteristics of patients with and without thyroid disease, their clinical outcomes were similar. The benefit of apixban compared with warfarin was preserved regardless of thyroid disease history.

2.
Rev Port Cardiol ; 2019 Sep 03.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31492459

RESUMO

The Editors' Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31512201

RESUMO

Diabetes mellitus (DM) and abnormal glucose metabolism are associated with cardiovascular (CV) disease. We investigated the prevalence and prognostic importance of dysglycaemia in patients with acute coronary syndromes (ACS) in the PLATelet inhibition and patient Outcomes (PLATO) trial. Diabetes was defined as known diabetes or HbA1c ≥ 6.5% or non-fasting glucose ≥ 11.1 mmol/L on admission, prediabetes as HbA1c ≥ 5.7% but < 6.5%, and no diabetes as HbA1c < 5.7%. The primary endpoint was the composite of CV death, spontaneous myocardial infarction type 1 (sMI) or stroke at 12 months. Multivariable Cox regression models, adjusting for baseline characteristics, and biomarkers NT-proBNP and troponin I, were used to explore the association between glycaemia and outcome. On admission, 16,007 (86.1%) patients had HbA1c and/or glucose levels available and were subdivided into DM 38.5% (6160) (1501 patients had no previous DM diagnosis), prediabetes 38.8% (6210), and no DM 22.7% (3637). Kaplan Meier event rates at 12 months for CV death, sMI or stroke per subgroups were 14.5% (832), 9.0% (522), and 8.5% (293), respectively with multivariable adjusted HRs, versus no diabetes, for diabetes: 1.71 (1.50-1.95) and for prediabetes 1.03 (0.90-1.19). Corresponding event rates for CV death were 6.9% (391), 3.4% (195) and 3.0% (102), respectively, with adjusted HRs for patients with DM of: 1.92 (1.42-2.60) and for prediabetes 1.02 (0.79-1.32). Abnormal glucose metabolism is common in ACS patients, but only patients with definite DM have an increased CV risk, indicating that prediabetes is not immediately associated with worse CV outcomes.

4.
Rev. urug. cardiol ; 34(2): 11-36, ago. 2019.
Artigo em Espanhol | LILACS-Express | ID: biblio-1014545

RESUMO

Resumen: La Red de Editores de la Sociedad Europea de Cardiología (ESC, por su sigla en inglés) constituye un foro dinámico dedicado a discusiones editoriales y respalda las recomendaciones del Comité Internacional de Editores de Revistas Médicas (ICMJE, por su sigla en inglés) destinadas a mejorar la calidad científica de las revistas biomédicas. La paternidad literaria confiere crédito, además de importantes recompensas académicas. Recientemente, sin embargo, el ICMJE ha destacado que la autoría también exige que los autores sean responsables y se hagan cargo de lo que publican. Estas cuestiones ahora están cubiertas por el nuevo (cuarto) criterio para la autoría. Los autores deben aceptar hacerse responsables de lo que escriben y garantizar un adecuado enfoque de las cuestiones concernientes a la precisión e integridad de todo el trabajo. Esta revisión analiza las implicancias de este cambio de paradigma en los requisitos de autoría con el objetivo de aumentar la conciencia sobre las buenas prácticas científicas y editoriales.


Summary: The Editors´ Network of the European Society of Cardiology provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the International Committee of Medical Journal Editors emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.


Resumo: A Rede de Editores da Sociedade Europeia de Cardiologia é um fórum dinâmico para discussões editoriais e apoia as recomendações do Comitê Internacional de Editores de Revistas Médicas, visando melhorar a qualidade científica das revistas biomédicas. A autoria confere crédito, além de importantes recompensas acadêmicas. Recentemente, no entanto, o Comitê Internacional de Editores de Revistas Médicas enfatizou que a autoria também requer que os autores sejam responsáveis do que escrevem e se encarreguem do que publicam. Essas questões agora estão cobertas pelo novo (quarto) critério de autoria. Os autores devem concordar em ser responsáveis e garantir que as questões relativas à precisão e integridade de todo o trabalho sejam abordadas de maneira apropriada. Esta revisão discute as implicações dessa mudança de paradigma nos requisitos de autoria, com o objetivo de aumentar a conscientização sobre as boas práticas científicas e editoriais.

5.
Platelets ; : 1-8, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31389740

RESUMO

Extracellular vesicles (EV) act as a cellular communication tool by carrying lipids, proteins and micro RNA (miR) between cells, thereby playing a pivotal role in thromboembolic processes. The effect of P2Y12 inhibitors on pro-coagulatory, phosphatidylserine (PS)-expressing EV has been investigated previously, but only in vitro or during confounding clinical conditions, such as acute coronary syndrome. Hence, we enrolled 62 consecutive patients 12 month after percutaneous coronary intervention and stent implantation and consequent treatment with dual-antiplatelet therapy consisting of low-dose aspirin and P2Y12 inhibitors. Blood for platelet function testing and EV and miR measurements was taken on the last day of P2Y12 inhibitor intake (baseline, on-treatment) and 10, 30 and 180 days thereafter (off-treatment). We did not observe any influence of P2Y12 inhibitors on the levels of PS-EV or EV sub-population from platelets, erythrocytes, monocytes or endothelial cells, respectively. There was no relationship between platelet function and EV levels in plasma. However, the association of miR-21 and miR-150 with platelet EVs was significantly different between on- and off-treatment measurements. Hence, our study suggests no influence of P2Y12 inhibition on the count of EVs in plasma, but on the potential cargo of platelet-derived EV.

6.
Thromb Haemost ; 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31421642

RESUMO

As the number of, and the indications for, structural heart interventions are increasing worldwide, the optimal secondary prevention to reduce device thrombosis is becoming more important. To date, most of the recommendations are empiric. The current review discusses mechanisms behind device-related thrombosis, the available evidence with regard to antithrombotic regimen after cardiac device implantation, as well as providing an algorithm for identification of risk factors for device thrombogenicity and for management of device thrombosis after implantation of patent foramen ovale and left atrial appendage occluders, MitraClips/transcatheter mitral valve replacement, pacemaker leads, and left ventricular assist devices. Of note, the topic of antithrombotic therapy and thrombogenicity of prostheses in aortic position (transcatheter aortic valve replacement, surgical, mechanical, and bioprostheses) is not part of the present article and is discussed in detail in other contemporary focused articles.

7.
Thromb Haemost ; 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31421643

RESUMO

Microribonucleic acids (miRs) are small, noncoding ribonucleic acids (RNAs), which play an important role in the regulation of platelet function and activity. Several studies proposed a mechanistic role of platelet-related miRs in the pathophysiology of coronary artery disease (CAD) and atherothrombosis. Circulating, platelet-related miRs have been proposed as diagnostic, prognostic, as well as treatment response biomarkers in CAD and acute coronary syndrome (ACS). In this review, we summarize recent studies on the role of platelet-related miRs in the regulation of platelet function and activity. Furthermore, we review the studies investigating the role of platelet-related miRs as biomarkers in patients with CAD and ACS.

8.
J Am Coll Cardiol ; 74(1): 83-99, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31272556

RESUMO

Most patients with atrial fibrillation (AF) and risk factors for stroke require oral anticoagulation (OAC) to decrease the risk of stroke or systemic embolism. This is now best achieved with direct oral anticoagulants that decrease the risk of intracranial bleeding compared with vitamin K antagonists. Of note, approximately 5% to 10% of patients undergoing percutaneous coronary intervention have AF, which complicates antithrombotic therapy in daily practice, because the guidelines recommend that these patients also receive dual antiplatelet therapy (DAPT) to reduce the risk of ischemic complications. However, combining OAC with DAPT, a strategy also known as triple antithrombotic therapy, is known to increase the risk of bleeding compared with the use of OAC or DAPT alone. Studies of direct oral anticoagulants are now emerging that show the favorable safety profile of double antithrombotic therapy with OAC and a P2Y12 inhibitor in comparison with triple antithrombotic therapy including the use of vitamin K antagonists. The scope of this review is to provide an update on this topic as well as to discuss future directions in the management of antithrombotic therapy after percutaneous coronary intervention in AF patients requiring chronic OAC.

9.
BMJ Open ; 9(7): e028311, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340965

RESUMO

OBJECTIVES: There is sparse information on the safety of early primary discharge from the emergency department (ED) after rule-out of myocardial infarction in suspected acute coronary syndrome (ACS). This prospective registry aimed to confirm randomised study results in patients at low-to-intermediate risk, with a broader spectrum of symptoms, across different institutional standards and with a range of local troponin assays including high-sensitivity cTn (hs-cTn), cardiac troponin (cTn) and point-of-care troponin (POC Tn). DESIGN: Prospective, multicentre European registry. SETTING: 18 emergency departments in nine European countries (Germany, Austria, Switzerland, France, Spain, UK, Turkey, Lithuania and Hungary) PARTICIPANTS: The final study cohort consisted of 2294 patients (57.2% males, median age 57 years) with suspected ACS. INTERVENTIONS: Using the new dual markers strategy, 1477 patients were eligible for direct discharge, which was realised in 974 (42.5%) of patients. MAIN OUTCOME MEASURES: The primary endpoint was all-cause mortality at 30 days. RESULTS: Compared with conventional workup after dual marker measurement, the median length of ED stay was 60 min shorter (228 min, 95% CI: 219 to 239 min vs 288 min, 95% CI: 279 to 300 min) in the primary dual marker strategy (DMS) discharge group. All-cause mortality was 0.1% (95% CI: 0% to 0.6%) in the primary DMS discharge group versus 1.1% (95% CI: 0.6% to 1.8%) in the conventional workup group after dual marker measurement. Conventional workup instead of discharge despite negative DMS biomarkers was observed in 503 patients (21.9%) and associated with higher prevalence of ACS (17.1% vs 0.9%, p<0.001), cardiac diagnoses (55.2% vs 23.5%, p<0.001) and risk factors (p<0.01), but with a similar all-cause mortality of 0.2% (95% CI: 0% to 1.1%) versus primary DMS discharge (p=0.64). CONCLUSIONS: Copeptin on top of cardiac troponin supports safe discharge in patients with chest pain or other symptoms suggestive of ACS under routine conditions with the use of a broad spectrum of local standard POC, conventional and high-sensitivity troponin assays. TRIAL REGISTRATION NUMBER: NCT02490969.

10.
Clin Res Cardiol ; 2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31256260

RESUMO

OBJECTIVE: The emergency medical service (EMS) provides rapid pre-hospital diagnosis and transportation in ST-elevation myocardial infarction (STEMI) systems of care. Aim of the study was to assess temporal and regional characteristics of EMS-related delays in a metropolitan STEMI network. METHODS: Patient call-to-arrival of EMS at site (call-to-site), transportation time from site to hospital (site-to-door), call-to-door, patient's location, month, weekday, and hour of EMS activation were recorded in 4751 patients referred to a tertiary center with suspicion of STEMI. RESULTS: Median call-to-site, site-to-door, and call-to-door times were 9 (7-12), 39 (31-48), and 49 (41-59) minutes, respectively. The shortest transportation times were noted between 08:00 and 16:00 and in general on Sundays. They were significantly prolonged between midnight and 04:00, whereby the longest difference did not exceed 4 min in median. Patient's site of call had a major impact on transportation times, which were shorter in Central and Western districts as compared to Southern and Eastern districts of Vienna (p < 0.001 between-group difference for call-to-site, site-to-door, and call-to-door). After multivariable adjustment, patient's site of call was an independent predictor of call-to-site delay (p < 0.001). Moreover, age and hour of EMS activation were the strongest predictors of call-to-site, site-to-door, and call-to-door delays (p < 0.05). CONCLUSION: In our Viennese STEMI network, the strongest determinants of pre-hospital EMS-related transportation delays were patient's site of call, patient's age, and hour of EMS activation. Due to the significant but small median time delays, which are within the guideline-recommended time intervals, no impact on clinical outcome can be expected.

11.
Arch Cardiol Mex ; 89(2): 105-111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314006

RESUMO

The Editors' Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new -(fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.

12.
Eur J Clin Invest ; 49(9): e13157, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31318979

RESUMO

BACKGROUND: Increased platelet turnover and high platelet reactivity are associated with short-term major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) or stable coronary artery disease (SCAD). We investigated the impact of platelet turnover on long-term MACE. METHODS: Consecutive patients presenting with ACS or SCAD undergoing PCI between 2009 and 2010 were included. All patients received clopidogrel and aspirin as dual antithrombotic therapy regimen. Multivariable Cox proportional hazard models were applied to assess the prognostic impact of platelet turnover (reticulated platelet count [RPC], mean platelet volume [MPV]) and function on long-term MACE, a composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke. RESULTS: In total, 477 patients were eligible. Mean age was 64.3 ± 12.7 years, 68.8% were male. Median follow-up was 5.8 (IQR 4.2-6.5) years. Median RPC was 7.6 (IQR 5.6-10.4) g/L and median MPV was 10.7 (IQR 10.1-11.3) fL. In univariable analysis, RPC was associated with MACE, both as continuous (HR 1.064 [95%CI 1.021-1.111]; P = .006) and dichotomized (HR 1.693 [95%CI 1.156-2.481]; P = .006) variable. After adjustment, continuous RPC (HR 1.055 [95%CI 1.012-1.099]; P = .010) and dichotomized RPC (HR 1.716 [95%CI 1.152-2.559]; P = .007) remained significantly associated with MACE. Neither MPV nor platelet function testing was associated with long-term adverse outcome. CONCLUSION: Increased platelet turnover is associated with long-term adverse outcome in patients with coronary artery disease undergoing PCI. Platelet turnover represents a new marker of atherothrombotic risk and might help to guide composition or duration of antiplatelet therapy.

14.
Thromb Haemost ; 119(9): 1394-1402, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31291665

RESUMO

Monocytes are activated in inflammatory conditions via a variety of cytokine receptors as well as in a procoagulatory setting through thrombin, acting upon protease-activated receptors (PARs). This study investigated the expression pattern of PAR1 and PAR3 on human monocyte subsets. Furthermore, a possible regulation of the expression of PAR1 and PAR3 in these cells by inflammatory activation were studied. CD16+ monocytes showed significantly higher levels of PAR1 and PAR3 as compared with CD16- monocytes. Ex vivo treatment of whole blood with lipopolysaccharide (LPS) increased PAR1 and PAR3 messenger ribonucleic acid (mRNA) in human monocytes. In addition, increase of PAR1 was seen in all three subsets upon LPS treatment, whereas PAR3 increased significantly only in CD16- monocytes and nonclassical CD16+ monocytes. Protein levels of PAR1 and PAR3 significantly increased on monocytes in vivo in human endotoxemia 1 hour after LPS infusion. PAR1 increased significantly in CD16- monocytes and nonclassical CD16+ monocytes. In this in vivo model, PAR3 was also significantly elevated in CD16- monocytes and increased slightly albeit not significantly in CD16+ monocytes. Endotoxemia increased plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) expression in monocytes in humans. Pretreatment of healthy volunteers with the PAR1 antagonist vorapaxar blocked the increase in PAI-1 but not the increase in TF. We here provide new evidence for a critical role for monocytes as cellular mediators that contribute to the activation of coagulation in diseases characterized by an inflammatory state.

15.
Eur J Prev Cardiol ; : 2047487319852809, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31154828

RESUMO

AIMS: Obesity defined by body mass index (BMI) is characterized by better prognosis and lower plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure. We assessed whether another anthropometric measure, per cent body fat (PBF), reveals different associations with outcome and heart failure biomarkers (NT-proBNP, high-sensitivity troponin T (hs-TnT), soluble suppression of tumorigenesis-2 (sST2)). METHODS: In an individual patient dataset, BMI was calculated as weight (kg)/height (m) 2 , and PBF through the Jackson-Pollock and Gallagher equations. RESULTS: Out of 6468 patients (median 68 years, 78% men, 76% ischaemic heart failure, 90% reduced ejection fraction), 24% died over 2.2 years (1.5-2.9), 17% from cardiovascular death. Median PBF was 26.9% (22.4-33.0%) with the Jackson-Pollock equation, and 28.0% (23.8-33.5%) with the Gallagher equation, with an extremely strong correlation ( r = 0.996, p < 0.001). Patients in the first PBF tertile had the worst prognosis, while patients in the second and third tertile had similar survival. The risks of all-cause and cardiovascular death decreased by up to 36% and 27%, respectively, per each doubling of PBF. Furthermore, prognosis was better in the second or third PBF tertiles than in the first tertile regardless of model variables. Both BMI and PBF were inverse predictors of NT-proBNP, but not hs-TnT. In obese patients (BMI ≥ 30 kg/m2, third PBF tertile), hs-TnT and sST2, but not NT-proBNP, independently predicted outcome. CONCLUSION: In parallel with increasing BMI or PBF there is an improvement in patient prognosis and a decrease in NT-proBNP, but not hs-TnT or sST2. hs-TnT or sST2 are stronger predictors of outcome than NT-proBNP among obese patients.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31198930

RESUMO

AIM: The combination of oral anticoagulation with a P2Y12 inhibitor and aspirin in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) is associated with a high bleeding risk. Dual antithrombotic therapy (DAT) with omission of aspirin is a promising option to reduce bleedings, but carries a yet unknown risk of ischemic events. We therefore sought to systematically review and analyse randomized controlled trials investigating DAT versus triple antithrombotic therapy (TAT) in patients with AF following PCI and/or acute coronary syndrome (ACS). METHODS AND RESULTS: We included 4 trials with overall 9317 patients (5039 DAT, 4278 TAT) in our analysis. DAT was associated with a significant reduction in thrombolysis in myocardial infarction (TIMI) major bleeding (HR 0.52 [95% CI 0.42 - 0.65]; p = 0.0001), while the composite trial-defined ischemic endpoint did not differ significantly between DAT and TAT (HR 0.98 [95% CI 0.79 - 1.22]; p = 0.88). There was also no difference regarding the occurrence of myocardial infarction (MI; HR 1.16 [95% CI 0.92 - 1.46]; p = 0.21) or stent thrombosis (HR 1.25 [95% CI 0.69 - 2.26]; p = 0.46). Absolute numbers for MI were 131/4278 (3.1%) with TAT and 182/5039 (3.6%) with DAT, and for stent thrombosis 32/4278 (0.75%) and 52/5039 (1%), respectively. A post-hoc power calculation based on the size and event rate of this meta-analysis revealed 80% power to detect a 37% and 100% increase in MI and stent thrombosis, respectively. CONCLUSION: DAT significantly reduces bleedings compared to TAT and seems to have a similar effect in preventing ischemic endpoints in AF patients post PCI or ACS. Future investigations are needed to determine its applicability specifically in patients with high risk of ischemic outcomes.

17.
Circ Cardiovasc Interv ; 12(6): e007661, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31167601

RESUMO

Background It is unclear whether atrial fibrillation (AF) influences prognosis in patients with cardiogenic shock and multivessel disease. We aimed to investigate the prognostic impact of AF in patients with cardiogenic shock complicating acute myocardial infarction. Methods and Results In a subanalysis of the CULPRIT-SHOCK trial (Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock), patients were grouped according to the presence of AF during index hospital stay. The primary end point was all-cause death at 30 days, and the key secondary end point was all-cause death at 1 year. AF was documented in 142 (21%) of 686 patients. AF was not a significant predictor of 30-day (adjusted odds ratio, 1.01; 95% CI 0.67-1.54; P=0.95) and 1-year (adjusted odds ratio, 0.80; 95% CI, 0.52-1.22; P=0.30) all-cause mortality. Patients with AF already on admission showed higher all-cause mortality at 30 days (52 of 90, 58% versus 19 of 52, 37%; P=0.02) and 1 year (57 of 90, 63% versus 20 of 52, 39%; P=0.004) compared with patients with newly detected AF during hospital stay. AF was associated with a longer time to hemodynamic stabilization (4, interquartile range, 1-8 days versus 3, interquartile range, 1-6 days; P=0.04) at 30 days. Conclusions In cardiogenic shock complicating acute myocardial infarction, all-cause mortality is similar in patients with and without AF. Adverse outcome was detected in the subgroup of patients showing AF already on hospital admission. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01927549.

18.
Eur Heart J ; 40(24): 1903-1906, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226211
19.
Eur Heart J ; 40(24): 1942-1951, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226213

RESUMO

AIMS: The value of platelet function testing (PFT) in predicting clinical outcomes and guiding P2Y12-inhibitor treatment is uncertain. In a pre-specified sub-study of the TROPICAL-ACS trial, we assessed ischaemic and bleeding risks according to high platelet reactivity (HPR) and low platelet reactivity (LPR) to ADP in patients receiving uniform prasugrel vs. PFT-guided clopidogrel or prasugrel. METHODS AND RESULTS: Acute coronary syndrome patients with PFT done 14 days after hospital discharge were included with prior randomization to uniform prasugrel for 12 months (control group, no treatment modification) vs. early de-escalation from prasugrel to clopidogrel and PFT-guided maintenance treatment (HPR: switch-back to prasugrel, non-HPR: clopidogrel). The composite ischaemic endpoint included cardiovascular death, myocardial infarction, or stroke, while key safety outcome was Bleeding Academic Research Consortium (BARC) 2-5 bleeding, from PFT until 12 months. We identified 2527 patients with PFT results available: 1266 were randomized to the guided and 1261 to the control group. Before treatment adjustment, HPR was more prevalent in the guided group (40% vs. 15%), while LPR was more common in control patients (27% vs. 11%). Compared to control patients without HPR on prasugrel (n = 1073), similar outcomes were observed in guided patients kept on clopidogrel [n = 755, hazard ratio (HR): 1.06 (0.57-1.95), P = 0.86] and also in patients with HPR on clopidogrel switched to prasugrel [n = 511, HR: 0.96 (0.47-1.96), P = 0.91]. In contrast, HPR on prasugrel was associated with a higher risk for ischaemic events in control patients [n = 188, HR: 2.16 (1.01-4.65), P = 0.049]. Low platelet reactivity was an independent predictor of bleeding [HR: 1.74 (1.18-2.56), P = 0.005], without interaction (Pint = 0.76) between study groups. CONCLUSION: Based on this substudy of a randomized trial, selecting prasugrel or clopidogrel based on PFT resulted in similar ischaemic outcomes as uniform prasugrel therapy without HPR. Although infrequent, HPR on prasugrel was associated with increased risk of ischaemic events. Low platelet reactivity was a strong and independent predictor of bleeding both on prasugrel and clopidogrel.

20.
Blood ; 134(6): 561-567, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31221672

RESUMO

Membrane-bound plasmin is used by immune cells to degrade extracellular matrices, which facilitates migration. The plasminogen receptor Plg-RKT is expressed by immune cells, including monocytes and macrophages. Among monocytes and macrophages, distinct subsets can be distinguished based on cell surface markers and pathophysiological function. We investigated expression of Plg-RKT by monocyte and macrophage subsets and whether potential differential expression might have functional consequences for cell migration. Proinflammatory CD14++CD16+ human monocytes and Ly6Chigh mouse monocytes expressed the highest levels of Plg-RKT and bound significantly more plasminogen compared with the other respective subsets. Proinflammatory human macrophages, generated by polarization with lipopolysaccharide and interferon-γ, showed significantly higher expression of Plg-RKT compared with alternatively activated macrophages, polarized with interleukin-4 and interleukin-13. Directional migration of proinflammatory monocytes was plasmin dependent and was abolished by anti-Plg-RKT monoclonal antibody, ε-amino-caproic acid, aprotinin, and the aminoterminal fragment of urokinase-type plasminogen activator. In an in vivo peritonitis model, significantly less Ly6Chigh monocyte recruitment was observed in Plg-RKT -/- compared with Plg-RKT +/+ mice. Immunohistochemical analysis of human carotid plaques and adipose tissue showed that proinflammatory macrophages also exhibited high levels of Plg-RKT in vivo. Our data demonstrate higher expression of Plg-RKT on proinflammatory monocyte and macrophage subsets that impacts their migratory capacity.

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