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1.
Int J Cardiol ; 302: 53-58, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31932116

RESUMO

BACKGROUND: Variation in patient characteristics and practice patterns may influence outcomes at a regional level. METHODS: We assessed differences in demographics, practice patterns, outcomes, and the effect of apixaban compared with warfarin in ARISTOTLE (n = 18,201) by prespecified regions: North America, Latin America, Europe, and Asia Pacific. The primary outcomes were stroke/systemic embolism and major bleeding. RESULTS: Compared with other regions, patients from Asia Pacific were younger, more women were enrolled in Latin America. Coronary artery disease was more prevalent in Europe and Asia Pacific had the highest rate of prior stroke and renal impairment. Over 50% of patients in North America were taking ≥9 drugs at randomization, compared with 10% in Latin America. North America had the highest rates of temporary study drug discontinuation and procedures. Time in therapeutic range (INR 2.0-3.0) on warfarin was highest in North America and lowest in Asia Pacific. After adjustment and compared with Europe, patients in Asia Pacific had 2-fold higher risk of stroke/systemic embolism and 3-fold higher risk of intracranial hemorrhage. Patients in Latin America had 2-fold increased risk of all-cause death compared with Europe. The benefits of apixaban compared with warfarin were consistent across regions; there was a pronounced reduction in major bleeding in patients from Asia Pacific compared with other regions (p-interaction = 0.03). CONCLUSIONS: Patients with AF enrolled in prespecified regions in ARISTOTLE had differences in clinical baseline characteristics and practice patterns. After adjustment, patients in Asia Pacific and Latin America had worse outcomes than patients from other regions. The relative benefits of apixaban compared with warfarin were consistent across regions with an even greater treatment effect in the reduction of bleeding in patients from Asia Pacific.

2.
Eur Heart J ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31995195

RESUMO

AIMS: As health systems around the world increasingly look to measure and improve the value of care that they provide to patients, being able to measure the outcomes that matter most to patients is vital. To support the shift towards value-based health care in atrial fibrillation (AF), the International Consortium for Health Outcomes Measurement (ICHOM) assembled an international Working Group (WG) of 30 volunteers, including health professionals and patient representatives to develop a standardized minimum set of outcomes for benchmarking care delivery in clinical settings. METHODS AND RESULTS: Using an online-modified Delphi process, outcomes important to patients and health professionals were selected and categorized into (i) long-term consequences of disease outcomes, (ii) complications of treatment outcomes, and (iii) patient-reported outcomes. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, comorbidities, cognitive function, date of diagnosis, disease duration, medications prescribed and AF procedures, as well as smoking, body mass index (BMI), alcohol intake, and physical activity. Where appropriate, and for ease of implementation, standardization of outcomes and case-mix variables was achieved using ICD codes. The standard set underwent an open review process in which over 80% of patients surveyed agreed with the outcomes captured by the standard set. CONCLUSION: Implementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of chronic AF care. Their consistent definition and collection, using ICD codes where applicable, could also broaden the implementation of more patient-centric clinical outcomes research in AF.

3.
Heart Vessels ; 35(2): 170-176, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31446462

RESUMO

Aspirin should be used for the prevention of cardiovascular (CV) events by the risk-benefit balance. This study was conducted to clarify CV and bleeding events in Japanese aspirin users with a history of CV diseases. This study was a prospective, nationwide, multicenter cooperative registry of Japanese patients with CV diseases at risk of thromboembolism who were taking aspirin (75-325 mg) for at least 1 year. We observed major CV and bleeding events during follow-up. Patients with history of ischemic stroke (IS), transient ischemic attack (TIA), coronary artery disease (CAD), atrial fibrillation (AF), and venous thromboembolism (VTE) were included and analyzed in this sutdy. CV events included IS, TIA, CAD, CV death, angioplasty or stenting, and hospitalization because of CV disease. Bleeding events included major bleeding requiring hospitalization and/or blood transfusion. A total of 1506 patients were categorized into IS/TIA (N = 540), CAD (N = 632), and AF/VTE (N = 232). Among them, 101 patients had two or more categories. CV and bleeding events occurred in 61 (3.82%/year) and 15 patients (0.93%/year), respectively. The annual rates of CV and bleeding events were 2.81% and 0.93% in IS/TIA, 5.32% and 0.75% in CAD, 1.15% and 1.15% in AF/VTE, and 6.44% and 0.91% in two or more disease categories, respectively. The Management of Aspirin-induced Gastrointestinal Complications (MAGIC) study clarified the rates of major CV and bleeding events with long-term use of aspirin in patients with prior CV diseases in real-world clinical practice. The risk-benefit balance of aspirin was acceptable in patients with IS/TIA, CAD, and multiple CV diseases but not in those with AF/VTE.Trial Registration: The MAGIC Study is registered at UMIN Clinical Trial Registry (www.umin.ac.jp/ctr/index-j.htm), number UMIN000000750.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31821482

RESUMO

BACKGROUND: Most clinical risk stratification models are based on measurement at a single time-point rather than serial measurements. Artificial intelligence (AI) is able to predict one-dimensional outcomes from multi-dimensional datasets. Using data from GARFIELD-AF registry, a new AI model was developed for predicting clinical outcomes in atrial fibrillation (AF) patients up to 1 year based on sequential measures of PT-INR within 30 days of enrolment. METHODS AND RESULTS: Patients with newly diagnosed AF who were treated with vitamin K antagonists (VKA) and had at least 3 measurements of PT-INR taken over the first 30 days after prescription were analyzed. The AI model was constructed with multilayer neural network including long short-term memory (LSTM) and one-dimensional convolution layers. The neural network was trained using PT-INR measurements within days 0-30 after starting treatment and clinical outcomes over days 31-365 in a derivation cohort (cohorts 1-3; n = 3185). Accuracy of the AI model at predicting major bleed, stroke/SE, and death was assessed in a validation cohort (cohorts 4-5; n = 1523). The model's c-statistic for predicting major bleed, stroke/SE, and all-cause death was 0.75, 0.70, and 0.61, respectively. CONCLUSIONS: Using serial PT-INR values collected within 1 month after starting VKA, the new AI model performed better than time in therapeutic range (TTR) at predicting clinical outcomes occurring up to 12 months thereafter. Serial PT-INR values contain important information that can be analyzed by computer to help predict adverse clinical outcomes.

5.
Int J Stroke ; : 1747493019891516, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847794

RESUMO

BACKGROUND: It is not always possible to verify whether a patient complaining of symptoms consistent with transient ischemic attack has had an actual cerebrovascular event. RESEARCH QUESTION: To characterize the risk of cardiovascular events associated with a history of stroke/transient ischemic attack in patients with atrial fibrillation. STUDY DESIGN AND METHODS: This study investigated the clinical characteristics and outcomes of patients with a history of stroke/transient ischemic attack among 52,014 patients enrolled prospectively in GARFIELD-AF registry. The diagnosis of stroke or transient ischemic attack was not protocol defined but based on physicians' assessment. Patients' one-year risk of death, stroke/systemic embolism, and major bleeding was assessed by multivariable Cox regression. RESULTS: At enrollment, 5617 (10.9%) patients were reported to have a history of stroke or transient ischemic attack. Patients with stroke or transient ischemic attack were older and had a greater burden of diabetes, moderate-to-severe kidney disease, and atherothrombosis and higher median CHA2DS2-VASc and HAS-BLED scores than those without history of stroke or transient ischemic attack. After adjustment, prior stroke/transient ischemic attack was associated with significantly higher risk for all-cause mortality (hazard ratio (HR), 1.26; 95% confidence interval (CI), 1.12-1.42), cardiovascular death (HR, 1.22; 95% CI, 1.01-1.48), non-cardiovascular death (HR, 1.39; 95% CI, 1.15-1.68), and stroke/systemic embolism (HR, 2.17; 95% CI, 1.80-2.63) than patients without history of stroke/transient ischemic attack. In patients with a prior stroke alone higher risk was observed for all-cause mortality (HR, 1.29; 95% CI, 1.11-1.50), non-cardiovascular death (HR, 1.39; 95% CI, 1.10-1.77), and stroke/systemic embolism (HR, 2.29; 95% CI, 1.83-2.86). No significantly elevated risk of adverse events was seen for patients with history of transient ischemic attack alone. INTERPRETATION: A history of prior stroke or transient ischemic attack is a strong independent risk factor for mortality and stroke/systemic embolism. This excess risk is mainly attributed to a history of stroke (with or without transient ischemic attack), whereas history of transient ischemic attack is a weaker predictor. Clinical trial registration: NCT01090362.

6.
Circulation ; 140(22): 1834-1850, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31765261

RESUMO

Cardiac thromboembolism attributed to atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes. Stroke may be the first manifestation of previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic strokes, strategies of searching for AF after a stroke using ECG monitoring followed by oral anticoagulation (OAC) treatment have been proposed to prevent recurrent cardioembolic strokes. This white paper by experts from the AF-SCREEN International Collaboration summarizes existing evidence and knowledge gaps on searching for AF after a stroke by using ECG monitoring. New AF can be detected by routine plus intensive ECG monitoring in approximately one-quarter of patients with ischemic stroke. It may be causal, a bystander, or neurogenically induced by the stroke. AF after a stroke is a risk factor for thromboembolism and a strong marker for atrial myopathy. After acute ischemic stroke, patients should undergo 72 hours of electrocardiographic monitoring to detect AF. The diagnosis requires an ECG of sufficient quality for confirmation by a health professional with ECG rhythm expertise. AF detection rate is a function of monitoring duration and quality of analysis, AF episode definition, interval from stroke to monitoring commencement, and patient characteristics including old age, certain ECG alterations, and stroke type. Markers of atrial myopathy (eg, imaging, atrial ectopy, natriuretic peptides) may increase AF yield from monitoring and could be used to guide patient selection for more intensive/prolonged poststroke ECG monitoring. Atrial myopathy without detected AF is not currently sufficient to initiate OAC. The concept of embolic stroke of unknown source is not proven to identify patients who have had a stroke benefitting from empiric OAC treatment. However, some embolic stroke of unknown source subgroups (eg, advanced age, atrial enlargement) might benefit more from non-vitamin K-dependent OAC therapy than aspirin. Fulfilling embolic stroke of unknown source criteria is an indication neither for empiric non-vitamin K-dependent OAC treatment nor for withholding prolonged ECG monitoring for AF. Clinically diagnosed AF after a stroke or a transient ischemic attack is associated with significantly increased risk of recurrent stroke or systemic embolism, in particular, with additional stroke risk factors, and requires OAC rather than antiplatelet therapy. The minimum subclinical AF duration required on ECG monitoring poststroke/transient ischemic attack to recommend OAC therapy is debated.

7.
Europace ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747004

RESUMO

AIMS: Guidelines do not recommend to take pattern of atrial fibrillation (AF) into account for the indication of anticoagulation (AC). We assessed AF pattern and the risk of cardiovascular events during 2-years of follow-up. METHODS AND RESULTS: We categorized AF as paroxysmal, persistent, or permanent in 29 181 patients enrolled (2010-15) in the Global Anticoagulant Registry In the FIELD of AF (GARFIELD-AF). We used multivariable Cox regression to assess the risks of stroke/systemic embolism (SE) and death across patterns of AF, and whether this changed with AC on outcomes. Atrial fibrillation pattern was paroxysmal in 14 344 (49.2%), persistent in 8064 (27.6%), and permanent 6773 (23.2%) patients. Median CHA2DS2-VASc, GARFIELD-AF, and HAS-BLED scores assessing the risk of stroke/SE and/or bleeding were similar across AF patterns, but the risk of death, as assessed by the GARFIELD-AF risk calculator, was higher in non-paroxysmal than in paroxysmal AF patterns. During 2-year follow-up, after adjustment, non-paroxysmal AF patterns were associated with significantly higher rates of all-cause death, stroke/SE, and new/worsening congestive heart failure (CHF) than paroxysmal AF in non-anticoagulated patients only. In anticoagulated patients, a significantly higher risk of death but not of stroke/SE and new/worsening CHF persisted in non-paroxysmal compared with paroxysmal AF patterns. CONCLUSION: In non-anticoagulated patients, non-paroxysmal AF patterns were associated with higher risks of stroke/SE, new/worsening HF and death than paroxysmal AF. In anticoagulated patients, the risk of stroke/SE and new/worsening HF was similar across all AF patterns. Thus AF pattern is no longer prognostic for stroke/SE when patients are treated with anticoagulants. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.

8.
Thromb Res ; 184: 129-135, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31739151

RESUMO

INTRODUCTION: Binding of platelet glycoprotein (GP)Ibα with von-Willebrand factor (VWF) exclusively mediates the initial platelet adhesion to injured vessel wall. To understand the mechanism of biomedical functions, we calculated the dynamic fluctuating three-dimensional (3D) structures and dissociation energy for GPIbα with various single amino-acid substitution at G233, which location is known to cause significant changes in platelet adhesive characteristics. MATERIAL AND METHODS: Molecular dynamics (MD) simulation was utilized to calculate 3D structures and Potential of Mean Force (PMF) for wild-type VWF bound with wild-type, G233A (equal function), G233V (gain of function), and G233D (loss of function) GPIbα. Simulation was done on water-soluble condition with time-step of 2 × 10-15 s using NAnoscale Molecular Dynamics (NAMD) with Chemistry at HARvard Molecular Mechanics (CHARMM) force field. Initial structure for each mutant was obtained by inducing single amino-acid substitution to the stable water-soluble binding structure of wild-type. RESULTS: The most stable structures of wild-type VWF bound to GPIbα in wild-type or any mutant did not differ. However, bond dissociation energy defined as difference of PMF between most stable structure and the structure at 65 Šmass center distances in G233D was 4.32 kcal/mol (19.5%) lower than that of wild-type. Approximately, 2.07 kcal/mol energy was required to dissociate VWF from GPIbα with G233V at mass center distance from 48 to 52 Å, which may explain the apparent "gain of function" in G233V. CONCLUSION: The mechanism of substantially different biochemical characteristics of GPIbα with mutations in G233 location was predicted from physical movement of atoms constructing these proteins.

9.
Circulation ; 140(23): 1878-1880, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31553202
10.
Lancet ; 394(10204): 1169-1180, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31484629

RESUMO

BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8-3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74-0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, pinteraction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78-1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75-1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48-2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36-3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74-1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75-0·95, p=0·005, in contrast to patients without PCI where it did not, pinteraction=0·012. Benefit was present irrespective of time from most recent PCI. INTERPRETATION: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk. FUNDING: AstraZeneca.


Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Aspirina/uso terapêutico , Doenças Cardiovasculares/mortalidade , Angiografia Coronária , Ponte de Artéria Coronária , Doença da Artéria Coronariana/complicações , Estenose Coronária/diagnóstico por imagem , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hemorragia/induzido quimicamente , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Intervenção Coronária Percutânea , Prevenção Secundária , Acidente Vascular Cerebral/epidemiologia
11.
Thromb Haemost ; 19(10): 1675-1685, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31370075

RESUMO

Isolated distal deep vein thrombosis (IDDVT) represents up to half of all lower limb DVT. This study investigated treatment patterns and outcomes in 2,145 patients with IDDVT in comparison with those with proximal DVT (PDVT; n = 3,846) and pulmonary embolism (PE; n = 4,097) enrolled in the GARFIELD-VTE registry. IDDVT patients were more likely to have recently undergone surgery (14.6%) or experienced leg trauma (13.2%) than PDVT patients (11.0 and 8.7%, respectively) and PE patients (12.7 and 4.5%, respectively). Compared with IDDVT, patients with PDVT or PE were more likely to have active cancer (7.2% vs. 9.9% and 10.3%). However, influence of provoking factors on risk of recurrence in IDDVT remains controversial. Nearly all patients (IDDVT, PDVT, and PE) were given anticoagulant therapy. In IDDVT, PDVT, and PE groups the proportion of patients receiving anticoagulant therapy was 61.4, 73.9, and 81.1% at 6 months and 45.8, 54.7, and 61.9% at 12 months. Over 12 months, the incidence of all-cause mortality, cancer, and recurrence was significantly lower in IDDVT patients than PDVT patients (hazard ratio [HR], 0.61 [95% confidence interval [CI], 0.48-0.77]; sub-HR [sHR], 0.60 [95% CI, 0.39-0.93]; and sHR, 0.76 [95% CI, 0.60-0.97]). Likewise, risk of death and incident cancer was significantly (both p < 0.05) lower in patients with IDDVT compared with PE. This study reveals a global trend that most IDDVT patients as well as those with PDVT and PE are given anticoagulant therapy, in many cases for at least 12 months.

12.
J Immunol ; 203(5): 1313-1324, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31366713

RESUMO

Bovine leukemia virus (BLV) infection is a chronic viral infection of cattle and endemic in many countries, including Japan. Our previous study demonstrated that PGE2, a product of cyclooxygenase (COX) 2, suppresses Th1 responses in cattle and contributes to the progression of Johne disease, a chronic bacterial infection in cattle. However, little information is available on the association of PGE2 with chronic viral infection. Thus, we analyzed the changes in plasma PGE2 concentration during BLV infection and its effects on proviral load, viral gene transcription, Th1 responses, and disease progression. Both COX2 expression by PBMCs and plasma PGE2 concentration were higher in the infected cattle compared with uninfected cattle, and plasma PGE2 concentration was positively correlated with the proviral load. BLV Ag exposure also directly enhanced PGE2 production by PBMCs. Transcription of BLV genes was activated via PGE2 receptors EP2 and EP4, further suggesting that PGE2 contributes to disease progression. In contrast, inhibition of PGE2 production using a COX-2 inhibitor activated BLV-specific Th1 responses in vitro, as evidenced by enhanced T cell proliferation and Th1 cytokine production, and reduced BLV proviral load in vivo. Combined treatment with the COX-2 inhibitor meloxicam and anti-programmed death-ligand 1 Ab significantly reduced the BLV proviral load, suggesting a potential as a novel control method against BLV infection. Further studies using a larger number of animals are required to support the efficacy of this treatment for clinical application.

13.
Am J Med ; 132(12): 1431-1440.e7, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31306621

RESUMO

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes. METHODS: Adults with newly diagnosed atrial fibrillation and ≥1 investigator-defined stroke risk factor were enrolled in GARFIELD-AF between March 2010 and September 2015. The association between prior acute coronary syndromes and long-term outcomes was determined using a Cox proportional hazards model, adjusting for baseline risk factors, oral anticoagulation (OAC) ± antiplatelet (AP) therapy, and usual care. RESULTS: Of 39,679 patients, 10.5% had a history of acute coronary syndromes. At 2-year follow-up, patients with prior acute coronary syndromes had higher adjusted risks of stroke/systemic embolism (hazard ratio [HR] 1.39; 95% confidence interval [CI], 1.08-1.78), major bleeding (HR 1.30; 95% CI, 0.95 -1.79), all-cause mortality (HR 1.34; 95% CI, 1.21 -1.49), cardiovascular mortality (HR 1.85; 95% CI, 1.51-2.26), and new acute coronary syndromes (HR 3.42; 95% CI, 2.62-4.45). Comparing antithrombotic therapy in the acute coronary syndromes vs no acute coronary syndromes groups, most patients received OAC ± AP: 60.8% vs 66.1%, but AP therapy was more likely in the acute coronary syndromes group (68.1% vs 32.9%), either alone (34.9% vs 20.8%) or with OAC (33.2% vs 12.1%). Overall, 17.8% in the acute coronary syndromes group received dual AP therapy with (5.3%) or without OAC (12.5%). Among patients with moderate/high risk for stroke/systemic embolism, fewer in the acute coronary syndromes group received OAC with or without AP therapy (Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, prior Stroke, TIA, or thromboembolism, Vascular disease, Age 65-74 years, Sex category [CHA2DS2-VASc] 2: 52.1% vs 64.6%; CHA2DS2-VASc ≥3: 62.0% vs 70.7%), and the majority with a Hypertension (uncontrolled systolic blood pressure >160 mm Hg), Abnormal renal or liver function, previous Stroke, Bleeding history or predisposition, Labile international normalized ratios, Elderly, and concomitant Drugs or alcohol excess (HAS-BLED) score ≥3 were on AP therapy (83.8% vs 65.5%). CONCLUSIONS: In GARFIELD-AF, previous acute coronary syndromes are associated with worse 2-year outcomes and a greater likelihood of under-treatment with OAC, while two-thirds of patients receive AP therapy. Major bleeding was more common with previous acute coronary syndromes, even after adjusting for all risk factors.

14.
Nat Rev Dis Primers ; 5(1): 39, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171787

RESUMO

ST-segment elevation myocardial infarction (STEMI) is the most acute manifestation of coronary artery disease and is associated with great morbidity and mortality. A complete thrombotic occlusion developing from an atherosclerotic plaque in an epicardial coronary vessel is the cause of STEMI in the majority of cases. Early diagnosis and immediate reperfusion are the most effective ways to limit myocardial ischaemia and infarct size and thereby reduce the risk of post-STEMI complications and heart failure. Primary percutaneous coronary intervention (PCI) has become the preferred reperfusion strategy in patients with STEMI; if PCI cannot be performed within 120 minutes of STEMI diagnosis, fibrinolysis therapy should be administered to dissolve the occluding thrombus. The initiation of networks to provide around-the-clock cardiac catheterization availability and the generation of standard operating procedures within hospital systems have helped to reduce the time to reperfusion therapy. Together with new advances in antithrombotic therapy and preventive measures, these developments have resulted in a decrease in mortality from STEMI. However, a substantial amount of patients still experience recurrent cardiovascular events after STEMI. New insights have been gained regarding the pathophysiology of STEMI and feed into the development of new treatment strategies.


Assuntos
Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Biomarcadores/análise , Biomarcadores/sangue , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/fisiopatologia , Ecocardiografia/métodos , Eletrocardiografia/métodos , Humanos , Programas de Rastreamento/métodos , Intervenção Coronária Percutânea/métodos , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Resultado do Tratamento , Troponina I/análise , Troponina I/sangue
15.
Thromb Haemost ; 119(8): 1365-1372, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31183844

RESUMO

Upper extremity deep vein thrombosis (UEDVT) is less common than lower extremity DVT (LEDVT) and consequently less well characterized. This study compared clinical characteristics and 1-year outcomes between 438 UEDVT patients and 7,602 LEDVT patients recruited in the GARFIELD-VTE registry. UEDVT patients were significantly more likely to have a central venous catheter than those with LEDVT (11.5% vs. 0.5%; p < 0.0001), and had a higher rate of active cancer (16.2%) or recent hospitalization (19.4%) compared with LEDVT patients (8.7% and 11.2%, respectively). Nearly all patients with UEDVT and LEDVT were initiated on anticoagulant therapy, which was a direct oral anticoagulant in one-third individuals in both groups. At 3, 6, and 12 months, the proportion of UEDVT and LEDVT patients who were receiving anticoagulant therapy was 82.6 and 87.4%, 66.0 and 72.6%, and 45.7 and 54.6%, respectively. In the UEDVT and LEDVT groups, VTE recurrence rate was 4.0 (95% confidence interval [CI], 2.4-6.7) and 5.5 (95% CI, 4.9-6.1) per 100 person-years, respectively; major bleed was noted in 1.3 (95% CI, 0.6-3.2) and 1.6 (95% CI, 1.3-1.9) per 100 person-years and all-cause mortality in 9.7 (95% CI, 7.1-13.4) and 6.7 (95% CI, 6.1-7.3) per 100 person-years, respectively. Hence, risk of recurrence was similar in the two groups whereas all-cause mortality was significantly higher in the UEDVT group than the LEDVT group (p = 0.0338). This latter finding was likely due to the high prevalence of cancer in the UEDVT group.

16.
J Thromb Haemost ; 17(10): 1694-1706, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31220403

RESUMO

BACKGROUND: Parenteral anticoagulants and vitamin K antagonists (VKAs) have constituted the cornerstone of venous thromboembolism (VTE) treatment. Meanwhile, direct oral anticoagulants (DOACs) provide physicians with an alternative. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE observes real-world treatment practices. OBJECTIVES: Describe initial anticoagulation (AC) treatment patterns in VTE patients who received parenteral AC, VKAs, and/or DOACs within ±30 days of diagnosis. METHODS: VTE patients were categorized into parenteral AC only, parenteral AC with transition to VKA, VKA only, parenteral AC with transition to DOAC, and DOAC only. RESULTS: A total of 9647 patients were initiated on AC treatment alone. 4781 (49.6%) patients received DOACs ± parenteral ACs; 3187 (33.0%), VKA ± parenteral ACs; and 1679 (17.4%) parenteral ACs alone. Rivaroxaban was the most frequently used DOAC (79.4%). DOACs were more frequently used in North America/Australia (58.1%), Europe (52.2%), and Asia (47.6%) than in Latin America (29.7%) and the Middle East/South Africa (32.5%). In patients with suspected VTE, most received parenteral AC monotherapy (67.7%). Patients with deep vein thrombosis were more likely to receive DOACs alone than those with pulmonary embolism with or without deep vein thrombosis (36.2% vs 25.9%). Active cancer patients received parenteral AC alone (58.9%), with 25.5% receiving DOAC ± parenteral AC and 12.8% parenteral AC and VKA. A total of 46.5% of pregnant patients received parenteral AC monotherapy, 34.0% were treated with VKA ± parenteral AC, and 19.5% received a DOAC (± parenteral AC). CONCLUSION: AC treatment patterns vary by patient population, geographic region and site of VTE. Guidelines for AC therapy are not always adhered to.

17.
Thromb Res ; 179: 121-127, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129447

RESUMO

INTRODUCTION: Thrombin inhibitor and anti-Xa are now widely used in clinical practice. However, the difference between thrombin inhibitor and anti-Xa in prevention of thrombosis is still to be elucidated. MATERIALS AND METHODS: Computer simulator implementing the function of platelet, coagulation, fibrinolysis and blood flow was developed. The function of thrombin is defined as to activated platelet at the rate of 0.01 s-1 and to produce fibrin at the rate of 0.1 s-1 in control. The effect of thrombin inhibitor was settled to reduce the rate of platelet activation and fibrin generation changed from 10 to 100% as compared to the control. The local thrombin generation rate on activated platelet was settled as 1.0 s-1 as a control. The effect of anti-Xa was settled to reduce to thrombin generation rate on activated platelet from 10% to 100% as compared to the control. The sizes of thrombi formed at site of endothelial injury in the presence and absence of thrombin inhibitor and anti-Xa were compared. RESULTS AND CONCLUSIONS: The size of thrombi formed by 30-s perfusion of blood at site of endothelial injury reduced both in the presence of thrombin inhibitor and anti-Xa. There was significant positive relationship between thrombin inhibitor effect and the size of formed thrombi with R value of 0.96. (p < 0.0001) However, the sizes of thrombi were not influence by anti-Xa until it decreased 30% or less as compared to control. There was no significant relationship between anti-Xa effect and the size of formed thrombi. (R = 0.39, p = 0.09) Our results suggest the different dose-dependent effects of thrombin inhibitor and anti-Xa on thrombus formation at least in specific conditions. Computer simulation may help to predict quantitative antithrombotic effects of various antithrombotic agents.

18.
JAMA Cardiol ; 4(6): 526-548, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31066873

RESUMO

Importance: Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes. Objective: To assess the treatment strategies and 1-year clinical outcomes of antithrombotic and CHF therapies for patients with newly diagnosed AF with concomitant CHF stratified by etiology (ischemic cardiomyopathy [ICM] vs nonischemic cardiomyopathy [NICM]). Design, Setting, and Participants: The GARFIELD-AF registry is a prospective, noninterventional registry. A total of 52 014 patients with AF were enrolled between March 2010 and August 2016. A total of 11 738 patients 18 years and older with newly diagnosed AF (≤6 weeks' duration) and at least 1 investigator-determined stroke risk factor were included. Data were analyzed from December 2017 to September 2018. Exposures: One-year follow-up rates of death, stroke/systemic embolism, and major bleeding were assessed. Main Outcomes and Measures: Event rates per 100 person-years were estimated from the Poisson model and Cox hazard ratios (HRs) and 95% confidence intervals. Results: The median age of the population was 71.0 years, 22 987 of 52 013 were women (44.2%) and 31 958 of 52 014 were white (61.4%). Of 11 738 patients with CHF, 4717 (40.2%) had ICM and 7021 (59.8%) had NICM. Prescription of oral anticoagulant and antiplatelet drugs was not balanced between groups. Oral anticoagulants with or without antiplatelet drugs were used in 2753 patients with ICM (60.1%) and 5082 patients with NICM (73.7%). Antiplatelets were prescribed alone in 1576 patients with ICM (34.4%) and 1071 patients with NICM (15.5%). Compared with patients with NICM, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (72.6% [3439] vs 60.3% [4236]) and of ß blockers (63.3% [2988] vs 53.2% [3737]) was higher in patients with ICM. Rates of all-cause and cardiovascular death per 100 patient-years were significantly higher in the ICM group (all-cause death: ICM, 10.2; 95% CI, 9.2-11.1; NICM, 7.0; 95% CI, 6.4-7.6; cardiovascular death: ICM, 5.1; 95% CI, 4.5-5.9; NICM, 2.9; 95% CI, 2.5-3.4). Stroke/systemic embolism rates tended to be higher in ICM groups compared with NICM groups (ICM, 2.0; 95% CI, 1.6-2.5; NICM, 1.5; 95% CI, 1.3-1.9). Major bleeding rates were significantly higher in the ICM group (1.1; 95% CI, 0.8-1.4) compared with the NICM group (0.7; 95% CI, 0.5-0.9). Conclusions and Relevance: Patients with ICM received oral anticoagulants with or without antiplatelet drugs less frequently and antiplatelets alone more frequently than patients with NICM, but they received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers more often than patients with NICM. All-cause and cardiovascular death rates were higher in patients with ICM than patients with NICM. Trial Registration: ClinicalTrials.gov Identifier: NCT01090362.

20.
Circulation ; 139(22): 2528-2536, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-30882238

RESUMO

BACKGROUND: In DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the composite end point of cardiovascular death/hospitalization for heart failure (HHF) in a broad population of patients with type 2 diabetes mellitus. However, the impact of baseline left ventricular ejection fraction (EF) on the clinical benefit of sodium-glucose cotransporter 2 inhibition is unknown. METHODS: In the DECLARE-TIMI 58 trial, baseline heart failure (HF) status was collected from all patients, and EF was collected when available. HF with reduced EF (HFrEF) was defined as EF <45%. Outcomes of interest were the composite of cardiovascular death/HHF, its components, and all-cause mortality. RESULTS: Of 17 160 patients, 671 (3.9%) had HFrEF, 1316 (7.7%) had HF without known reduced EF, and 15 173 (88.4%) had no history of HF at baseline. Dapagliflozin reduced cardiovascular death/HHF more in patients with HFrEF (hazard ratio [HR], 0.62 [95% CI, 0.45-0.86]) than in those without HFrEF (HR, 0.88 [95% CI, 0.76-1.02]; P for interaction=0.046), in whom the treatment effect of dapagliflozin was similar in those with HF without known reduced EF (HR, 0.88 [95% CI, 0.66-1.17]) and those without HF (HR, 0.88 [95% CI, 0.74-1.03]). Whereas dapagliflozin reduced HHF both in those with (HR, 0.64 [95% CI, 0.43-0.95]) and in those without HFrEF (HR, 0.76 [95% CI, 0.62-0.92]), it reduced cardiovascular death only in patients with HFrEF (HR, 0.55 [95% CI, 0.34-0.90]) but not in those without HFrEF (HR, 1.08 [95% CI, 0.89-1.31]; P for interaction=0.012). Likewise, dapagliflozin reduced all-cause mortality in patients with HFrEF (HR, 0.59 [95% CI, 0.40-0.88;) but not in those without HFrEF (HR, 0.97 [95% CI, 0.86-1.10]; P for interaction=0.016). CONCLUSIONS: In the first sodium-glucose cotransporter 2 inhibitor cardiovascular outcome trial to evaluate patients with type 2 diabetes mellitus stratified by EF, we found that dapagliflozin reduced HHF in patients with and without HFrEF and reduced cardiovascular death and all-cause mortality in patients with HFrEF. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01730534.

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