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BACKGROUND: Oral anticoagulants (OAC) are underutilized in older patients with atrial fibrillation, despite proven clinical benefits. Our objective was to investigate baseline characteristics, treatment patterns, and impact of anticoagulation upon clinical outcomes with respect to age. METHODS: Adults with newly diagnosed atrial fibrillation were recruited into the prospective observational registry, GARFIELD-AF, and followed up for 24 months. Adjusted hazard ratios (HR) were obtained via Cox proportional-hazards models with applied weights, to quantify the association of age with clinical outcomes. Comparative effectiveness of OAC vs No OAC and non-vitamin K oral anticoagulants (NOAC) vs vitamin K antagonists (VKA) were assessed using a propensity score with an overlap weighting scheme. RESULTS: Of 52,018 patients, 32.6% were 65-74 years of age, 29.3% were 75-84 years, and 7.9% were ≥85 years. OAC treatment was associated with a numerical reduction in all-cause mortality among those aged 65-74 years (HR; 95% confidence interval) (0.86; 0.69-1.06) and aged 75-84 years (0.89; 0.75-1.05) and a significant reduction in patients ≥85 years (0.77; 0.63-0.95) vs no OAC. Similarly, OACs were associated with a decrease in stroke: 65-74 (0.51; 0.35-0.76) and ≥85 years (0.58; 0.34-0.99) and a numerical decrease in 75-84 years (0.84; 0.59-1.18). No increase in major bleeding was observed in patients aged ≥85 treated with OACs. Compared with VKA, NOACs were associated with a significant reduction in all-cause mortality in patients aged <65 and 65-74, with numerical reductions in those aged 75-84 and ≥85 years. CONCLUSIONS: Older patients using OACs saw lower all-cause mortality and stroke risk; NOACs had less mortality and major bleeding compared with VKAs.
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Fibrilação Atrial , Acidente Vascular Cerebral , Adulto , Humanos , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/induzido quimicamente , Anticoagulantes , Administração Oral , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Hemorragia/complicações , Sistema de Registros , Fatores de RiscoRESUMO
Brain perfusion is sensitive to changes in CO2 levels (CO2 reactivity). Previously, we showed a pathological cerebral blood flow (CBF) reduction in the majority of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients during orthostatic stress. Limited data are available on the relation between CO2 and CBF changes in ME/CFS patients. Therefore, we studied this relation between ME/CFS patients and healthy controls (HC) during tilt testing. In this retrospective study, supine and end-tilt CBF, as measured by extracranial Doppler flow, were compared with PET CO2 data in female patients either with a normal heart rate and blood pressure (HR/BP) response or with postural orthostatic tachycardia syndrome (POTS), and in HC. Five hundred thirty-five female ME/CFS patients and 34 HC were included. Both in supine position and at end-tilt, there was a significant relation between CBF and PET CO2 in patients (p < 0.0001), without differences between patients with a normal HR/BP response and with POTS. The relations between the %CBF change and the PET CO2 reduction were both significant in patients and HC (p < 0.0001 and p = 0.0012, respectively). In a multiple regression analysis, the patient/HC status and PET CO2 predicted CBF. The contribution of the PET CO2 to CBF changes was limited, with low adjusted R2 values. In female ME/CFS patients, CO2 reactivity, as measured during orthostatic stress testing, is similar to that of HC and is independent of the type of hemodynamic abnormality. However, the influence of CO2 changes on CBF changes is modest in female ME/CFS patients.
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Síndrome de Fadiga Crônica , Síndrome da Taquicardia Postural Ortostática , Humanos , Adulto , Feminino , Dióxido de Carbono , Estudos Retrospectivos , Circulação Cerebrovascular , EncéfaloRESUMO
BACKGROUND: Many patients with atrial fibrillation suffer from comorbid vascular disease. The comparative efficacy and safety of different types of oral anticoagulation (OAC) in this patient group have not been widely studied. METHODS: Adults with newly diagnosed atrial fibrillation were recruited into the prospective observational registry, GARFIELD-AF, and followed for 24 months. Associations of vascular disease with clinical outcomes were analyzed using adjusted hazard ratios (HR) obtained via Cox proportional-hazard modeling. Outcomes of OAC vs no OAC, and of non-vitamin K antagonist OAC (NOAC) vs vitamin K antagonist (VKA) treatment, were compared by overlap propensity-weighted Cox proportional-hazard models. RESULTS: Of 51,574 atrial fibrillation patients, 25.9% had vascular disease. Among eligible atrial fibrillation patients, those with vascular disease received OAC less frequently than those without (63% vs 73%). Over 2-year follow-up, patients with vascular disease showed a higher risk of all-cause mortality (HR 1.30; 95% confidence interval [CI], 1.16-1.47) and cardiovascular mortality (HR 1.59; 95% CI, 1.28-1.97). OAC was associated with a significant decrease in all-cause mortality and non-hemorrhagic stroke, and increased risk of major bleeding in non-vascular disease. In vascular disease, similar but non-significant trends existed for stroke and major bleeding. A significantly lower risk of all-cause mortality (HR 0.74; 95% CI, 0.61-0.90) and major bleeding (HR 0.45; 95% CI, 0.29-0.70) was observed in vascular disease patients treated with NOACs, compared with VKAs. CONCLUSIONS: Atrial fibrillation patients with a history of vascular disease have worse long-term outcomes than those without. The association of NOACs vs VKA with clinical outcomes was more evident in atrial fibrillation patients with vascular disease.
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Fibrilação Atrial , Acidente Vascular Cerebral , Adulto , Humanos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Administração Oral , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Hemorragia/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Sistema de Registros , Fatores de RiscoRESUMO
AIMS: This study aims to describe both management and prognosis of patients with diabetes mellitus (DM) and newly diagnosed atrial fibrillation (AF), overall as well as by antidiabetic treatment, and to assess the influence of oral anticoagulation (OAC) on outcomes by DM status. METHODS: The study population comprised 52 010 newly diagnosed patients with AF, 11 542 DM and 40 468 non-DM, enrolled in the GARFIELD-AF registry. Follow-up was truncated at 2 years after enrolment. Comparative effectiveness of OAC versus no OAC was assessed by DM status using a propensity score overlap weighting scheme and weights were applied to Cox models. RESULTS: Patients with DM [39.3% oral antidiabetic drug (OAD), 13.4% insulin ± OAD, 47.2% on no antidiabetic drug] had higher risk profile, OAC use, and rates of clinical outcomes compared with patients without DM. OAC use was associated in patients without DM and patients with DM with lower risk of all-cause mortality [hazard ratio 0.75 (0.69-0.83), 0.74 (0.64-0.86), respectively] and stroke/systemic embolism (SE) [0.69 (0.58-0.83), 0.70 (0.53-0.93), respectively]. The risk of major bleeding with OAC was similarly increased in patients without DM and those with DM [1.40 (1.14-1.71), 1.37 (0.99-1.89), respectively]. Patients with insulin-requiring DM had a higher risk of all-cause mortality and stroke/SE [1.91 (1.63-2.24)], [1.57 (1.06-2.35), respectively] compared with patients without DM, and experienced significant risk reductions of all-cause mortality and stroke/SE with OAC [0.73 (0.53-0.99); 0.50 (0.26-0.97), respectively]. CONCLUSIONS: In both patients with DM and patients without DM with AF, OAC was associated with lower risk of all-cause mortality and stroke/SE. Patients with insulin-requiring DM derived significant benefit from OAC.
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Fibrilação Atrial , Diabetes Mellitus , Insulinas , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Anticoagulantes/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Sistema de Registros , Administração Oral , Fatores de RiscoRESUMO
Background: Orthostatic intolerance (OI) is a core diagnostic criterion in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The majority of ME/CFS patients have no evidence of hypotension or postural orthostatic tachycardia syndrome (POTS) during head-up tilt, but do show a significantly larger reduction in stroke volume index (SVI) when upright compared to controls. Theoretically a reduction in SVI should be accompanied by a compensatory increase in heart rate (HR). When there is an incomplete compensatory increase in HR, this is considered chronotropic incompetence. This study explored the relationship between HR and SVI to determine whether chronotropic incompetence was present during tilt testing in ME/CFS patients. Methods: From a database of individuals who had undergone tilt testing with Doppler measurements for SVI both supine and end-tilt, we selected ME/CFS patients and healthy controls (HC) who had no evidence of POTS or hypotension during the test. To determine the relation between the HR increase and SVI decrease during the tilt test in patients, we calculated the 95% prediction intervals of this relation in HC. Chronotropic incompetence in patients was defined as a HR increase below the lower limit of the 95th % prediction interval of the HR increase in HC. Results: We compared 362 ME/CFS patients with 52 HC. At end-tilt, tilt lasting for 15 (4) min, ME/CFS patients had a significantly lower SVI (22 (4) vs. 27 (4) ml/m2; p < 0.0001) and a higher HR (87 (11) vs. 78 (15) bpm; p < 0.0001) compared to HC. There was a similar relationship between HR and SVI between ME/CFS patients and HC in the supine position. During tilt ME/CFS patients had a lower HR for a given SVI; 37% had an inadequate HR increase. Chronotropic incompetence was more common in more severely affected ME/CFS patients. Conclusion: These novel findings represent the first description of orthostatic chronotropic incompetence during tilt testing in ME/CFS patients.
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Aims: This study aimed to identify relationships in recently diagnosed atrial fibrillation (AF) patients with respect to anticoagulation status, use of guideline-directed medical therapy (GDMT) for comorbid cardiovascular conditions (co-GDMT), and clinical outcomes. The Global Anticoagulant Registry in the FIELD (GARFIELD)-AF is a prospective, international registry of patients with recently diagnosed non-valvular AF at risk of stroke (NCT01090362). Methods and results: Guideline-directed medical therapy was defined according to the European Society of Cardiology guidelines. This study explored co-GDMT use in patients enrolled in GARFIELD-AF (March 2013-August 2016) with CHA2DS2-VASc ≥ 2 (excluding sex) and ≥1 of five comorbidities-coronary artery disease, diabetes mellitus, heart failure, hypertension, and peripheral vascular disease (n = 23 165). Association between co-GDMT and outcome events was evaluated with Cox proportional hazards models, with stratification by all possible combinations of the five comorbidities. Most patients (73.8%) received oral anticoagulants (OACs) as recommended; 15.0% received no recommended co-GDMT, 40.4% received some, and 44.5% received all co-GDMT. At 2 years, comprehensive co-GDMT was associated with a lower risk of all-cause mortality [hazard ratio (HR) 0.89 (0.81-0.99)] and non-cardiovascular mortality [HR 0.85 (0.73-0.99)] compared with inadequate/no GDMT, but cardiovascular mortality was not significantly reduced. Treatment with OACs was beneficial for all-cause mortality and non-cardiovascular mortality, irrespective of co-GDMT use; only in patients receiving all co-GDMT was OAC associated with a lower risk of non-haemorrhagic stroke/systemic embolism. Conclusion: In this large prospective, international registry on AF, comprehensive co-GDMT was associated with a lower risk of mortality in patients with AF and CHA2DS2-VASc ≥ 2 (excluding sex); OAC therapy was associated with reduced all-cause mortality and non-cardiovascular mortality, irrespective of co-GDMT use. Clinical Trial Registration: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.
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Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento , Aspirina , Infarto do Miocárdio/tratamento farmacológico , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Quimioterapia CombinadaRESUMO
The management of atrial fibrillation (AF), the most common sustained arrhythmia, impacts healthcare resource utilization (HCRU). This study aims to estimate global resource use in AF patients, using the GARFIELD-AF registry. A prospective cohort study was conducted to characterize HCRU in AF patients enrolled in sequential cohorts from 2012 to 2016 in 35 countries. Components of HCRU studied were hospital admissions, outpatient care visits, and diagnostic and interventional procedures occurring during follow-up. AF-related HCRU was reported as the percentage of patients demonstrating at least one event and was quantified as rate-per-patient-per-year (PPPY) over time. A total of 49,574 patients was analyzed, having an overall median follow-up of 719 days. Almost all patients (99.5%) had at least one outpatient care visit, while hospital admissions were the second most frequent medical contact, with similar proportions in North America (37.5%) and Europe (37.2%), and slightly higher in the other GARFIELD-AF countries (42.0%; namely Australia, Egypt, and South Africa). Asia and Latin America showed lower percentages of hospitalizations, outpatient care visits, and diagnostic and interventional procedures. Analyses of GARFIELD-AF highlighted the vast AF-related HCRU, underlying significant geographical differences in the type, quantity, and frequency of AF-related HCRU. These differences were likely attributable to health service availability and differing models of care.
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Antiplatelet therapy is considered essential for secondary prevention of ischemic heart disease. After percutaneous coronary intervention (PCI), temporary dual antiplatelet therapy (DAPT), a combination consisting of aspirin and an oral P2Y12 receptor blocker, is recommended. In the long term, this strategy results in more bleeding than antiplatelet therapy with aspirin alone. Therefore, to reduce bleeding, an increasing trend has been to keep DAPT as short as clinically acceptable, after which aspirin monotherapy is continued. Another option to diminish bleeding is to discontinue aspirin at the moment of DAPT cessation after PCI, and to continue on P2Y12 blocker monotherapy. This survey reviews the evidence on P2Y12 blocker monotherapy. Some clinical guidance will be provided on when and in whom P2Y12 inhibitor monotherapy may be applied after DAPT cessation following PCI.
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Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Humanos , Aspirina/uso terapêutico , Quimioterapia Combinada , Terapia Antiplaquetária Dupla/métodos , Hemorragia/prevenção & controle , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Resultado do TratamentoRESUMO
The first international guidance on antithrombotic therapy in the elderly came from the European Society of Cardiology Working Group on Thrombosis in 2015. This same group has updated its previous report on antiplatelet and anticoagulant drugs for older patients with acute or chronic coronary syndromes, atrial fibrillation, or undergoing surgery or procedures typical of the elderly (transcatheter aortic valve implantation and left atrial appendage closure). The aim is to provide a succinct but comprehensive tool for readers to understand the bases of antithrombotic therapy in older patients, despite the complexities of comorbidities, comedications and uncertain ischaemic- vs. bleeding-risk balance. Fourteen updated consensus statements integrate recent trial data and other evidence, with a focus on high bleeding risk. Guideline recommendations, when present, are highlighted, as well as gaps in evidence. Key consensus points include efforts to improve medical adherence through deprescribing and polypill use; adoption of universal risk definitions for bleeding, myocardial infarction, stroke and cause-specific death; multiple bleeding-avoidance strategies, ranging from gastroprotection with aspirin use to selection of antithrombotic-drug composition, dosing and duration tailored to multiple variables (setting, history, overall risk, age, weight, renal function, comedications, procedures) that need special consideration when managing older adults.
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Fibrilação Atrial , Acidente Vascular Cerebral , Substituição da Valva Aórtica Transcateter , Humanos , Idoso , Fibrinolíticos/efeitos adversos , Resultado do Tratamento , Aspirina/efeitos adversos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Anticoagulantes , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/tratamento farmacológico , Fibrilação Atrial/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversosRESUMO
Lipid-lowering agents and antiplatelet drugs are guideline-recommended standard treatment for secondary prevention of acute thrombotic events in patients with increased cardiovascular risk. Aspirin is the most frequently used antiplatelet drug, either alone or in combination with other antiplatelet agents (P2Y12 inhibitors), while statins are first-line treatment of hypercholesterolemia. The well-established mode of action of aspirin is inhibition of platelet-dependent thromboxane formation. In addition, aspirin also improves endothelial oxygen defense via enhanced NO formation and inhibits thrombin formation. Low-dose aspirin exerts in addition anti-inflammatory effects, mainly via inhibition of platelet-initiated activation of white cells.Statins inhibit platelet function via reduction of circulating low-density lipoprotein-cholesterol (LDL-C) levels and a more direct inhibition of platelet function. This comprises inhibition of thromboxane formation via inhibition of platelet phospholipase A2 and inhibition of (ox)LDL-C-mediated increases in platelet reactivity via the (ox)LDL-C receptor (CD36). Furthermore, statins upregulate endothelial NO-synthase and improve endothelial oxygen defense by inhibition of NADPH-oxidase. PCSK9 antibodies target a serine protease (PCSK9), which promotes the degradation of the LDL-C receptor impacting on LDL-C plasma levels and (ox)LDL-C-receptor-mediated signaling in platelets similar to but more potent than statins.These functionally synergistic actions are the basis for numerous interactions between antiplatelet and these lipid-lowering drugs, which may, in summary, reduce the incidence of atherothrombotic vascular events.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Aspirina , LDL-Colesterol , Interações Medicamentosas , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/uso terapêutico , Inibidores de PCSK9 , Inibidores da Agregação Plaquetária/uso terapêutico , Pró-Proteína Convertase 9/metabolismo , TromboxanosRESUMO
Dual antiplatelet therapy (DAPT) for 6-12 months, followed by lifelong aspirin monotherapy is considered an effective standard therapy for the prevention of thrombo-ischemic events in patients with acute and chronic coronary syndrome (ACS, CCS) undergoing percutaneous coronary intervention (PCI) or after a primarily conservative treatment decision. In ACS patients, the stronger P2Y12-inhibitors ticagrelor or prasugrel are recommended in combination with aspirin unless the individual bleeding risk is high and shortening of DAPT is warranted or clopidogrel is preferred. However, also in patients at low individual bleeding risk, DAPT is associated with a higher risk of bleeding. In recent years, new antithrombotic treatment strategies, such as shortening DAPT followed by early P2Y12-inhibitor monotherapy and de-escalating DAPT from potent P2Y12-inhibitors to clopidogrel by maintaining DAPT duration time, have been investigated in clinical trials and shown to reduce bleeding complications in cardiovascular high-risk patients without negative effects on ischemic events. In this review, we summarize the current knowledge and discuss its implication on future antithrombotic strategies in terms of a personalized medicine.
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OBJECTIVE: In patients with newly diagnosed atrial fibrillation (AF), do baseline risk factors and stroke prevention strategies account for the geographically diverse outcomes. DESIGN: Global Anticoagulant Registry in the FIELD-Atrial Fibrillation is a prospective multinational non-interventional registry of patients with newly diagnosed AF (n=52 018 patients). SETTING: Investigator sites (n=1317) were representative of the care settings/locations in each of the 35 participating countries. Treatment decisions were all determined by the local responsible clinicians. PARTICIPANTS: The patients (18 years and over) with newly diagnosed AF had at least 1 investigator-determined stroke risk factor and patients were not required to meet specific thresholds of risk score for anticoagulant treatment. MAIN OUTCOMES AND MEASURES: Observed 1-year event rates and risk-standardised rates were derived. RESULTS: Rates of death, non-haemorrhagic stroke/systemic embolism and major bleeding varied more than three-to-four fold across countries even after adjustment for baseline factors and antithrombotic treatments. Rates of anticoagulation and antithrombotic treatment varied widely. Patients from countries with the highest rates of cardiovascular mortality and stroke were among the least likely to receive oral anticoagulants. Beyond anticoagulant treatment, variations in the treatment of comorbidities and lifestyle factors may have contributed to the variations in outcomes. Countries with the lowest healthcare Access and Quality indices (India, Ukraine, Argentina, Brazil) had the highest risk-standardised mortality. CONCLUSION: The variability in outcomes across countries for patients with newly diagnosed AF is not accounted for by baseline characteristics and antithrombotic treatments. Residual mortality rates were correlated with Healthcare Access and Quality indices. The findings suggest the management of patients with AF needs to not only address guideline indicated and sustained anticoagulation, but also the treatment of comorbidities and lifestyle factors. TRIAL REGISTRATION NUMBER: NCT01090362.
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Fibrilação Atrial , Acidente Vascular Cerebral , Adolescente , Adulto , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Humanos , Estudos Prospectivos , Sistema de Registros , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
AIMS: To determine whether the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) integrated risk tool predicts mortality, non-haemorrhagic stroke/systemic embolism, and major bleeding for up to 2 years after new-onset AF and to assess how this risk tool performs compared with CHA2DS2-VASc and HAS-BLED. METHODS AND RESULTS: Potential predictors of events included demographic and clinical characteristics, choice of treatment, and lifestyle factors. A Cox proportional hazards model was identified for each outcome by least absolute shrinkage and selection operator methods. Indices were evaluated in comparison with CHA2DS2-VASc and HAS-BLED risk predictors. Models were validated internally and externally in ORBIT-AF and Danish nationwide registries. Among the 52 080 patients enrolled in GARFIELD-AF, 52 032 had follow-up data. The GARFIELD-AF risk tool outperformed CHA2DS2-VASc for all-cause mortality in all cohorts. The GARFIELD-AF risk score was superior to CHA2DS2-VASc for non-haemorrhagic stroke, and it outperformed HAS-BLED for major bleeding in internal validation and in the Danish AF cohort. In very low- to low-risk patients [CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)], the GARFIELD-AF risk score offered strong discriminatory value for all the endpoints when compared to CHA2DS2-VASc and HAS-BLED. The GARFIELD-AF tool also included the effect of oral anticoagulation (OAC) therapy, thus allowing clinicians to compare the expected outcome of different anticoagulant treatment decisions [i.e. no OAC, non-vitamin K antagonist (VKA) oral anticoagulants, or VKAs]. CONCLUSIONS: The GARFIELD-AF risk tool outperformed CHA2DS2-VASc at predicting death and non-haemorrhagic stroke, and it outperformed HAS-BLED for major bleeding in overall as well as in very low- to low-risk group patients with AF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF: NCT01090362, ORBIT-AF I: NCT01165710; ORBIT-AF II: NCT01701817.
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Fibrilação Atrial , Acidente Vascular Cerebral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Masculino , Sistema de Registros , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Oral anticoagulation (OAC) in atrial fibrillation (AF) reduces the risk of stroke/systemic embolism (SE). The impact of OAC discontinuation is less well documented. OBJECTIVE: Investigate outcomes of patients prospectively enrolled in the Global Anticoagulant Registry in the Field-Atrial Fibrillation study who discontinued OAC. METHODS: Oral anticoagulation discontinuation was defined as cessation of treatment for ≥7 consecutive days. Adjusted outcome risks were assessed in 23 882 patients with 511 days of median follow-up after discontinuation. RESULTS: Patients who discontinued (n = 3114, 13.0%) had a higher risk (hazard ratio [95% CI]) of all-cause death (1.62 [1.25-2.09]), stroke/systemic embolism (SE) (2.21 [1.42-3.44]) and myocardial infarction (MI) (1.85 [1.09-3.13]) than patients who did not, whether OAC was restarted or not. This higher risk of outcomes after discontinuation was similar for patients treated with vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) (p for interactions range = 0.145-0.778). Bleeding history (1.43 [1.14-1.80]), paroxysmal vs. persistent AF (1.15 [1.02-1.29]), emergency room care setting vs. office (1.37 [1.18-1.59]), major, clinically relevant nonmajor, and minor bleeding (10.02 [7.19-13.98], 2.70 [2.24-3.25] and 1.90 [1.61-2.23]), stroke/SE (4.09 [2.55-6.56]), MI (2.74 [1.69-4.43]), and left atrial appendage procedures (4.99 [1.82-13.70]) were predictors of discontinuation. Age (0.84 [0.81-0.88], per 10-year increase), history of stroke/transient ischemic attack (0.81 [0.71-0.93]), diabetes (0.88 [0.80-0.97]), weeks from AF onset to treatment (0.96 [0.93-0.99] per week), and permanent vs. persistent AF (0.73 [0.63-0.86]) were predictors of lower discontinuation rates. CONCLUSIONS: In GARFIELD-AF, the rate of discontinuation was 13.0%. Discontinuation for ≥7 consecutive days was associated with significantly higher all-cause mortality, stroke/SE, and MI risk. Caution should be exerted when considering any OAC discontinuation beyond 7 days.
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Fibrilação Atrial , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Humanos , Sistema de Registros , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
Since the first report of an association between cardiac troponin (cTn) and adverse outcome in hypertrophic cardiomyopathy (HD), there is a paucity in confirmative data. We performed a prospective, prespecified 5-year follow-up cohort study of 135 HC patients who participated in a national multicenter project and underwent clinical evaluation, MRI (cine, LGE and T2-weighted imaging) and biomarker assessment (high-sensitivity cTnT (hs-cTnT), N-terminal pro-B-type natriuretic peptide, soluble tumorgenicity suppressor-2, Galectin-3, Growth differentiation factor-15, C-terminal Propeptide of Type I Collagen (CICP)). An elevated hs-cTnT concentration was defined as ≥14ng/L. Follow-up was systematically performed for the primary endpoint: a composite of sudden cardiac death, heart failure related death, stroke-related death, heart failure hospitalization, hospitalization for stroke, spontaneous sustained ventricular tachycardia (VT) or appropriate ICD discharge, and progression to NYHA class III-IV. Elevated hs-cTnT was present in 33 of 135 (24%) HC patients. During a median follow-up of 5.0 years (IQR: 4.9-5.1) 18 patients reached the primary endpoint. Using Cox regression analysis, elevated hs-cTnT was univariately associated with the primary endpoint (HR: 3.4 (95%CI: 1.4-8.7, p=0.009). Also female sex, previous syncope, previous non-sustained VT, reduced LV ejection fraction (<50%) and CICP were associated with the primary endpoint. In multivariable analysis, elevated hs-cTnT remained independently associated with outcome (aHR: 4.7 (95%CI: 1.8-12.6, p = 0.002). In conclusion, this 5-year follow-up study is the first to prospectively confirm the association of elevated hs-cTnT and adverse outcomes. In addition to established clinical variables, cTn seems the biomarker of interest to further improve risk prediction in HC, which should be evaluated in larger prospective registries.
Assuntos
Cardiomiopatia Hipertrófica/sangue , Morte Súbita Cardíaca/epidemiologia , Insuficiência Cardíaca/mortalidade , Taquicardia Ventricular/epidemiologia , Troponina T/sangue , Idoso , Proteínas Sanguíneas , Estudos de Coortes , Desfibriladores Implantáveis , Cardioversão Elétrica/estatística & dados numéricos , Feminino , Seguimentos , Galectinas/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Hospitalização/estatística & dados numéricos , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Imageamento por Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Prognóstico , Estudos Prospectivos , Acidente Vascular Cerebral/mortalidade , Taquicardia Ventricular/terapiaRESUMO
BACKGROUND: Finger plethysmography derived stroke volumes are frequently measured during tilt table testing. There are two algorithms to determine stroke volumes: Modelflow and Nexfin CO Trek. Most tilt studies used Modelflow, while there are differences between the two algorithms. OBJECTIVE: To compare stroke volume indices by Nexfin CO Trek (SVINexfinCOTrek) with suprasternal Doppler derived SVI (SVIDoppler) in healthy controls (HC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients during tilt testing. These patients may have a large SVI decrease during the tilt enabling a large range of SVI to be studied. METHODS: One hundred and fifty-four patients and 39 HC with a normal tilt test were included. Supine and end-tilt SVIDoppler and SVINexfinCOTrek were compared using the Bland-Altman analysis. Also, the effect of calibrating supine SVINexfinCOTrek to SVIDoppler was studied. RESULTS: Supine and end-tilt SVINexfinCOTrek were significantly higher than SVIDoppler: both P< 0.005. Bias, limits of agreement, and percent error (PE) were high with PE's between 37 and 43%. The calibration procedure resulted in an acceptable variance with a PE of 29%. CONCLUSIONS: SVINexfinCOTrek overestimates stroke volumes compared to SVIDoppler, leading to high PE's. Calibration reduced variance to an acceptable level, allowing SVINexfinCOTrek to be used for assessment of SVI changes during tilt testing.
Assuntos
Síndrome de Fadiga Crônica , Adulto , Humanos , Pletismografia , Volume SistólicoRESUMO
OBJECTIVES: This study evaluated the comparative effectiveness of vitamin K antagonists (VKAs), direct thrombin inhibitors (DTIs) and factor Xa inhibitors (FXaI) in patients with atrial fibrillation (AF) at risk of stroke in everyday practice. METHODS: Data from patients with AF and Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, prior Stroke, TIA, or thromboembolism, Vascular disease, Age 65-74 years, Sex category (CHA2DS2-VASc) score ≥2 (excluding gender) in the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation registry were analysed using an improved method of propensity weighting, overlap weights and Cox proportional hazards models. RESULTS: All-cause mortality, non-haemorrhagic stroke/systemic embolism (SE) and major bleeding over 2 years were compared in 25 551 patients, 7162 (28.0%) not treated with oral anticoagulant (OAC) and 18 389 (72.0%) treated with OAC (FXaI (41.8%), DTI (11.4%) and VKA (46.8%)). OAC treatment compared with no OAC treatment was associated with decreased risk of all-cause mortality (HR 0.82 (95% CI 0.74 to 0.91)) and non-haemorrhagic stroke/SE (HR 0.71 (95% CI 0.57 to 0.88)) but increased risk of major bleeding (HR 1.46 (95% CI 1.15 to 1.86)). Non-vitamin K antagonist oral anticoagulant (NOAC) use compared with no OAC treatment was associated with lower risks of all-cause mortality and non-haemorrhagic stroke/SE (HR 0.67 (95% CI 0.59 to 0.77)) and 0.65 (95% CI 0.50 to 0.86)) respectively, with no increase in major bleeding (HR 1.10 (95% CI 0.82 to 1.47)). NOAC use compared with VKA use was associated with lower risk of all-cause mortality and major bleeding (rates/100 patient-years 3.6 (95% CI 3.3 to 3.9) vs 4.8 (95% CI 4.5 to 5.2) and 1.0 (95% CI 0.9 to 1.1) vs 1.4 (95% CI 1.2 to 1.6); HR 0.79 (95% CI 0.70 to 0.89) and 0.77 (95% CI 0.61 to 0.98) respectively), with similar risk of non-haemorrhagic stroke/SE (rates/100 patient-years 0.8 (95% CI 0.7 to 0.9) versus 1.0 (95% CI 0.8 to 1.1); HR 0.96 (95% CI 0.73 to 1.25). CONCLUSION: Important benefits in terms of mortality and major bleeding were observed with NOAC versus VKA with no difference among NOAC subtypes. TRIAL REGISTRATION NUMBER: NCT01090362.