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1.
Eur Heart J ; 40(46): 3782-3790, 2019 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-30932145

RESUMO

AIMS: To investigate the risk of stroke/thromboembolism (TE) and major bleeding associated with anaemia among patients with atrial fibrillation (AF). Also, to assess the effects of oral anticoagulation (OAC) and time in therapeutic range (TTR) with vitamin K antagonists according to level of haemoglobin (Hb). METHODS AND RESULTS: Through administrative registry databases, we identified all Danish patients diagnosed with AF from 1997 to 2012. We included 18 734 AF patients with recent available data on Hb. Multiple Cox regression analyses were used to estimate hazard ratios and to compute standardized absolute 1-year risks of stroke/TE and major bleeding. Among included patients, 3796 (20%) had mild anaemia (Hb 6.83-7.45 mmol/L for women and Hb 6.83-8.03 mmol/L for men) and 2562 (14%) had moderate/severe anaemia (Hb <6.83 mmol/L). Moderate/severe anaemia was associated with increased risk of major bleeding and 9.1% lower median TTR compared with no anaemia. Use of OAC was associated with reduced risk of stroke/TE among patients without anaemia [standardized absolute 1-year difference -2.5%, 95% confidence interval (CI) -3.8 to -1.7%] or with mild anaemia (-2.3%, 95% CI -2.8 to -1.8%), but not with moderate/severe anaemia, (0.03%, -1.8 to +2.8%, interaction P = 0.01). Oral anticoagulation was associated with a 5.3% (95% CI 2.1-8.7%) increased standardized absolute risk of major bleeding among AF patients with moderate/severe anaemia. CONCLUSION: Anaemia was common in patients with AF and associated with major bleeding and lower TTR. Oral anticoagulation was associated with more major bleeding, but no reduction in risk of stroke/TE among AF patients with moderate/severe anaemia.


Assuntos
Anemia/complicações , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Estudos de Coortes , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Modelos de Riscos Proporcionais , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/prevenção & controle , Vitamina K/antagonistas & inibidores
2.
Biom J ; 62(3): 751-763, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32049385

RESUMO

We are interested in the estimation of average treatment effects based on right-censored data of an observational study. We focus on causal inference of differences between t-year absolute event risks in a situation with competing risks. We derive doubly robust estimation equations and implement estimators for the nuisance parameters based on working regression models for the outcome, censoring, and treatment distribution conditional on auxiliary baseline covariates. We use the functional delta method to show that these estimators are regular asymptotically linear estimators and estimate their variances based on estimates of their influence functions. In empirical studies, we assess the robustness of the estimators and the coverage of confidence intervals. The methods are further illustrated using data from a Danish registry study.


Assuntos
Biometria/métodos , Humanos , Estudos Observacionais como Assunto , Análise de Regressão , Risco , Fatores de Tempo
3.
Circulation ; 137(10): 1027-1038, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29129827

RESUMO

BACKGROUND: The long-term probability of developing atrial fibrillation (AF) considering genetic predisposition and clinical risk factor burden is unknown. METHODS: We estimated the lifetime risk of AF in individuals from the community-based Framingham Heart Study. Polygenic risk for AF was derived using a score of ≈1000 AF-associated single-nucleotide polymorphisms. Clinical risk factor burden was calculated for each individual using a validated risk score for incident AF comprised of height, weight, systolic and diastolic blood pressure, current smoking status, antihypertensive medication use, diabetes mellitus, history of myocardial infarction, and history of heart failure. We estimated the lifetime risk of AF within tertiles of polygenic and clinical risk. RESULTS: Among 4606 participants without AF at 55 years of age, 580 developed incident AF (median follow-up, 9.4 years; 25th-75th percentile, 4.4-14.3 years). The lifetime risk of AF >55 years of age was 37.1% and was substantially influenced by both polygenic and clinical risk factor burden. Among individuals free of AF at 55 years of age, those in low-polygenic and clinical risk tertiles had a lifetime risk of AF of 22.3% (95% confidence interval, 15.4-9.1), whereas those in high-risk tertiles had a risk of 48.2% (95% confidence interval, 41.3-55.1). A lower clinical risk factor burden was associated with later AF onset after adjusting for genetic predisposition (P<0.001). CONCLUSIONS: In our community-based cohort, the lifetime risk of AF was 37%. Estimation of polygenic AF risk is feasible and together with clinical risk factor burden explains a substantial gradient in long-term AF risk.


Assuntos
Fibrilação Atrial/epidemiologia , Fibrilação Atrial/genética , Hipertensão/epidemiologia , Infarto do Miocárdio/epidemiologia , Adulto , Anti-Hipertensivos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Estudos de Coortes , Pesquisa Participativa Baseada na Comunidade , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/genética , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Estados Unidos/epidemiologia
4.
Circ Res ; 120(9): 1501-1517, 2017 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-28450367

RESUMO

The past 3 decades have been characterized by an exponential growth in knowledge and advances in the clinical treatment of atrial fibrillation (AF). It is now known that AF genesis requires a vulnerable atrial substrate and that the formation and composition of this substrate may vary depending on comorbid conditions, genetics, sex, and other factors. Population-based studies have identified numerous factors that modify the atrial substrate and increase AF susceptibility. To date, genetic studies have reported 17 independent signals for AF at 14 genomic regions. Studies have established that advanced age, male sex, and European ancestry are prominent AF risk factors. Other modifiable risk factors include sedentary lifestyle, smoking, obesity, diabetes mellitus, obstructive sleep apnea, and elevated blood pressure predispose to AF, and each factor has been shown to induce structural and electric remodeling of the atria. Both heart failure and myocardial infarction increase risk of AF and vice versa creating a feed-forward loop that increases mortality. Other cardiovascular outcomes attributed to AF, including stroke and thromboembolism, are well established, and epidemiology studies have championed therapeutics that mitigate these adverse outcomes. However, the role of anticoagulation for preventing dementia attributed to AF is less established. Our review is a comprehensive examination of the epidemiological data associating unmodifiable and modifiable risk factors for AF and of the pathophysiological evidence supporting the mechanistic link between each risk factor and AF genesis. Our review also critically examines the epidemiological data on clinical outcomes attributed to AF and summarizes current evidence linking each outcome with AF.


Assuntos
Fibrilação Atrial/epidemiologia , Fibrilação Atrial/fisiopatologia , Função Atrial , Sistema de Condução Cardíaco/fisiopatologia , Potenciais de Ação , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/genética , Fibrilação Atrial/terapia , Comorbidade , Feminino , Predisposição Genética para Doença , Frequência Cardíaca , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Grupos Raciais , Fatores de Risco , Comportamento de Redução do Risco , Fatores Sexuais
5.
Thromb J ; 17: 21, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31736658

RESUMO

BACKGROUND: We aimed to compare effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin-K antagonists (VKA) in atrial fibrillation (AF) patients with chronic kidney disease (CKD) not receiving dialysis. METHODS: By using personal identification numbers, we cross-linked individual-level data from Danish administrative registries. We identified every citizen with a prior diagnosis of AF and CKD who initiated NOAC or VKA (2011-2017). An external analysis of 727 AF patients with CKD (no dialysis) was performed to demonstrate level of kidney function in a comparable population. Study outcomes included incidents of stroke/thromboembolisms (TEs), major bleedings, myocardial infarctions (MIs), and all-cause mortality. We used Cox proportional hazards models to determine associations between oral anticoagulant treatment and outcomes. RESULTS: Of 1560 patients included, 1008 (64.6%) initiated VKA and 552 (35.4%) initiated NOAC. In a comparable population we found that 95.3% of the patients had an estimated glomerular filtration rate (eGFR) < 59 mL/min. Patients treated with NOAC had a significantly decreased risk of major bleeding (hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.26-0.84) compared to VKA. There was not found a significant association between type of anticoagulant and risk of stroke/TE (HR: 0.83, 95% CI: 0.39-1.78), MI (HR: 0.45, 95% CI: 0.18-1.11), or all-cause mortality (HR: 0.99, 95% CI: 0.77-1.26). CONCLUSION: NOAC was associated with a lower risk of major bleeding in patients with AF and CKD compared to VKA. No difference was found in risk of stroke/TE, MI, and all-cause mortality.

6.
Eur Heart J ; 39(19): 1698-1705a, 2018 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-29165556

RESUMO

Aims: We examined the risks of all-cause mortality, stroke, major bleeding, and recurrent traumatic injury associated with resumption of vitamin K antagonists (VKAs) and non-VKAs oral anticoagulants (NOACs) following traumatic injury in atrial fibrillation (AF) patients. Methods and results: This was a Danish nationwide registry-based study (2005-16), including 4541 oral anticoagulant (OAC)-treated AF patients experiencing traumatic injury (defined as traumatic brain injury, hip fracture, or traumatic torso or abdominal injury). Within 90 days following discharge from traumatic injury, 60.6% resumed VKA (median age = 80, CHA2DS2-VASc = 4, HAS-BLED = 2), 16.7% resumed NOAC (median age = 81, CHA2DS2-VASc = 4, HAS-BLED = 2), and 22.7% did not resume OAC treatment (median age = 81, CHA2DS2-VASc = 4, HAS-BLED = 3). Switch from VKA to NOAC occurred among 9.5%. Since 2009, the trend in OAC resumption increased (P-value <0.0001), in particular with NOACs (P-value <0.0001). Follow-up started 90 days after discharge, and time-varying multiple Cox regression analyses were used for comparisons. Compared with non-resumption, VKA and NOAC resumption were associated with lower hazard [95% confidence interval (CI)] of all-cause mortality [hazard ratio (HR) 0.48 (0.42-0.53) and HR 0.55 (0.47-0.66), respectively] and ischaemic stroke [HR 0.56 (0.43-0.72) and HR 0.54 (0.35-0.82), respectively], increased major bleeding hazard [HR 1.30 (1.03-1.64) and HR 1.15 (0.81-1.63), respectively], and similar hazard of recurrent traumatic injury [HR 0.93 (0.73-1.18) and HR 0.87 (0.60-1.27), respectively]. Conclusion: AF patients resuming VKA and NOAC treatment following traumatic injury have lower hazard of all-cause mortality and ischaemic stroke, increased hazard of major bleeding but without additional hazards of recurrent traumatic injury. Withholding OAC following a traumatic injury in AF patients may not be warranted.


Assuntos
Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Hemorragia/induzido quimicamente , Acidente Vascular Cerebral/induzido quimicamente , Trombose/prevenção & controle , Ferimentos e Lesões/complicações , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Causas de Morte , Feminino , Humanos , Masculino , Recidiva , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Vitamina K/antagonistas & inibidores
7.
Europace ; 20(6): e78-e86, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28666358

RESUMO

Aims: After non-vitamin K antagonist (VKA) oral anticoagulation agents (NOAC) have been approved for thrombo-embolic prophylaxis in non-valvular atrial fibrillation (NVAF), utilization of oral anticoagulants (OAC) in NVAF has changed. Contemporary shifting from a VKA to a NOAC (dabigatran, rivaroxaban, or apixaban) has not been quantified, and could help assess whether these drugs are used according to recommendations. Methods and results: Using Danish nationwide registries, we identified all VKA-experienced NVAF patients initiating a NOAC from 22 August 2011 to 31 December 2015 (shifters) and all VKA-experienced NVAF patients who were not switched to NOACs (non-shifters). Baseline characteristics and temporal utilization trends were examined. We included 62 065 patients with NVAF; of these, 19 386 (29.6%) shifted from a VKA to a NOAC (9973 (54.2%) shifted to dabigatran, 4775 (26.0%) to rivaroxaban, and 3638 (19.8%) to apixaban). Shifting was associated with lower age [odds ratio (OR) 0.95, 95% confidence interval (95% CI) 0.94-0.96 per 5 year increments], female gender (OR 1.33, 95% CI 1.28-1.38), and certain co-morbidities: more often stroke, bleeding, heart failure, and alcohol abuse, and less often hypertension, ischaemic heart disease, and diabetes. Shifting was common and initially dominated by shifting from VKA to dabigatran, but at the end of 2015, most shifters were shifted to rivaroxaban (45%) or apixaban (45%) whereas shifting to dabigatran decreased (to 10%). Conclusion: In a contemporary setting among VKA-experienced NVAF patients; VKA is still prevalent although about 30% by December 2015 had shifted to a NOAC.


Assuntos
Anticoagulantes , Fibrilação Atrial , Dabigatrana/uso terapêutico , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral , Administração Oral , Idoso , Anticoagulantes/classificação , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Dinamarca/epidemiologia , Substituição de Medicamentos/métodos , Substituição de Medicamentos/estatística & dados numéricos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Masculino , Sistema de Registros/estatística & dados numéricos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Vitamina K/antagonistas & inibidores
8.
Eur Heart J ; 38(12): 899-906, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-28110293

RESUMO

AIM: The aim of this study is to examine temporal trends in the use oral anticoagulants (OAC) as stroke prophylaxis in patients with atrial fibrillation (AF) and to examine factors associated with OAC initiation. METHODS AND RESULTS: From Danish nationwide registries, we identified patients diagnosed with AF at Danish hospitals and outpatient clinics between January 2005 and June 2015. OAC initiation was assessed from prescription fills ±180 days from date of AF diagnosis. We identified a total of 108 410 patients with newly diagnosed AF. Before 2010, 40-50% initiated OAC treatment. From 2010, OAC initiation rates increased (P < 0.0001 for trend) and by June 2015, 66.5% of the incident AF patients were initiated on OAC (74.5% increase since December 2009). Increased OAC prescription was especially seen among females and 'fragile' patients (age > 75 years and high risk of stroke). The increased OAC initiation was accompanied by introduction and increased uptake of the NOACs. By the end of the study, NOACs accounted for 72.5% of all OACs prescribed in newly diagnosed AF patients. OAC initiation was associated with male gender, age 65-74 years, few comorbidities and increased risk of stroke. CONCLUSION: Since 2010, more incident AF patients in Denmark were initiated on OAC therapy with predominant NOAC prescription. The increase was pronounced among females, among patients at high risk of stroke, and among older patients.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/complicações , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Adulto , Idoso , Fibrilação Atrial/epidemiologia , Dinamarca/epidemiologia , Revisão de Uso de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia
9.
Eur Heart J ; 38(12): 907-915, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-27742807

RESUMO

BACKGROUND: Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are widely used as stroke prophylaxis in non-valvular atrial fibrillation (AF), but comparative data are sparse. PURPOSE: To compare dabigatran, rivaroxaban, and apixaban vs. VKA and the risk of stroke/thromboembolism (TE) and intracranial bleeding in AF. METHODS: Using Danish nationwide registries (2011-15), anticoagulant-naïve AF patients were identified when initiating VKA or an NOAC. Outcomes were stroke/TE and intracranial bleeding. Multiple outcome-specific Cox regression was performed to calculate average treatment effects as standardized differences in 1-year absolute risks. RESULTS: Overall, 43 299 AF patients initiated VKA (42%), dabigatran (29%), rivaroxaban (13%), and apixaban (16%). Mean CHA2DS2-VASc (SD) score was: VKA 2.9 (1.6), dabigatran 2.7 (1.6), rivaroxaban 3.0 (1.6), and apixaban 3.1 (1.6). Within patient-specific follow-up limited to the first 2 years, 1054 stroke/TE occurred and 261 intracranial bleedings. Standardized absolute risk (95% CI) of stroke/TE at 1 year after initiation of VKA was 2.01% (1.80% to 2.21%). In relation to VKA, the absolute risk differences were for dabigatran 0.11% (-0.16% to 0.42%), rivaroxaban 0.05% (-0.33% to 0.48%), and apixaban 0.45% (-0.001% to 0.93%). For the intracranial bleeding outcome, the standardized absolute risk at 1 year was for VKA 0.60% (0.49% to 0.72%); the corresponding absolute risk differences were for dabigatran -0.34% (-0.47% to - 0.21%), rivaroxaban -0.13% (-0.33% to 0.08%), and apixaban -0.20% (-0.38% to - 0.01%). CONCLUSIONS: Among anticoagulant-naïve AF patients, treatment with NOACs was not associated with significantly lower risk of stroke/TE compared with VKA, but intracranial bleeding risk was significantly lower with dabigatran and apixaban.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/complicações , Acidente Vascular Cerebral/prevenção & controle , Varfarina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrilação Atrial/epidemiologia , Isquemia Encefálica/induzido quimicamente , Estudos de Coortes , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Dinamarca/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hemorragias Intracranianas/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Vitamina K/antagonistas & inibidores , Varfarina/efeitos adversos
10.
Stroke ; 47(11): 2707-2713, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27758943

RESUMO

BACKGROUND AND PURPOSE: We sought to determine the risk of stroke/thromboembolism and bleeding associated with reduced renal function in patients with atrial fibrillation and the risk of stroke and bleeding associated with warfarin treatment in specific estimated glomerular filtration rate (eGFR) groups. METHODS: We conducted a register-based cohort study and included patients discharged with nonvalvular atrial fibrillation from 1997 to 2011 with available eGFR. RESULTS: A total of 17 349 patients were identified with eGFR available at baseline. All levels of lower eGFR were associated with higher risk of stroke/thromboembolism and bleeding. Use of warfarin was associated with higher bleeding risk in all eGFR groups; hazard ratios 1.23 (95% confidence interval [CI], 0.97-1.56), 1.26 (95% CI, 1.14-1.40), 1.18 (95% CI, 1.07-1.31), 1.11 (95% CI, 0.87-1.42), 2.01 (95% CI, 1.14-3.54) in patients with eGFR ≥90, 60 to 89, 30 to 59, 15 to 29, and <15 mL/min per 1.73 m2, respectively. Use of warfarin was associated with lower risk of stroke/thromboembolism in patients with eGFR ≥15 mL/min per 1.73 m2; hazard ratios 0.57 (95% CI, 0.43-0.76), 0.57 (95% CI, 0.51-0.64), 0.48 (95% CI, 0.44-0.54), 0.60 (95% CI, 0.45-0.80) in patients with eGFR ≥90, 60 to 89, 30 to 59, and 15 to 29 mL/min per 1.73 m2, respectively. Use of warfarin was not associated with lower risk of stroke/thromboembolism in patients with eGFR<15 mL/min per 1.73 m2; hazard ratio 1.18 (95% CI, 0.58-2.40). CONCLUSIONS: In patients with atrial fibrillation, the risk of stroke and bleeding was associated with levels of renal function. Warfarin treatment was associated with higher risk of bleeding in all eGFR groups and lower risk of stroke in patients with eGFR≥15 mL/min per 1.73 m2.


Assuntos
Anticoagulantes/farmacologia , Fibrilação Atrial/epidemiologia , Taxa de Filtração Glomerular/fisiologia , Embolia Intracraniana/epidemiologia , Hemorragias Intracranianas/epidemiologia , Trombose Intracraniana/epidemiologia , Sistema de Registros , Insuficiência Renal Crônica/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Varfarina/farmacologia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Estudos de Coortes , Comorbidade , Dinamarca/epidemiologia , Feminino , Humanos , Hemorragias Intracranianas/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Risco , Acidente Vascular Cerebral/prevenção & controle , Varfarina/efeitos adversos
11.
Europace ; 17(8): 1215-22, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25995392

RESUMO

AIMS: To examine the risk of gastrointestinal adverse effects associated with dabigatran use compared with warfarin among patients with atrial fibrillation (AF). METHODS AND RESULTS: Patients with AF and no history of gastrointestinal diseases initiating dabigatran or warfarin were identified from Danish nationwide registries from 22 August 2011 until 31 December 2012. Patients were classified as naive or experienced users, according to prior use of oral anticoagulant (OAC) therapy. The risk of subsequent proton pump inhibitor (PPI) use, upper dyspepsia-like diagnoses (gastroesophageal reflux, gastritis, gastric, and duodenal ulcer) and gastrointestinal bleeding requiring hospitalization, gastroscopy, and discontinuation of dabigatran and warfarin was examined by cumulative incidence rates and multivariable adjusted Cox regression models. We identified five groups: OAC-naive warfarin (n = 4534); OAC-naive dabigatran 110 mg b.i.d. (dabigatran 110) (n = 1168); OAC-naive dabigatran 150 mg b.i.d. (dabigatran 150) (n = 1844); OAC-experienced dabigatran 110 (n = 1143); and OAC-experienced dabigatran 150 (n = 1748). Compared with OAC-naive warfarin, the rate of initiating PPIs was significantly increased for OAC-naive dabigatran 110 [hazard ratio (HR), 1.24; 95% confidence interval (CI), 1.02-1.50]. Other dabigatran regimes were not associated with a higher risk of initiating PPIs, upper dyspepsia-like diagnoses, gastrointestinal bleeding, or gastroscopy. The risk of discontinuation was increased for OAC-experienced dabigatran 150 (HR, 1.13; 95% CI, 1.02-1.25), but not for the other dabigatran-treated groups, relative to OAC-naive warfarin. CONCLUSION: Dabigatran was not associated with upper dyspepsia-like diagnoses or gastrointestinal bleeding requiring hospitalization, and gastroscopy. The risk of subsequent PPI use was increased for OAC-naive dabigatran 110 mg users, and the risk of discontinuation was increased for OAC-experienced dabigatran 150 mg users.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Dabigatrana/uso terapêutico , Gastroenteropatias/mortalidade , Tromboembolia/prevenção & controle , Varfarina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Causalidade , Estudos de Coortes , Comorbidade , Dabigatrana/efeitos adversos , Dinamarca/epidemiologia , Feminino , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Gastroenteropatias/induzido quimicamente , Humanos , Incidência , Masculino , Fatores de Risco , Taxa de Sobrevida , Tromboembolia/mortalidade , Resultado do Tratamento , Varfarina/efeitos adversos
12.
BMJ ; 385: e077209, 2024 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-38631726

RESUMO

OBJECTIVES: To examine how the lifetime risks of atrial fibrillation and of complications after atrial fibrillation changed over time. DESIGN: Danish, nationwide, population based cohort study. SETTING: Population of Denmark from 1 January 2000 to 31 December 2022. PARTICIPANTS: 3.5 million individuals (51.7% women and 48.3% men) who did not have atrial fibrillation at 45 years of age or older were followed up until incident atrial fibrillation, migration, death, or end of follow-up, whichever came first. All 362 721 individuals with incident atrial fibrillation (46.4% women and 53.6% men), but with no prevalent complication, were further followed up until incident heart failure, stroke, or myocardial infarction. MAIN OUTCOME MEASURES: Lifetime risk of atrial fibrillation and lifetime risks of complications after atrial fibrillation over two prespecified periods (2000-10 v 2011-22). RESULTS: The lifetime risk of atrial fibrillation increased from 24.2% in 2000-10 to 30.9% in 2011-22 (difference 6.7% (95% confidence interval 6.5% to 6.8%)). After atrial fibrillation, the most frequent complication was heart failure with a lifetime risk of 42.9% in 2000-10 and 42.1% in 2011-22 (-0.8% (-3.8% to 2.2%)). Individuals with atrial fibrillation lost 14.4 years with no heart failure. The lifetime risks of stroke and of myocardial infarction after atrial fibrillation decreased slightly between the two periods, from 22.4% to 19.9% for stroke (-2.5% (-4.2% to -0.7%)) and from 13.7% to 9.8% for myocardial infarction (-3.9% (-5.3% to -2.4%). No evidence was reported of a differential decrease between men and women. CONCLUSION: Lifetime risk of atrial fibrillation increased over two decades of follow-up. In individuals with atrial fibrillation, about two in five developed heart failure and one in five had a stroke over their remaining lifetime after atrial fibrillation diagnosis, with no or only small improvement over time. Stroke risks and heart failure prevention strategies are needed for people with atrial fibrillation.


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Infarto do Miocárdio , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Fibrilação Atrial/diagnóstico , Estudos de Coortes , Fatores de Risco , Incidência , Acidente Vascular Cerebral/epidemiologia , Infarto do Miocárdio/etiologia , Insuficiência Cardíaca/epidemiologia , Dinamarca/epidemiologia
13.
Eur Heart J Cardiovasc Pharmacother ; 10(3): 210-218, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38402466

RESUMO

BACKGROUND AND AIMS: Patients with severely reduced kidney function have been excluded from randomized controlled trials and data on the safety and efficacy of direct oral anticoagulants (DOACs) according to kidney function remain sparse. The aim was to evaluate the safety and efficacy of the DOACs across subgroups of kidney function. METHODS: Using multiple Danish nationwide registers and laboratory databases, we included patients initiated on oral anticoagulants (OACs) with atrial fibrillation and available creatinine level and followed patients for 2 years to evaluate occurrence of stroke/thromboembolism (TE) and major bleeding. RESULTS: Among 26 686 included patients, 3667 (13.7%) had an estimated glomerular filtration rate (eGFR) of 30-49 mL/min/1.73 m2 and 596 (2.2%) had an eGFR below 30 mL/min/1.73 m2. We found no evidence of differences regarding the risk of stroke/TE between the OACs (P-value interaction >0.05 for all). Apixaban was associated with a lower 2-year risk of major bleeding compared to vitamin K antagonists (VKA) [hazard ratio 0.79, 95% confidence interval (CI) 0.67-0.93], and the risk difference was significantly larger among patients with reduced kidney function (P-value interaction 0.018). Rivaroxaban was associated with a higher risk of bleeding compared to apixaban (hazard ratio 1.78, 95%CI 1.32-2.39) among patients with eGFR 30-49 mL/min/1.73 m2. CONCLUSIONS: Overall, we found no differences regarding the risk of stroke/TE, but apixaban was associated with a 21% lower relative risk of major bleeding compared to VKA. This risk reduction was even greater when comparing apixaban to VKA among patients with eGFR 15-30 mL/min/1.73 m2, and when comparing apixaban to dabigatran and rivaroxaban among patients with eGFR 30-49 mL/min/1.73 m2.


Assuntos
Fibrilação Atrial , Taxa de Filtração Glomerular , Hemorragia , Rim , Sistema de Registros , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/complicações , Masculino , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Idoso , Administração Oral , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/epidemiologia , Dinamarca/epidemiologia , Rim/fisiopatologia , Rim/efeitos dos fármacos , Resultado do Tratamento , Fatores de Risco , Medição de Risco , Fatores de Tempo , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagem , Idoso de 80 Anos ou mais , Tromboembolia/prevenção & controle , Tromboembolia/epidemiologia , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Pessoa de Meia-Idade , Piridonas/efeitos adversos , Piridonas/administração & dosagem , Pirazóis/efeitos adversos , Pirazóis/administração & dosagem
14.
Eur Heart J Cardiovasc Pharmacother ; 7(1): 20-30, 2021 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31730151

RESUMO

AIMS: In atrial fibrillation (AF) patients 150 mg b.i.d. dabigatran is the standard dose, yet guidelines recommend 110 mg b.i.d. when bleeding risk is high. It is unknown to which extend these recommendations are followed in patients switching from vitamin K antagonist (VKA) to dabigatran. The aim of this study was to investigate if AF patients are switched from VKA to the appropriate dose of dabigatran. METHODS AND RESULTS: Using nationwide registries (22 August 2011 to 31 December 2012), we identified VKA-experienced AF patients with available creatinine values who switched to dabigatran. European guidelines criteria 2012 on dabigatran dosing were examined: age ≥80 years, HAS-BLED ≥3, estimated glomerular filtration rate (eGFR)<50 mL/min/1.73 m2, or use of interacting drugs. We identified 1626 VKA-experienced AF patients who switched to dabigatran 110 mg (820 patients) or 150 mg (806 patients). Patients who switched to 110 mg compared with 150 mg were older [median age 82 years (Q1-Q3: 77-86) vs. 68 years (Q1-Q3: 64-74)], more often females (54% vs. 35%), had a higher comorbidity burden, higher proportion with CHA2DS2-VASc score ≥2 (98% vs. 80%), and more with a HAS-BLED score ≥3 (46% vs. 28%). Patients switched to 110 mg had a higher absolute risk of mortality compared with patients switched to 150 mg. Overall, 26% were inappropriately dosed and 14% were switched to 110 mg although the higher dose was indicated. Furthermore, 39% of patients switched to 150 mg fulfilled one or more criteria for 110 mg, this mostly driven by high HAS-BLED scores (28.2% of patients on 150 mg). Female sex, age ≥80 years, eGFR < 50 mL/min/1.73 m2, drugs interacting with dabigatran, and prior bleeding were associated with switch to 110 mg. Patients inappropriately dosed had similar risk of mortality as patients appropriately dosed. CONCLUSION: Among VKA-experienced AF patients one in four were switched to a dabigatran dose contrary to guideline recommendations.


Assuntos
Fibrilação Atrial , Dabigatrana , Vitamina K , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vitamina K/antagonistas & inibidores , Vitamina K/uso terapêutico
15.
Eur Heart J Cardiovasc Pharmacother ; 7(FI1): f93-f100, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32065652

RESUMO

AIMS: To compare the risk of all-cause mortality, stroke, and bleeding in patients with atrial fibrillation (AF) and valvular heart disease (VHD) treated with vitamin K antagonist (VKA) or factor Xa-inhibitors (FXa-I; rivaroxaban and apixaban). METHODS AND RESULTS: We cross-linked data from Danish nationwide registries identifying patients with AF and VHD (aortic stenosis/insufficiency, mitral insufficiency, bioprosthetic heart valves, mitral-, and aortic valve repair) initiating VKA or FXa-I between January 2014 and June 2017. Outcomes were all-cause mortality, stroke, and bleeding. Using cause-specific Cox regression, we reported the standardized absolute 2-year risk of the outcomes and absolute risk differences (ARD). We identified 1115 (41.7%), 620 (23.1%), and 942 (35.2%) patients initiating treatment with VKA, rivaroxaban, and apixaban, respectively. The standardized absolute risk (95% confidence interval) of all-cause mortality associated with VKA treatment was 34.1% (30.4-37.8%) with corresponding ARD for FXa-I of -2.7% (-6.7% to 1.4%). The standardized absolute risk of stroke for VKA was 3.8% (2.2-5.4%) with corresponding ARD for FXa-I of -0.1% (-2.0% to 1.8%). The standardized risk of bleeding for VKA was 10.4% (7.2-12.9%) with corresponding ARD for FXa-I of -2.0% (-5.1% to 1.1%). The risk of bleeding was significantly reduced in subgroup analyses of apixaban compared with VKA [ARD: -3.9% (-7.0% to -0.9%)] and rivaroxaban [ARD: -5.6% (-9.5% to -1.7%)]. CONCLUSION: In this nationwide cohort study, there were no significant differences in the risks of all-cause mortality, stroke, and bleeding in patients with AF and VHD treated with VKA compared with FXa-I.


Assuntos
Fibrilação Atrial , Doenças das Valvas Cardíacas , Acidente Vascular Cerebral , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Estudos de Coortes , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/tratamento farmacológico , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle
16.
Circ Arrhythm Electrophysiol ; 13(2): e007607, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31941368

RESUMO

BACKGROUND: Identification of protein biomarkers associated with incident atrial fibrillation (AF) may improve the understanding of the pathophysiology, risk prediction, and development of new therapeutics for AF. We examined the associations between 85 protein biomarkers and incident AF. METHODS: We included participants ≥50 years of age from the FHS (Framingham Heart Study) Offspring and Third Generation cohorts, who had 85 fasting plasma proteins measured using Luminex xMAP platform. Hazard ratios (per 1 SD increment of rank-normalized biomarker [hazard ratio]) and 95% CIs for incident AF were calculated using Cox regression models adjusted for age, sex, height, weight, current smoking, systolic blood pressure, diastolic blood pressure, hypertension treatment, diabetes mellitus, valvular heart disease, prevalent myocardial infarction, and prevalent heart failure. We used the false discovery rate to account for multiple testing. RESULTS: The study sample comprised 3378 participants (54% women) with mean (SD) age of 61.5 (8.4) years. In total, 401 developed AF over a mean follow-up of 12.3±3.8 years. We observed lower hazard of incident AF associated with higher mean levels of IGF1 (insulin-like growth factor 1; hazard ratio per 1 SD increment in protein level, 0.84 [95% CI, 0.76-0.93]), and higher hazard of incident AF associated with higher mean levels of both IGFBP1 (insulin-like growth factor-binding protein 1; hazard ratio, 1.24 [95% CI, 1.1-1.39]) and NT-proBNP (N-terminal pro-B-type natriuretic peptide; hazard ratio, 1.73 [95% CI, 1.52-1.96]). CONCLUSIONS: Decreased levels of IGF1 and increased levels of IGFBP1 and NT-proBNP were associated with higher risk of incident AF.


Assuntos
Fibrilação Atrial/fisiopatologia , Biomarcadores/sangue , Proteínas Sanguíneas/análise , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
17.
Circ Cardiovasc Qual Outcomes ; 13(4): e006058, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32283966

RESUMO

BACKGROUND: The comparative effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) is uncertain, as they have not been compared directly in randomized trials. Previous observational comparisons of NOACs are likely to be biased by unmeasured confounders. We sought to compare the efficacy and safety of rivaroxaban and apixaban for stroke prevention in patients with atrial fibrillation (AF), using practice variation in preference for NOAC as an instrumental variable. METHODS AND RESULTS: Patients started on apixaban or rivaroxaban after newly diagnosed AF were identified using Danish nationwide registries. Patients were categorized according to facility preferences for type of NOAC, independent of actual treatment, measured as fraction of the prior 20 patients with AF initiated on rivaroxaban in the same facility. Facility preference for NOAC was used as an instrumental variable. The occurrence of stroke/thromboembolism, major bleeding, myocardial infarction, and all-cause mortality over 2 years of follow-up were investigated using adjusted Cox regressions. We analyzed 6264 patients with AF initiated on rivaroxaban or apixaban. NOAC preference was strongly related to actual choice of treatment but not associated with any other measured baseline characteristics. Patients treated in facilities that had preference for rivaroxaban had more major bleeding: compared with patients treated in facilities that used rivaroxaban in 0% to 20% of cases, the adjusted hazard ratio for bleeding was 1.06 when treated in a facility with 25% to 40% use; 1.41 with 45% to 60% use; 1.51 with 65% to 80% use; and 1.81 with 0% to 100% use (Ptrend=0.01). Higher facility preference for rivaroxaban was not significantly associated with increased risk of stroke/thromboembolism (Ptrend=0.06), myocardial infarction (Ptrend=0.65), or all-cause mortality (Ptrend=0.89). When we used the instrumental variable to model the causal relationship between choice of NOAC and major bleeding, relative risk with rivaroxaban was 1.89 (95% CI, 1.06-2.72) compared with apixaban. CONCLUSIONS: Using instrumental variable estimation in a cohort of patients with AF, rivaroxaban was associated with higher risk of major bleeding compared with apixaban. No significant associations to other outcomes were found in main analyses.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Idoso , Fibrilação Atrial/mortalidade , Pesquisa Comparativa da Efetividade , Dinamarca/epidemiologia , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Sistema de Registros , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo , Resultado do Tratamento
18.
Circ Cardiovasc Qual Outcomes ; 13(4): e005918, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32228064

RESUMO

BACKGROUND: Risk prediction models for atrial fibrillation (AF) do not give information about when AF might develop. Restricted mean survival time (RMST) quantifies risk into the time domain. Our objective was to use RMST to re-express individualized AF risk predictions. METHODS AND RESULTS: We included AF-free participants from the Framingham Heart Study community-based cohorts. We predicted new-onset AF over 10-year follow-up according to baseline covariates: age, height, weight, systolic blood pressure, diastolic blood pressure, current smoking, antihypertensive treatment, diabetes mellitus, prevalent heart failure, and prevalent myocardial infarction. First, we fitted a Cox regression model and estimated the 10-year predicted risk of AF. Second, we fitted an RMST model and estimated the predicted mean time free of AF and alive over a time horizon of 10 years. We included 7586 AF-free participants contributing to 11 088 examinations (mean age 61±11 years, 44% were men). During 10-year follow-up, 822 participants developed AF. The Cox and RMST models were in agreement regarding the direction, strength, and statistical significance of associations for all covariates. Low (<5%), intermediate (5%-15%), and high (>15%) 10-year predicted risk of AF corresponded to predicted mean time alive and free of AF of 9.9, 9.6, and 8.8 years, respectively. A 60-year-old woman with a body mass index of 25 kg/m2, no use of hypertension treatment and no history of heart failure had a predicted mean time alive and free of AF of 9.9 years, whereas a 70-year-old man with a body mass index of 30 kg/m2, use of hypertension treatment, and with prevalent heart failure had a predicted mean time alive and free of AF of 7.9 years. CONCLUSIONS: The RMST can be used to develop risk prediction models to express results in a time scale. RMST may offer a complementary risk communication tool for AF in clinical practice.


Assuntos
Fibrilação Atrial/epidemiologia , Fatores Etários , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Comorbidade , Intervalo Livre de Doença , Feminino , Nível de Saúde , Humanos , Incidência , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Prevalência , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo
19.
Eur Heart J Cardiovasc Pharmacother ; 6(5): 292-300, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31742339

RESUMO

AIMS: Non-vitamin K antagonist oral anticoagulants (NOACs) are displacing vitamin K antagonists (VKAs) for stroke prophylaxis in patients with atrial fibrillation (AF). Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) could increase gastrointestinal bleeding (GIB) risks among these patients. The aim of this study was to examine the risk of GIB among Danish AF patients taking oral anticoagulants (OACs) and NSAIDs. METHODS AND RESULTS: Using nationwide administrative registries, we determined concomitant NSAID use among anticoagulant-naïve patients with AF initiating OACs between August 2011 and June 2017. We calculated short-term absolute risks differences and hazard ratios (HRs) for GIB based on multiple adjusted cause-specific Cox regressions with time-dependent NSAID treatment. Among 41 183 patients [median age 70 years (interquartile range 64-78); 55% men], 21% of patients on NOACs and 18% on VKA were co-prescribed NSAIDs. The differences in absolute risk [95% confidence interval (CI)] of GIB within 14 days of commencing concomitant NSAID therapy (vs. no concomitant NSAID therapy) were 0.10% (0.04-0.18%) for NOACs and 0.13% (0.03-0.24%) for VKA. NOACs overall were associated with less GIB than VKA [HR 0.77 (95% CI 0.69-0.85)]. Compared with OACs alone, concomitant NSAIDs doubled the GIB risk associated with NOACs overall [HR 2.01 (95% CI 1.40-2.61)] and with VKA [HR 1.95 (95% CI 1.21-2.69)]. CONCLUSION: Among this nationwide AF population taking OACs, concomitant NSAID therapy increased the short-term absolute risk of GIB. Non-vitamin K antagonist oral anticoagulants alone were associated with lower GIB risks than VKA but concomitant NSAIDs abolished this advantage. The findings align with post hoc analyses from randomized studies. Physicians should exercise appropriate caution when prescribing NSAIDs for patients with AF taking NOACs or VKA.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Hemorragia Gastrointestinal/induzido quimicamente , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anticoagulantes/administração & dosagem , Fibrilação Atrial/epidemiologia , Dinamarca/epidemiologia , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimedicação , Sistema de Registros , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Resultado do Tratamento
20.
J Am Coll Cardiol ; 74(17): 2150-2158, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31648707

RESUMO

BACKGROUND: Elderly patients in long-term treatment with vitamin K antagonists (VKAs) are at high risk of osteoporotic fractures compared with the background population. It has been speculated that the choice of oral anticoagulant (OAC) may affect the risk of osteoporotic fractures. OBJECTIVES: The risk of osteoporotic fractures was evaluated among patients with atrial fibrillation treated with VKA or direct oral anticoagulants (DOACs). METHODS: Patients were identified using the Danish national registries. Patients were included only if they had no prior use of osteoporosis medication and they had undergone 180 days of OAC treatment. Outcomes were hip fracture, major osteoporotic fracture, any fracture, initiation of osteoporosis medication, and a combined endpoint. RESULTS: Overall, 37,350 patients were included. The standardized absolute 2-year risk of any fracture was low among DOAC-treated patients (3.1%; 95% CI: 2.9% to 3.3%) and among VKA-treated patients (3.8%; 95% CI: 3.4% to 4.2%). DOAC was associated with a significantly lower relative risk of any fracture (hazard ratio [HR]: 0.85; 95% CI: 0.74 to 0.97), major osteoporotic fractures (HR: 0.85; 95% CI: 0.72 to 0.99), and initiating osteoporotic medication (HR: 0.82; 95% CI: 0.71 to 0.95). A combined endpoint showed that patients treated with DOAC had a significantly lower relative risk of experiencing any fracture or initiating osteoporosis medication (HR: 0.84; 95% CI: 0.76 to 0.93). CONCLUSIONS: In a nationwide population, the absolute risk of osteoporotic fractures was low among patients with atrial fibrillation on OAC, but DOAC was associated with a significantly lower risk of osteoporotic fractures compared with VKA.


Assuntos
Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fraturas por Osteoporose/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Comorbidade , Dinamarca/epidemiologia , Feminino , Consolidação da Fratura , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/induzido quimicamente , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Vitamina K/antagonistas & inibidores
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