RESUMO
BACKGROUND: During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. METHODS AND RESULTS: Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. CONCLUSIONS: During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death.
Assuntos
Antitrombinas/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Benzimidazóis/administração & dosagem , Embolia/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , beta-Alanina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/efeitos adversos , Fibrilação Atrial/mortalidade , Benzimidazóis/efeitos adversos , Dabigatrana , Relação Dose-Resposta a Droga , Embolia/mortalidade , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/mortalidade , Resultado do Tratamento , beta-Alanina/administração & dosagem , beta-Alanina/efeitos adversosRESUMO
BACKGROUND: Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. METHODS: We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death. RESULTS: After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02). CONCLUSIONS: Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.).
Assuntos
Amiodarona/análogos & derivados , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Amiodarona/efeitos adversos , Amiodarona/uso terapêutico , Antiarrítmicos/efeitos adversos , Antiarrítmicos/sangue , Fibrilação Atrial/sangue , Flutter Atrial/tratamento farmacológico , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/mortalidade , Doença Crônica , Digoxina/sangue , Digoxina/uso terapêutico , Método Duplo-Cego , Dronedarona , Quimioterapia Combinada , Feminino , Seguimentos , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/epidemiologia , Frequência Cardíaca/efeitos dos fármacos , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND AND PURPOSE: Intracranial hemorrhage rates are higher in Asians than non-Asians, especially in patients receiving warfarin. This randomized evaluation of long-term anticoagulation therapy subgroup analysis assessed dabigatran etexilate (DE) and warfarin effects on stroke and bleeding rates in patients from Asian and non-Asian countries. METHODS: There were 2782 patients (15%) from 10 Asian countries and 15 331 patients from 34 non-Asian countries. A Cox regression model, with terms for treatment, region, and their interaction was used. RESULTS: Rates of stroke or systemic embolism in Asians were 3.06% per year on warfarin, 2.50% per year on DE 110 mg BID (DE 110), and 1.39% per year on DE 150 mg BID (DE 150); in non-Asians, the rates were 1.48%, 1.37%, and 1.06% per year with no significant treatment-by-region interactions. Hemorrhagic stroke on warfarin occurred more often in Asians than non-Asians (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.3-4.7; P=0.007), with significant reductions for DE compared with warfarin in both Asian (DE 110 versus warfarin HR, 0.15; 95% CI, 0.03-0.66 and DE 150 versus warfarin HR, 0.22; 95% CI, 0.06-0.77) and non-Asian (DE 110 versus warfarin HR, 0.37; 95% CI, 0.19-0.72 and DE 150 versus warfarin HR, 0.28; 95% CI, 0.13-0.58) patients. Major bleeding rates in Asians were significantly lower on DE (both doses) than warfarin (warfarin 3.82% per year, DE 110 2.22% per year, and DE 150 2.17% per year). CONCLUSIONS: Hemorrhagic stroke rates were higher on warfarin in Asians versus non-Asians, despite similar blood pressure, younger age, and lower international normalized ratio values. Hemorrhagic strokes were significantly reduced by DE in both Asians and non-Asians. DE benefits were consistent across Asian and non-Asian subgroups. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.
Assuntos
Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Benzimidazóis/efeitos adversos , Hemorragias Intracranianas/etiologia , Piridinas/efeitos adversos , Acidente Vascular Cerebral/etiologia , Varfarina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Ásia/epidemiologia , Ásia/etnologia , Povo Asiático/etnologia , Benzimidazóis/administração & dosagem , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etiologia , Dabigatrana , Feminino , Humanos , Hemorragias Intracranianas/epidemiologia , Masculino , Pessoa de Meia-Idade , Piridinas/administração & dosagem , Acidente Vascular Cerebral/epidemiologia , Varfarina/administração & dosagemRESUMO
The association between serum lipids and mortality has not previously been established in Thailand. Baseline data from the Electricity Generating Authority of Thailand (EGAT) cohort study, plus a resurvey of the cohort 15 years later were analyzed. Participants were employees of EGAT: 2,702 men and 797 women. Total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were taken as predictive variables; age, sex, hypertension, diabetes, cigarette smoking, alcohol drinking, and body mass index were taken as confounders. Dependent variables were all-causes and specific causes of mortality over 17 years of follow-up. The major cause of death among men was cardiovascular disease (CVD); among women, it was cancer. Relative risks (RR) for specific causes of death, for a mmol/L increase in each lipid, were estimated after adjustment for confounding factors using Cox proportional hazards regression. TC and LDL-C were negatively associated with liver cirrhosis mortality, although it was likely that the low cholesterol concentration was a consequence of the disease. HDL-C was negatively associated with CVD mortality (RR = 0.59; 95% confidence interval [CI], 0.39-0.93), coronary heart disease (CHD) mortality (RR = 0.36; 95% CI, 0.17-0.75) and all cause-mortality (RR = 0.68; 95% CI, 0.54-0.87). TG was not associated with mortality. HDL-C is an important risk factor for CVD in middle-class urban Thais. Health promotion programs to improve lipid profiles, such as effective exercise campaigns and dietary advice, are required to increase HDL-C and to help prevent CVD and premature death in Thailand.
Assuntos
Doenças Cardiovasculares/mortalidade , Causas de Morte , Dislipidemias/mortalidade , Lipídeos/sangue , População Urbana/estatística & dados numéricos , Adulto , Doenças Cardiovasculares/etiologia , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos de Coortes , Estudos Transversais , Dislipidemias/sangue , Dislipidemias/complicações , Feminino , Seguimentos , Gastroenteropatias/etiologia , Gastroenteropatias/mortalidade , Humanos , Hepatopatias/etiologia , Hepatopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Neoplasias/mortalidade , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Tailândia/epidemiologia , Fatores de Tempo , Triglicerídeos/sangueRESUMO
BACKGROUND: Obesity is a major risk factor for cardiovascular disease, but the most predictive measure for different ethnic populations is not clear. We aimed to assess whether markers of obesity, especially waist-to-hip ratio, would be stronger indicators of myocardial infarction than body-mass index (BMI), the conventional measure. METHODS: We did a standardised case-control study of acute myocardial infarction with 27 098 participants in 52 countries (12,461 cases and 14,637 controls) representing several major ethnic groups. We assessed the relation between BMI, waist and hip circumferences, and waist-to-hip ratio to myocardial infarction overall and for each group. FINDINGS: BMI showed a modest and graded association with myocardial infarction (OR 1.44, 95% CI 1.32-1.57 top quintile vs bottom quintile before adjustment), which was substantially reduced after adjustment for waist-to-hip ratio (1.12, 1.03-1.22), and non-significant after adjustment for other risk factors (0.98, 0.88-1.09). For waist-to-hip ratio, the odds ratios for every successive quintile were significantly greater than that of the previous one (2nd quintile: 1.15, 1.05-1.26; 3rd quintile: 1.39; 1.28-1.52; 4th quintile: 1.90, 1.74-2.07; and 5th quintiles: 2.52, 2.31-2.74 [adjusted for age, sex, region, and smoking]). Waist (adjusted OR 1.77; 1.59-1.97) and hip (0.73; 0.66-0.80) circumferences were both highly significant after adjustment for BMI (p<0.0001 top vs bottom quintiles). Waist-to-hip ratio and waist and hip circumferences were closely (p<0.0001) associated with risk of myocardial infarction even after adjustment for other risk factors (ORs for top quintile vs lowest quintiles were 1.75, 1.33, and 0.76, respectively). The population-attributable risks of myocardial infarction for increased waist-to-hip ratio in the top two quintiles was 24.3% (95% CI 22.5-26.2) compared with only 7.7% (6.0-10.0) for the top two quintiles of BMI. INTERPRETATION: Waist-to-hip ratio shows a graded and highly significant association with myocardial infarction risk worldwide. Redefinition of obesity based on waist-to-hip ratio instead of BMI increases the estimate of myocardial infarction attributable to obesity in most ethnic groups.
Assuntos
Saúde Global , Infarto do Miocárdio/etiologia , Obesidade/complicações , Relação Cintura-Quadril , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Vascular mortality is increasing in economically developing countries such as Thailand but reliable data about the determinants of these changes are few. METHODS: In 1985, male and female employees of the Electricity Generating Authority of Thailand took part in a cardiovascular risk factor survey. In 1997, a follow-up survey was conducted and causes of death were determined for those subjects known to have died. Changes in levels of vascular risk factors over 12 years, and the associations of baseline risk factors with vascular mortality, were calculated. RESULTS: The 1985 survey recruited 3499 volunteers (average age 43 years) of whom 23% were female. In 1997, vital status was determined for 3318 (95%) and 2967 (85%) of the study participants were resurveyed. Mean levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP), body mass index, total cholesterol and high density lipoprotein (HDL) cholesterol all increased over the 12-year follow-up period. Over the same time, the prevalence of diabetes also rose but the proportion of current smokers decreased. Vascular diseases were the most frequent cause of death during follow-up (n = 46), were positively associated with baseline age, SBP, DBP, smoking, diabetes, male sex, and total cholesterol, and were negatively associated with HDL cholesterol. CONCLUSIONS: Levels of most vascular risk factors worsened over the 12-year period between 1985 and 1997. The associations between baseline risk factor levels and vascular mortality were consistent with those observed in other populations. Interventions that control vascular risk factors have the potential to avert much premature vascular disease in Thailand.
Assuntos
Doenças Cardiovasculares/epidemiologia , Países em Desenvolvimento/estatística & dados numéricos , Indústrias/estatística & dados numéricos , Doenças Profissionais/epidemiologia , Adulto , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Doenças Cardiovasculares/mortalidade , Colesterol/sangue , HDL-Colesterol/sangue , Diabetes Mellitus/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Doenças Profissionais/mortalidade , Prevalência , Fatores de Risco , Fatores Sexuais , Fumar/epidemiologia , Tailândia/epidemiologiaRESUMO
OBJECTIVE: Few data have linked socioeconomic status (SES) to incident hypertension, and little information on the relationship between SES and hypertension are available from developing countries. We thus investigated the long-term effects of SES on incident hypertension and changes in blood pressure in Thailand. METHODS: In 1985, baseline data were collected from 3499 participants in the Electricity Generating Authority of Thailand study. Participants were re-examined in 1997, 2002 and 2007. Logistic regression models, Cox-proportional hazard models and time-dependent covariates were used to calculate the relationship between SES and prevalent hypertension in 1985, incident hypertension in 1997 and 2007, respectively. RESULTS: The prevalence of hypertension was 20% and the level of income, but not education, was inversely related to prevalent hypertension. Adjusting for several risk factors, compared to those who had tertiary education, participants who had primary education had 30% increased risk of incident hypertension in 1997 [hazard ratio 1.30, 95% confidence interval (CI) 1.09-1.54] and 20% in 2007 (1.20, 1.05-1.37); both P for trend was less than 0.01. Participants who had higher education also had substantially lower increments in SBP and DBP across 22 years (P < 0.0001 for SBP and P = 0.015 for DBP). Level of income was similarly negatively related to the progression of SBP, with a 3.6 mmHg difference between the highest income group and the lowest (P < 0.0001). CONCLUSION: Hypertensive counseling and surveillance should be emphasized within socioeconomically disadvantaged populations.
Assuntos
Pressão Sanguínea , Hipertensão/fisiopatologia , Classe Social , Adulto , Progressão da Doença , Feminino , Humanos , Hipertensão/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Tailândia/epidemiologiaRESUMO
OBJECTIVES: This study examines the risk of acute myocardial infarction (MI) conferred by the metabolic syndrome (MS) and its individual factors in multiple ethnic populations. BACKGROUND: The risk of the MS on MI has not been well characterized, especially in multiple ethnic groups. METHODS: Participants in the INTERHEART study (n = 26,903) involving 52 countries were classified using the World Health Organization (WHO) and International Diabetes Federation (IDF) criteria for MS, and their odds ratios (ORs) for MI were compared with the individual MS component factors. RESULTS: The MS is associated with an increased risk of MI, both using the WHO (OR: 2.69; 95% confidence interval [CI]: 2.45 to 2.95) and IDF (OR: 2.20; 95% CI: 2.03 to 2.38) definitions, with corresponding population attributable risks of 14.5% (95% CI: 12.7% to 16.3%) and 16.8% (95% CI: 14.8% to 18.8%), respectively. The associations are directionally similar across all regions and ethnic groups. Using the WHO definition, the association with MI by the MS is similar to that of diabetes mellitus (OR: 2.72; 95% CI: 2.53 to 2.92) and hypertension (OR: 2.60; 95% CI: 2.46 to 2.76), and significantly stronger than that of the other component risk factors. The clustering of > or =3 risk factors with subthreshold values is associated with an increased risk of MI (OR: 1.50; 95% CI: 1.24 to 1.81) compared with having component factors with "normal" values. The IDF definition showed similar results. CONCLUSIONS: In this large-scale, multi-ethnic, international investigation, the risk of MS on MI is generally comparable to that conferred by some, but not all, of its component risk factors. The characterization of risk factors, especially continuous variables, as dichotomous will underestimate risk and decrease the magnitude of association between MS and MI.
Assuntos
Etnicidade/estatística & dados numéricos , Síndrome Metabólica/epidemiologia , Infarto do Miocárdio/epidemiologia , Distribuição por Idade , Análise Química do Sangue , Estudos de Casos e Controles , Comorbidade , Intervalos de Confiança , Feminino , Humanos , Cooperação Internacional , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/etnologia , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etnologia , Razão de Chances , Prevalência , Prognóstico , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Análise de SobrevidaRESUMO
The role of alpha-1 adrenoceptor antagonists (alpha-blockers) in the management of hypertension continues to evolve. Recent data support their use as add-on therapy in uncontrolled hypertension when used in combination with all other major classes of antihypertensive drug and there is increasing evidence suggesting that they have modest but significant beneficial effects on lipid and glucose metabolism. The availability of extended-release formulations has contributed to an excellent tolerability profile. New data from an observational analysis of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) suggest that doxazosin gastrointestinal therapeutic system (GITS) used as a third-line antihypertensive agent lowered blood pressure and caused modest reductions in plasma lipids. Furthermore, use of doxazosin in ASCOT was not associated with an increased risk of heart failure, in contrast to the earlier finding of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Overall, currently available data support the use of alpha-blockers as safe, well tolerated and effective add-on antihypertensive drugs, which have additional favourable metabolic effects.