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1.
Anesthesiology ; 132(4): 692-701, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32022771

RESUMO

BACKGROUND: The authors previously reported that perioperative aspirin and/or clonidine does not prevent a composite of death or myocardial infarction 30 days after noncardiac surgery. Moreover, aspirin increased the risk of major bleeding and clonidine caused hypotension and bradycardia. Whether these complications produce harm at 1 yr remains unknown. METHODS: The authors randomized 10,010 patients with or at risk of atherosclerosis and scheduled for noncardiac surgery in a 1:1:1:1 ratio to clonidine/aspirin, clonidine/aspirin placebo, clonidine placebo/aspirin, or clonidine placebo/aspirin placebo. Patients started taking aspirin or placebo just before surgery; those not previously taking aspirin continued daily for 30 days, and those taking aspirin previously continued for 7 days. Patients were also randomly assigned to receive clonidine or placebo just before surgery, with the study drug continued for 72 h. RESULTS: Neither aspirin nor clonidine had a significant effect on the primary 1-yr outcome, a composite of death or nonfatal myocardial infarction, with a 1-yr hazard ratio for aspirin of 1.00 (95% CI, 0.89 to 1.12; P = 0.948; 586 patients [11.8%] vs. 589 patients [11.8%]) and a hazard ratio for clonidine of 1.07 (95% CI, 0.96 to 1.20; P = 0.218; 608 patients [12.1%] vs. 567 patients [11.3%]), with effect on death or nonfatal infarction. Reduction in death and nonfatal myocardial infarction from aspirin in patients who previously had percutaneous coronary intervention at 30 days persisted at 1 yr. Specifically, the hazard ratio was 0.58 (95% CI, 0.35 to 0.95) in those with previous percutaneous coronary intervention and 1.03 (95% CI, 0.91to 1.16) in those without (interaction P = 0.033). There was no significant effect of either drug on death, cardiovascular complications, cancer, or chronic incisional pain at 1 yr (all P > 0.1). CONCLUSIONS: Neither perioperative aspirin nor clonidine have significant long-term effects after noncardiac surgery. Perioperative aspirin in patients with previous percutaneous coronary intervention showed persistent benefit at 1 yr, a plausible sub-group effect.

2.
Eur Heart J ; 41(5): 645-651, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31237939

RESUMO

AIMS: To determine the 1-year risk of stroke and other adverse outcomes in patients with a new diagnosis of perioperative atrial fibrillation (POAF) after non-cardiac surgery. METHODS AND RESULTS: The PeriOperative ISchemic Evaluation (POISE)-1 trial evaluated the effects of metoprolol vs. placebo in 8351 patients, and POISE-2 compared the effect of aspirin vs. placebo, and clonidine vs. placebo in 10 010 patients. These trials included patients with, or at risk of, cardiovascular disease who were undergoing non-cardiac surgery. For the purpose of this study, we combined the POISE datasets, excluding 244 patients who were in atrial fibrillation (AF) at the time of randomization. Perioperative atrial fibrillation was defined as new AF that occurred within 30 days after surgery. Our primary outcome was the incidence of stroke at 1 year of follow-up; secondary outcomes were mortality and myocardial infarction (MI). We compared outcomes among patients with and without POAF using multivariable adjusted Cox proportional hazards models. Among 18 117 patients (mean age 69 years, 57.4% male), 404 had POAF (2.2%). The stroke incidence 1 year after surgery was 5.58 vs. 1.54 per 100 patient-years in patients with and without POAF, adjusted hazard ratio (aHR) 3.43, 95% confidence interval (CI) 2.00-5.90; P < 0.001. Patients with POAF also had an increased risk of death (incidence 31.37 vs. 9.34; aHR 2.51, 95% CI 2.01-3.14; P < 0.001) and MI (incidence 26.20 vs. 8.23; aHR 5.10, 95% CI 3.91-6.64; P < 0.001). CONCLUSION: Patients with POAF have a significantly increased risk of stroke, MI, and death at 1 year. Intervention studies are needed to evaluate risk reduction strategies in this high-risk population.

3.
Lancet Planet Health ; 3(12): e511-e520, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31868600

RESUMO

BACKGROUND: Historical, colonial, and racist policies continue to influence the health of Indigenous people, and they continue to have higher rates of chronic diseases and reduced life expectancy compared with non-Indigenous people. We determined factors accounting for variations in cardiovascular risk factors among First Nations communities in Canada. METHODS: Men and women (n=1302) aged 18 years or older from eight First Nations communities participated in a population-based study. Questionnaires, physical measures, blood samples, MRI of preclinical vascular disease, and community audits were collected. In this cross-sectional analysis, the main outcome was the INTERHEART risk score, a measure of cardiovascular risk factor burden. A multivariable model was developed to explain the variations in INTERHEART risk score among communities. The secondary outcome was MRI-detected carotid wall volume, a measure of subclinical atherosclerosis. FINDINGS: The mean INTERHEART risk score of all communities was 17·2 (SE 0·2), and more than 85% of individuals had a risk score in the moderate to high risk range. Subclinical atherosclerosis increased significantly across risk score categories (p<0·0001). Socioeconomic advantage (-1·4 score, 95% CI -2·5 to -0·3; p=0·01), trust between neighbours (-0·7, -1·2 to -0·3; p=0·003), higher education level (-1·9, -2·9 to -0·8, p<0·001), and higher social support (-1·1, -2·0 to -0·2; p=0·02) were independently associated with a lower INTERHEART risk score; difficulty accessing routine health care (2·2, 0·3 to 4·1, p=0·02), taking prescription medication (3·5, 2·8 to 4·3; p<0·001), and inability to afford prescription medications (1·5, 0·5 to 2·6; p=0·003) were associated with a higher INTERHEART risk score. Collectively, these factors explained 28% variation in the cardiac risk score among communities. Communities with higher socioeconomic advantage and greater trust, and individuals with higher education and social support, had a lower INTERHEART risk score. Communities with difficulty accessing health care, and individuals taking or unable to afford prescription medications, had a higher INTERHEART risk score. INTERPRETATION: Cardiac risk factors are lower in communities with high socioeconomic advantage, greater trust, social support and educational opportunities, and higher where it is difficult to access health care or afford prescription medications. Strategies to optimise the protective factors and reduce barriers to health care in First Nations communities might contribute to improved health and wellbeing. FUNDING: Heart and Stroke Foundation of Canada, Canadian Partnership Against Cancer, Canadian Institutes for Health Research.

4.
Lancet ; 393(10168): 228, 2019 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-30663594
5.
Ther Adv Endocrinol Metab ; 9(8): 259-268, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30181852

RESUMO

Meglitinides such as repaglinide and nateglinide are useful to treat type 2 diabetes patients who follow a flexible lifestyle. They are short-acting insulin secretagogues and are associated with less risk of hypoglycemia, weight gain and chronic hyperinsulinemia compared with sulfonylureas. Meglitinides are the substrates of cytochrome P450 (CYP) enzymes and organic anion transporting polypeptide 1B1 (OATP1B1 transporter) and the coadministration of the drugs affecting them will result in pharmacokinetic drug interactions. This article focuses on the drug interactions of meglitinides involving CYP enzymes and OATP1B1 transporter. To prevent the risk of hypoglycemic episodes, prescribers and pharmacists must be aware of the adverse drug interactions of meglitinides.

7.
Lancet Glob Health ; 5(7): e665-e672, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28476564

RESUMO

BACKGROUND: Most data on mortality and prognostic factors in patients with heart failure come from North America and Europe, with little information from other regions. Here, in the International Congestive Heart Failure (INTER-CHF) study, we aimed to measure mortality at 1 year in patients with heart failure in Africa, China, India, the Middle East, southeast Asia and South America; we also explored demographic, clinical, and socioeconomic variables associated with mortality. METHODS: We enrolled consecutive patients with heart failure (3695 [66%] clinic outpatients, 2105 [34%] hospital in patients) from 108 centres in six geographical regions. We recorded baseline demographic and clinical characteristics and followed up patients at 6 months and 1 year from enrolment to record symptoms, medications, and outcomes. Time to death was studied with Cox proportional hazards models adjusted for demographic and clinical variables, medications, socioeconomic variables, and region. We used the explained risk statistic to calculate the relative contribution of each level of adjustment to the risk of death. FINDINGS: We enrolled 5823 patients within 1 year (with 98% follow-up). Overall mortality was 16·5%: highest in Africa (34%) and India (23%), intermediate in southeast Asia (15%), and lowest in China (7%), South America (9%), and the Middle East (9%). Regional differences persisted after multivariable adjustment. Independent predictors of mortality included cardiac variables (New York Heart Association Functional Class III or IV, previous admission for heart failure, and valve disease) and non-cardiac variables (body-mass index, chronic kidney disease, and chronic obstructive pulmonary disease). 46% of mortality risk was explained by multivariable modelling with these variables; however, the remainder was unexplained. INTERPRETATION: Marked regional differences in mortality in patients with heart failure persisted after multivariable adjustment for cardiac and non-cardiac factors. Therefore, variations in mortality between regions could be the result of health-care infrastructure, quality and access, or environmental and genetic factors. Further studies in large, global cohorts are needed. FUNDING: The study was supported by Novartis.


Assuntos
Saúde Global , Insuficiência Cardíaca/mortalidade , Modelos Estatísticos , Idoso , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores Socioeconômicos
8.
J Clin Endocrinol Metab ; 102(5): 1596-1605, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28324049

RESUMO

Context: Medical strategies targeting remission of type 2 diabetes have not been systematically studied. Objective: This trial assessed the feasibility, safety, and potential to induce remission of a short-term intensive metabolic strategy. Design: A randomized, parallel, open-label pilot trial with 83 participants followed for 52 weeks. Setting: Ambulatory care. Participants: Patients with type 2 diabetes of up to 3 years in duration. Interventions: Participants were randomized to: (1) an 8-week intensive metabolic intervention, (2) a 16-week intensive metabolic intervention, or (3) standard diabetes care. During the intensive intervention period, weight loss and normoglycemia were targeted using lifestyle approaches and treatment with metformin, acarbose, and insulin glargine. Diabetes drugs were then discontinued in the intervention groups and participants were followed for hyperglycemic relapse. Primary Outcome: On-treatment normoglycemia. Results: At 8 weeks, 50.0% of the 8-week intervention group vs 3.6% of controls achieved normoglycemia on therapy [relative risk (RR), 14.0; 95% confidence interval (CI), 1.97 to 99.38), and at 16 weeks, these percentages were 70.4% in the 16-week group and 3.6% in controls (RR, 19.7; 95% CI, 2.83 to 137.13). Twelve weeks after completion of the intervention, 21.4% of the 8-week group compared with 10.7% of controls (RR, 2.00; 95% CI, 0.55 to 7.22) and 40.7% of the 16-week group compared with 14.3% of controls (RR, 2.85; 95% CI, 1.03 to 7.87) met hemoglobin A1C criteria for complete or partial diabetes remission. Conclusions: A short course of intensive lifestyle and drug therapy achieves on-treatment normoglycemia and promotes sustained weight loss. It may also achieve prolonged, drug-free diabetes remission and strongly supports ongoing studies of novel medical regimens targeting remission.


Assuntos
Acarbose/uso terapêutico , Diabetes Mellitus Tipo 2/terapia , Dieta Redutora , Exercício , Hipoglicemiantes/uso terapêutico , Insulina Glargina/uso terapêutico , Metformina/uso terapêutico , Programas de Redução de Peso , Idoso , Assistência Ambulatorial , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Estudos de Viabilidade , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Indução de Remissão
9.
Circ Cardiovasc Interv ; 9(11)2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27815344

RESUMO

BACKGROUND: The objective of this study was to assess the efficacy of sealing intermediate nonobstructive coronary saphenous vein graft (SVG) lesions with drug-eluting stents (DES; paclitaxel- or everolimus-eluting stents) for reducing major adverse cardiac events (MACE). METHODS AND RESULTS: This was a randomized controlled multicenter clinical trial that enrolled patients with a previous coronary artery bypass graft who had developed at least 1 intermediate nonobstructive SVG lesion (30%-60% diameter stenosis by visual estimation). Patients were randomized (1:1) to DES implantation (SVG-DES) or medical treatment (SVG-MT) of the target SVG lesion. The primary efficacy outcome was the first occurrence of MACE defined as the composite of cardiac death, myocardial infarction, or coronary revascularization related to the target SVG during the duration of follow-up (minimum of 2 years). Secondary efficacy outcomes included MACE related to the target SVG lesion and overall MACE. A total of 125 patients (mean age 70±9 years, 87% men) were included, with a mean time from coronary artery bypass graft of 12±5 years. Sixty and 65 patients were allocated to the SVG-DES and SVG-MT groups, respectively. There were no events related to the target SVG at 30 days. After a median follow-up of 3.4 (interquartile range: 2.8-3.9) years, the MACE rate related to the target SVG was not significantly different in the 2 groups (SVG-DES: 15.0%, SVG-MT: 20.0%; hazard ratio, 0.65; 95% confidence interval, 0.23-1.53; P=0.33). There were no significant differences between groups in MACE related to the target SVG lesion (SVG-DES: 10.0%, SVG-MT: 16.9%; hazard ratio, 0.53; 95% confidence interval, 0.20-1.43; P=0.21) or global MACE (SVG-DES: 36.7%, SVG-MT: 44.6%; hazard ratio, 0.73; 95% confidence interval, 0.42-1.27; P=0.26). CONCLUSIONS: Sealing intermediate nonobstructive SVG lesions with DES was safe but was not associated with a significant reduction of cardiac events at 3-year follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01223443.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Ponte de Artéria Coronária/efeitos adversos , Stents Farmacológicos , Oclusão de Enxerto Vascular/terapia , Paclitaxel/administração & dosagem , Intervenção Coronária Percutânea/instrumentação , Veia Safena/transplante , Idoso , Canadá , Fármacos Cardiovasculares/efeitos adversos , Constrição Patológica , Angiografia Coronária , Ponte de Artéria Coronária/mortalidade , Feminino , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/mortalidade , Oclusão de Enxerto Vascular/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Paclitaxel/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Desenho de Prótese , Fatores de Risco , Veia Safena/diagnóstico por imagem , Veia Safena/fisiopatologia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
10.
Anesthesiology ; 125(6): 1121-1129, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27627817

RESUMO

BACKGROUND: The PeriOperative ISchemia Evaluation-2 (POISE-2) trial compared aspirin with placebo after noncardiac surgery. METHODS: The authors randomly assigned 10,010 patients undergoing noncardiac surgery to receive 200 mg aspirin or placebo 2 to 4 h before surgery and then 100 mg aspirin daily or placebo daily for up to 30 days after surgery. Herein, the authors report the effect of aspirin on venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, as well as an updated pooled analysis of randomized trials of antiplatelet therapy for VTE prevention in noncardiac surgery patients. RESULTS: Six thousand five hundred forty-eight patients (65.4%) received anticoagulant prophylaxis. VTE occurred in 53 patients (1.1%) allocated to aspirin and in 60 patients (1.2%) allocated to placebo (hazard ratio, 0.89; 95% CI, 0.61 to 1.28). Major or life-threatening bleeding occurred in 312 patients (6.3%) allocated to aspirin and in 256 patients (5.1%) allocated to placebo (hazard ratio, 1.22; 95% CI, 1.04 to 1.44). Concomitant use of anticoagulant prophylaxis did not modify the effect of aspirin on VTE or bleeding. Pooled analysis of the POISE-2 and Pulmonary Embolism Prevention trials demonstrated that symptomatic VTE occurred in 173 (1.3%) of 13,724 patients allocated to aspirin and in 246 (1.8%) of 13,730 patients allocated to placebo (odds ratio, 0.71; 95% CI, 0.56 to 0.89; heterogeneity P = 0.27; I = 17%); the impact of aspirin was very similar in those who did and did not receive pharmacologic prophylaxis. Pooled estimates for symptomatic VTE were similar to the pooled estimates for any deep vein thrombosis and pulmonary embolism from the POISE-2 trial, Pulmonary Embolism Prevention trial, and the Antiplatelet Trialists' Collaboration meta-analysis. CONCLUSIONS: Aspirin in the POISE-2 trial did not reduce VTE, but two thirds of patients received anticoagulant prophylaxis, there were few VTE events, and results were consistent with a wide range of aspirin effects. A pooled analysis of the randomized trials demonstrates evidence for the efficacy of aspirin for VTE prevention in hospitalized surgical patients.


Assuntos
Aspirina/uso terapêutico , Fibrinolíticos/uso terapêutico , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Idoso , Feminino , Humanos , Masculino , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Procedimentos Cirúrgicos Operatórios , Resultado do Tratamento
11.
Int J Cardiol ; 204: 133-41, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26657608

RESUMO

BACKGROUND: There are few data on heart failure (HF) patients from Africa, Asia, the Middle East and South America. METHODS: INTER-CHF is a prospective study that enrolled HF patients in 108 centers in 16 countries from 2012 to 2014. Consecutive ambulatory or hospitalized adult patients with HF were enrolled. Baseline data were recorded on sociodemographics, clinical characteristics, HF etiology and treatments. Age- and sex-adjusted results are reported. RESULTS: We recruited 5813 HF patients: mean(SE) age=59(0.2)years, 39% female, 65% outpatients, 31% from rural areas, 26% with HF with preserved ejection fraction, with 1294 from Africa, 2661 from Asia, 1000 from the Middle-East, and 858 from South America. Participants from Africa-closely followed by Asians-were younger, had lower literacy levels, and were less likely to have health or medication insurance or be on beta-blockers compared with participants from other regions, but were most likely to be in NYHA class IV. Participants from South America were older, had higher insurance and literacy levels, and, along with Middle Eastern participants, were more likely to be on beta-blockers, but had the lowest proportion in NYHA IV. Ischemic heart disease was the most common HF etiology in all regions except Africa where hypertensive heart disease was most common. CONCLUSIONS: INTER-CHF describes significant regional variability in socioeconomic and clinical factors, etiologies and treatments in HF patients from Africa, Asia, the Middle East and South America. Opportunities exist for improvement in health/medication insurance rates and proportions of patients on beta blockers, particularly in Africa and Asia.


Assuntos
Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Internacionalidade , África/epidemiologia , Idoso , Ásia/epidemiologia , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Oriente Médio/epidemiologia , Estudos Prospectivos , América do Sul/epidemiologia
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