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1.
Am J Hypertens ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33197265

RESUMO

BACKGROUND: Although low sodium intake (<2g/day) and high potassium intake (>3·5g/day) are proposed as public health interventions to reduce stroke risk, there is uncertainty about the benefit and feasibility of this combined recommendation on prevention of stroke and its subtypes. METHODS: We obtained random urine samples from 9,275 cases of acute first stroke and 9,726 matched controls (8,761 matched pairs for conditional analysis) from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes. RESULTS: The mean estimated 24-hour sodium and potassium urinary excretion was 3·29g/day and 1·57g/day, with 0·01% of participants having both low sodium (<2·0g/day) and high potassium excretion (>3·5g/day). There was a moderate positive correlation between sodium and potassium excretion (r=0·4435, P<0.001) and between sodium excretion and blood pressure (P<0.001). Compared with an estimated urinary sodium excretion of 2·8-3·5g/day (second quartile, reference), higher (>4·26g/day) (OR 1.81;95%CI,1.65-2.00) and lower (<2·8g/day) sodium excretion (OR 1.39;95%CI,1.26-1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion >4·26g/day) was significantly greater (P<0.001) for intracerebral haemorrhage (ICH) (OR 2.38;95%CI,1.93-2.92) than for ischemic stroke (OR 1.67;95%CI,1.50-1.87), and greater for large vessel and small vessel ischemic stroke than for cardioembolic ischemic stroke. Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P=0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (>1·58g/day) and moderate sodium intake (2.8-3.5 g/day) was associated with the lowest risk of stroke. CONCLUSION: The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for intracerebral haemorrhage than ischemic stroke. Our data suggest that moderate sodium intake - rather than low sodium intake - combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target.

2.
N Engl J Med ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33186492

RESUMO

BACKGROUND: A polypill comprising statins, multiple blood-pressure-lowering drugs, and aspirin has been proposed to reduce the risk of cardiovascular disease. METHODS: Using a 2-by-2-by-2 factorial design, we randomly assigned participants without cardiovascular disease who had an elevated INTERHEART Risk Score to receive a polypill (containing 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril) or placebo daily, aspirin (75 mg) or placebo daily, and vitamin D or placebo monthly. We report here the outcomes for the polypill alone as compared with matching placebo, for aspirin alone as compared with matching placebo, and for the polypill plus aspirin as compared with double placebo. For the polypill-alone and polypill-plus-aspirin comparisons, the primary outcome was death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularization. For the aspirin comparison, the primary outcome was death from cardiovascular causes, myocardial infarction, or stroke. Safety was also assessed. RESULTS: A total of 5713 participants underwent randomization, and the mean follow-up was 4.6 years. The low-density lipoprotein cholesterol level was lower by approximately 19 mg per deciliter and systolic blood pressure was lower by approximately 5.8 mm Hg with the polypill and with combination therapy than with placebo. The primary outcome for the polypill comparison occurred in 126 participants (4.4%) in the polypill group and in 157 (5.5%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.63 to 1.00). The primary outcome for the aspirin comparison occurred in 116 participants (4.1%) in the aspirin group and in 134 (4.7%) in the placebo group (hazard ratio, 0.86; 95% CI, 0.67 to 1.10). The primary outcome for the polypill-plus-aspirin comparison occurred in 59 participants (4.1%) in the combined-treatment group and in 83 (5.8%) in the double-placebo group (hazard ratio, 0.69; CI, 0.50 to 0.97). The incidence of hypotension or dizziness was higher in groups that received the polypill than in their respective placebo groups. CONCLUSIONS: Combined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk. (Funded by the Wellcome Trust and others; TIPS-3 ClinicalTrials.gov number, NCT01646437.).

3.
Heart ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938772

RESUMO

AIMS: The ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial randomised patients with atrial fibrillation at risk of stroke to apixaban or warfarin. We sought to describe patients from ARISTOTLE who prematurely permanently discontinued study drug. METHODS/RESULTS: We performed a posthoc analysis of patients from ARISTOTLE who prematurely permanently discontinued study drug during the study or follow-up period. Discontinuation rates and reasons for discontinuation were described. Death, thromboembolism (stroke, transient ischaemic attack, systemic embolism), myocardial infarction and major bleeding rates were stratified by ≤30 days or >30 days after discontinuation. A total of 4063/18 140 (22.4%) patients discontinued study drug at a median of 7.3 (2.2, 15.2) months after randomisation. Patients with discontinuation were more likely to be female and had a higher prevalence of cardiovascular disease, diabetes, renal impairment and anaemia. Premature permanent discontinuation was more common in those randomised to warfarin than apixaban (23.4% vs 21.4%; p=0.002). The most common reasons for discontinuation were patient request (46.1%) and adverse event (34.9%), with no significant difference between treatment groups. The cumulative incidence of clinical events ≤30 days after premature permanent discontinuation for all-cause death, thromboembolism, myocardial infarction, and major bleeding was 5.8%, 2.6%, 0.9%, and 3.0%, respectively. No significant difference was seen between treatment groups with respect to clinical outcomes after discontinuation. CONCLUSION: Premature permanent discontinuation of study drug in ARISTOTLE was common, less frequent in patients receiving apixaban than warfarin and was followed by high 30-day rates of death, thromboembolism and major bleeding. Initiatives are needed to reduce discontinuation of oral anticoagulation.

4.
Lancet Neurol ; 19(7): 582-590, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32562683

RESUMO

BACKGROUND: Diabetes is an independent risk factor for cognitive impairment. We aimed to investigate the association between the glucagon-like peptide-1 (GLP-1) receptor agonist dulaglutide and cognitive impairment as an exploratory analysis within the Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) trial. METHODS: REWIND is a randomised, double-blind placebo-controlled trial at 371 sites in 24 countries. We included men and women (aged ≥50 years) with either established or newly diagnosed type 2 diabetes and additional cardiovascular risk factors, glycated haemoglobin of up to 9·5% (80 mmol/mol) on a maximum of two oral glucose-lowering drugs with or without basal insulin, and a body-mass index of at least 23 kg/m2. Participants were randomly assigned (1:1) subcutaneous injections once a week of either dulaglutide (1·5 mg) or an equal volume of matching placebo. Randomisation was done using a computer-generated code with stratification by site. Participants and all study personnel were masked to treatment allocation until the database was locked. Participants were followed up at least every 6 months for the composite primary outcome of stroke, myocardial infarction, or death from cardiovascular or unknown causes. Cognitive function was assessed at baseline and during follow-up using the Montreal Cognitive Assessment (MoCA) and Digit Symbol Substitution Test (DSST). We present here the exploratory primary cognitive outcome, which was the first occurrence of a follow-up score on MoCA or DSST that was 1·5 SDs or more below the baseline mean score in the participant's country. All analyses were done using an intention-to-treat approach. The REWIND trial is registered with ClinicalTrials.gov, NCT01394952. FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were randomly assigned to either dulaglutide (n=4949) or placebo (n=4952). During median follow-up of 5·4 (IQR 5·1-5·9) years, 8828 participants provided a baseline and one or more follow-up MoCA or DSST scores, of whom 4456 were assigned dulaglutide and 4372 were assigned placebo. The cognitive outcome occurred in 4·05 per 100 patient-years in participants assigned dulaglutide and 4·35 per 100 patient-years in people assigned placebo (hazard ratio [HR] 0·93, 95% CI 0·85-1·02; p=0·11). After post-hoc adjustment for individual standardised baseline scores, the hazard of substantive cognitive impairment was reduced by 14% in those assigned dulaglutide (HR 0·86, 95% CI 0·79-0·95; p=0·0018). INTERPRETATION: Long-term treatment with dulaglutide might reduce cognitive impairment in people with type 2 diabetes. Further studies of this drug focused on brain health and cognitive function are clearly indicated. FUNDING: Eli Lilly and Company.


Assuntos
Disfunção Cognitiva/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hipoglicemiantes/uso terapêutico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Adulto , Idoso , Disfunção Cognitiva/etiologia , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Feminino , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
5.
Anesthesiology ; 132(4): 692-701, 2020 04.
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.


Assuntos
Analgésicos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Clonidina/administração & dosagem , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/diagnóstico , Idoso , Analgésicos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Clonidina/efeitos adversos , Feminino , Seguimentos , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Assistência Perioperatória/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Fatores de Tempo
6.
Int J Cardiol ; 302: 53-58, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31932116

RESUMO

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

7.
Circ Cardiovasc Qual Outcomes ; 12(11): e005858, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31707826

RESUMO

BACKGROUND: In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab was compared with placebo, added to high-intensity or maximum tolerated statin treatment after acute coronary syndrome in 18 924 patients. Alirocumab reduced first occurrence of the primary composite end point-coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or hospitalization for unstable angina-as well as total nonfatal cardiovascular events and all-cause deaths. The present analysis determined whether alirocumab reduced total (first and subsequent) hospitalizations and death and increased days alive and out of hospital (DAOH) and percent DAOH in ODYSSEY OUTCOMES. METHODS AND RESULTS: In prespecified analyses, hazard functions for total hospitalizations and death were jointly estimated by a semiparametric model, while in post hoc analyses, DAOH and percent DAOH were compared between treatment groups with Poisson regression and one-inflated beta regression, respectively. With 16 629 total hospitalizations and 726 deaths, 331 fewer hospitalizations, and 58 fewer deaths were observed with alirocumab compared with placebo, translating to 15.6 total hospitalizations or deaths avoided with alirocumab per 1000 patient-years of assigned treatment. Alirocumab reduced total hospitalizations (hazard ratio, 0.96 [95% CI, 0.92-1.00]; P=0.04) and increased DAOH relative to placebo (rate ratio, 1.003 [95% CI, 1.000-1.007]; P=0.05), primarily through a reduction in days dead (rate ratio, 0.847 [95% CI, 0.728-0.986]; P=0.03). Patients randomized to alirocumab were also more likely to survive to the end of the study without hospitalization (odds ratio, 1.06 [95% CI, 1.00-1.13]; P=0.03). CONCLUSIONS: Alirocumab reduced total hospitalizations with corresponding small increases in DAOH and percent DAOH. These outcomes provide alternative patient-centered metrics to capture the totality of alirocumab clinical efficacy after acute coronary syndrome. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01663402.

8.
Circulation ; 140(23): 1921-1932, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31557056

RESUMO

BACKGROUND: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. METHODS: Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. RESULTS: Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). CONCLUSIONS: An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400.

9.
Am Heart J ; 216: 9-19, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31377568

RESUMO

BACKGROUND: There is a need to identify and test low-cost approaches for cardiovascular disease (CVD) risk reduction that can enable health systems to achieve such a strategy. OBJECTIVE: Community health workers (CHWs) are an integral part of health-care delivery system in lower income countries. Our aim was to assess impact of CHW based interventions in reducing CVD risk factors in rural households in India. METHODS: We performed an open-label cluster-randomized trial in 28 villages in 3 states of India with the household as a unit of randomization. Households with individuals at intermediate to high CVD risk were randomized to intervention and control groups. In the intervention group, trained CHWs delivered risk-reduction advice and monitored risk factors during 6 household visits over 12 months. Households in the non-intervention group received usual care. Primary outcomes were a reduction in systolic BP (SBP) and adherence to prescribed BP lowering drugs. RESULTS: We randomized 2312 households (3261 participants at intermediate or high risk) to intervention (1172 households) and control (1140 households). At baseline prevalence of tobacco use (48.5%) and hypertension (34.7%) were high. At 12 months, there was significant decline in SBP (mmHg) from baseline in both groups- controls 130.3 ±â€¯21 to 128.3 ±â€¯15; intervention 130.3 ±â€¯21 to 127.6 ±â€¯15 (P < .01 for before and after comparison) but there was no difference between the 2 groups at 12 months (P = .18). Adherence to antihypertensive drugs was greater in intervention vs control households (74.9% vs 61.4%, P = .001). CONCLUSION: A 12-month CHW-led intervention at household level improved adherence to prescribed drugs, but did not impact SBP. To be more impactful, a more comprehensive solution that addresses escalation and access to useful therapies is needed.


Assuntos
Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Agentes Comunitários de Saúde/organização & administração , Hipertensão/tratamento farmacológico , Comportamento de Redução do Risco , Doenças Cardiovasculares/epidemiologia , Análise por Conglomerados , Feminino , Humanos , Hipertensão/epidemiologia , Índia , Modelos Lineares , Masculino , Adesão à Medicação , Determinação de Necessidades de Cuidados de Saúde , Pobreza , Avaliação de Programas e Projetos de Saúde , Saúde Pública , População Rural
10.
CMAJ ; 191(30): E830-E837, 2019 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358597

RESUMO

BACKGROUND: Among adults undergoing contemporary noncardiac surgery, little is known about the frequency and timing of death and the associations between perioperative complications and mortality. We aimed to establish the frequency and timing of death and its association with perioperative complications. METHODS: We conducted a prospective cohort study of patients aged 45 years and older who underwent inpatient noncardiac surgery at 28 centres in 14 countries. We monitored patients for complications until 30 days after surgery and determined the relation between these complications and 30-day mortality using a Cox proportional hazards model. RESULTS: We included 40 004 patients. Of those, 715 patients (1.8%) died within 30 days of surgery. Five deaths (0.7%) occurred in the operating room, 500 deaths (69.9%) occurred after surgery during the index admission to hospital and 210 deaths (29.4%) occurred after discharge from the hospital. Eight complications were independently associated with 30-day mortality. The 3 complications with the largest attributable fractions (AF; i.e., potential proportion of deaths attributable to these complications) were major bleeding (6238 patients, 15.6%; adjusted hazard ratio [HR] 2.6, 95% confidence interval [CI] 2.2-3.1; AF 17.0%); myocardial injury after noncardiac surgery [MINS] (5191 patients, 13.0%; adjusted HR 2.2, 95% CI 1.9-2.6; AF 15.9%); and sepsis (1783 patients, 4.5%; adjusted HR 5.6, 95% CI 4.6-6.8; AF 12.0%). INTERPRETATION: Among adults undergoing noncardiac surgery, 99.3% of deaths occurred after the procedure and 44.9% of deaths were associated with 3 complications: major bleeding, MINS and sepsis. Given these findings, focusing on the prevention, early identification and management of these 3 complications holds promise for reducing perioperative mortality. Study registration: ClinicalTrials.gov, no. NCT00512109.


Assuntos
Complicações Pós-Operatórias/mortalidade , Procedimentos Cirúrgicos Operatórios/mortalidade , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/mortalidade , Estudos Prospectivos , Sepse/mortalidade
11.
Lancet ; 394(10193): 131-138, Jul. 2019. gráfico, tabela
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1046322

RESUMO

Background Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease. Methods REWIND was a multicenter, randomized, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952. Findings Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m² (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1­5·9) comprising 51 820 person years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77­0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68­0·87; p<0·0001), with HRs of 0·89 (0·78­1·01; p=0·066) for sustained decline in eGFR of 30% or more and 0·75 (0·39­1·44; p=0·39) for chronic renal replacement therapy. (AU)


Assuntos
Masculino , Pessoa de Meia-Idade , Creatinina/urina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Albuminúria/prevenção & controle , Hipoglicemiantes/administração & dosagem
12.
Lancet ; 394(10193): 131-138, 2019 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-31189509

RESUMO

BACKGROUND: Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease. METHODS: REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952. FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m2 (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1-5·9) comprising 51 820 person-years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77-0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68-0·87; p<0·0001), with HRs of 0·89 (0·78-1·01; p=0·066) for sustained decline in eGFR of 30% or more and 0·75 (0·39-1·44; p=0·39) for chronic renal replacement therapy. INTERPRETATION: Long-term use of dulaglutide was associated with reduced composite renal outcomes in people with type 2 diabetes. FUNDING: Eli Lilly and Company.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hipoglicemiantes/uso terapêutico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Idoso , Albuminúria/prevenção & controle , Creatinina/urina , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade
13.
Lancet ; 394(10193): 121-130, 2019 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-31189511

RESUMO

BACKGROUND: Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A1c (HbA1c) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control. METHODS: This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952. FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66·2 years [SD 6·5], median HbA1c 7·2% [IQR 6·6-8·1], 4589 [46·3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5·4 years (IQR 5·1-5·9), the primary composite outcome occurred in 594 (12·0%) participants at an incidence rate of 2·4 per 100 person-years in the dulaglutide group and in 663 (13·4%) participants at an incidence rate of 2·7 per 100 person-years in the placebo group (hazard ratio [HR] 0·88, 95% CI 0·79-0·99; p=0·026). All-cause mortality did not differ between groups (536 [10·8%] in the dulaglutide group vs 592 [12·0%] in the placebo group; HR 0·90, 95% CI 0·80-1·01; p=0·067). 2347 (47·4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34·1%) participants assigned to placebo (p<0·0001). INTERPRETATION: Dulaglutide could be considered for the management of glycaemic control in middle-aged and older people with type 2 diabetes with either previous cardiovascular disease or cardiovascular risk factors. FUNDING: Eli Lilly and Company.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hipoglicemiantes/uso terapêutico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Idoso , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Feminino , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle
14.
Indian J Pharmacol ; 51(1): 55-60, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031468

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is a worldwide public health problem associated with an eight- to ten-fold increase in cardiovascular mortality. Among patients with CKD, on drug treatment, we aimed to determine the characteristics, etiology, patterns and rates of drug use, and outcomes and factors determining the outcomes at 6 months. METHODS: We conducted an observational follow-up study on inpatients with CKD at a tertiary care teaching hospital in South India. We collected data on patient characteristics, comorbidities, treatments at baseline, and treatments and outcomes at 6 months. We used Chi-squared tests and Cochran's Q-test to compare categorical variables, t-tests to compare continuous variables, and a multivariable logistic regression analysis to estimate the determinants of the outcome. RESULTS: We recruited 305 patients with the mean age 52.98 (±14.89) years, 73.1% were male and 55.4% patients were from a lower-middle socioeconomic background. About 72.1% were in CKD Stage 5 and 37.0% had diabetic nephropathy. Antihypertensives (84.6%) were the most common drug class prescribed, followed by multivitamins (65.2%), proton-pump inhibitors (64.9%), and antidiabetic drugs (32.5%). There was no significant difference in rates of drug use over 6 months. Increased serum creatinine (odds ratio [OR]: 1.29 [1.04, 1.60]; P = 0.017) and lower estimated glomerular filtration rate (eGFR) (OR: 38.23 [3.92, 372.06]; P = 0.002) predicted progression of CKD, and antiplatelets reduced progression (OR: 0.278 [0.09, 0.85]; P = 0.026). CONCLUSION: Diabetic nephropathy was the most common cause of CKD. There was no change in treatments over 6 months. Low eGFR predicted progression and use of antiplatelets reduced progression of CKD. Large multicenter studies are needed to study the variability in patient characteristics, treatment and outcomes to obtain a national picture, and to enable policy changes.


Assuntos
Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Idoso , Feminino , Hospitais de Ensino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Centros de Atenção Terciária , Resultado do Tratamento
15.
J Thromb Thrombolysis ; 47(3): 345-352, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30790160

RESUMO

Warfarin is dependent on multiple hepatic enzymes for metabolism while apixaban is a substrate for P-glycoprotein (P-gp) transport and hepatic CYP3A4 metabolism. The aim of this analysis was to assess the impact of interacting medication use on the treatment effects of apixaban versus warfarin. Outcomes were compared between apixaban and warfarin using Cox proportional hazards modeling according to the use of interacting medications at randomization in ARISTOTLE (n = 18,201). Interacting medications for apixaban were identified as combined P-gp and 3A4 inhibitors or inducers while interacting medications for warfarin were defined as those highly probable for warfarin potentiation or inhibition. At randomization, 5547 (30.5%) patients were on an interacting medication, including 2722 on apixaban and 2825 on warfarin. Patients using an interacting medication were more likely to be female, taking aspirin, and have a history of prior bleeding and were less likely to have a prior stroke or transient ischemic attack. No significant differences were observed on the treatment effect of apixaban compared with warfarin in patients on and off interacting medications for outcomes including the primary efficacy outcome of stroke or systemic embolism (P for interaction = 0.79) or the primary safety outcome of major bleeding (P for interaction = 0.75). Use of interacting medications with anticoagulants occurs often in patients with atrial fibrillation. Despite the potential for altered exposure, interacting medication use was not associated with a significant change in the efficacy or safety of apixaban compared with warfarin in the ARISTOTLE trial.Trial registration ClinicalTrials.gov, NCT00412984.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Interações Medicamentosas , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Varfarina/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Embolia/induzido quimicamente , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Resultado do Tratamento , Varfarina/efeitos adversos , Adulto Jovem
16.
J Am Coll Cardiol ; 73(4): 387-396, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30428396

RESUMO

BACKGROUND: The ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial compared alirocumab with placebo, added to high-intensity or maximum-tolerated statin treatment, after acute coronary syndrome (ACS) in 18,924 patients. Alirocumab reduced the first occurrence of the primary composite endpoint and was associated with fewer all-cause deaths. OBJECTIVES: This pre-specified analysis determined the extent to which alirocumab reduced total (first and subsequent) nonfatal cardiovascular events and all-cause deaths in ODYSSEY OUTCOMES. METHODS: Hazard functions for total nonfatal cardiovascular events (myocardial infarction, stroke, ischemia-driven coronary revascularization, and hospitalization for unstable angina or heart failure) and death were jointly estimated, linked by a shared frailty accounting for patient risk heterogeneity and correlated within-patient nonfatal events. An association parameter also quantified the strength of the linkage between risk of nonfatal events and death. The model provides accurate relative estimates of nonfatal event risk if nonfatal events are associated with increased risk for death. RESULTS: With 3,064 first and 5,425 total events, 190 fewer first and 385 fewer total nonfatal cardiovascular events or deaths were observed with alirocumab compared with placebo. Alirocumab reduced total nonfatal cardiovascular events (hazard ratio: 0.87; 95% confidence interval: 0.82 to 0.93) and death (hazard ratio: 0.83; 95% confidence interval: 0.71 to 0.97) in the presence of a strong association between nonfatal and fatal event risk. CONCLUSIONS: In patients with ACS, the total number of nonfatal cardiovascular events and deaths prevented with alirocumab was twice the number of first events prevented. Consequently, total event reduction is a more comprehensive metric to capture the totality of alirocumab clinical efficacy after ACS.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Idoso , Anticorpos Monoclonais Humanizados , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade
17.
Am Heart J ; 206: 72-79, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30342297

RESUMO

BACKGROUND: It is hypothesized that in individuals without clinical cardiovascular disease (CVD), but at increased CVD risk, a 50% to 60% reduction in CVD risk could be achieved using fixed dose combination (FDC) therapy (usually comprised of multiple blood-pressure agents and a statin [with or without aspirin]) in a single "polypill". However, the impact of a polypill in preventing clinical CV events has not been evaluated in a large randomized controlled trial. METHODS: TIPS-3 is a 2x2x2 factorial randomized controlled trial that will examine the effect of a FDC polypill on major CV outcomes in a primary prevention population. This study aims to determine whether the Polycap (comprised of atenolol, ramipril, hydrochlorothiazide, and a statin) reduces CV events in persons without a history of CVD, but who are at least at intermediate CVD risk. Additional interventions in the factorial design of the study will compare the effect of (1) aspirin versus placebo on CV events (and cancer), (2) vitamin D versus placebo on the risk of fractures, and (3) the combined effect of aspirin and the Polycap on CV events. RESULTS: The study has randomized 5713 participants across 9 countries. Mean age of the study population is 63.9 years, and 53% are female. Mean INTERHEART risk score is 16.8, which is consistent with a study population at intermediate CVD risk. CONCLUSION: Results of the TIP-3 study will be key to determining the appropriateness of FDC therapy as a strategy in the global prevention of CVD.


Assuntos
Atenolol/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Hidroclorotiazida/administração & dosagem , Prevenção Primária/métodos , Ramipril/administração & dosagem , Sinvastatina/administração & dosagem , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Diuréticos/administração & dosagem , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Saúde Global , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Indian Heart J ; 70(4): 565-572, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30170654

RESUMO

Non-communicable diseases are important causes of mortality and morbidity in India. Data from the Registrar General of India, World Health Organization and Global Burden of Disease (GBD) Study have reported that cardiovascular diseases (CVD) are the most important causes of death and disability. Age-adjusted mortality from these conditions has increased by 31% in last 25 years. Case-control studies have reported that hypertension is most important risk factor for CVD in India. GBD Study has estimated that hypertension led to 1.6 million deaths and 33.9 million disability-adjusted life years in 2015 and is most important cause of disease burden in India. Intensive public health effort is required to increase its awareness, treatment and control. UN Sustainable Development Goals highlight the importance of high rates of hypertension control for achieving target of 1/3 reduction in non-communicable disease mortality by 2030. It is estimated that better hypertension control can prevent 400-500,000 premature deaths in India.


Assuntos
Hipertensão/epidemiologia , Doenças não Transmissíveis/epidemiologia , Causas de Morte/tendências , Humanos , Índia/epidemiologia , Morbidade/tendências , Fatores de Risco
19.
Lancet Glob Health ; 6(8): e914-e923, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30012272

RESUMO

INTRODUCTION: India accounts for about a fifth of cardiovascular deaths globally, but nationally representative data on mortality trends are not yet available. In this nationwide mortality study, we aimed to assess the trends in ischaemic heart disease and stroke mortality over 15 years using the Million Death Study. METHODS: We determined national and subnational cardiovascular mortality rates and trends by sex and birth cohort using cause of death ascertained by verbal autopsy from 2001 to 2013 among 2·4 million households. We derived mortality rates for ischaemic heart disease and stroke by applying mortality proportions to UN mortality estimates for India and projected the rates from 2000 to 2015. FINDINGS: Cardiovascular disease caused more than 2·1 million deaths in India in 2015 at all ages, or more than a quarter of all deaths. At ages 30-69 years, of 1·3 million cardiovascular deaths, 0·9 million (68·4%) were caused by ischaemic heart disease and 0·4 million (28·0%) by stroke. At these ages, the probability of dying from ischaemic heart disease increased during 2000-15, from 10·4% to 13·1% in men and 4·8% to 6·6% in women. Ischaemic heart disease mortality rates in rural areas increased rapidly and surpassed those in urban areas. By contrast, the probability of dying from stroke decreased from 5·7% to 5·0% in men and 5·0% to 3·9% in women. A third of premature stroke deaths occurred in the northeastern states, inhabited by a sixth of India's population, where rates increased significantly and were three times higher than the national average. The increased mortality rates of ischaemic heart disease nationally and stroke in the northeastern states were higher in the cohorts of adults born in the 1970s onwards, than in earlier decades. A large and growing proportion of the ischaemic heart disease nationally and stroke deaths in high-burden states reported earlier diagnosis of cardiovascular disease, but low medication use. INTERPRETATION: The unexpectedly diverse patterns of cardiovascular mortality require investigation to identify the role of established and new cardiovascular risk factors. Secondary prevention with effective and inexpensive long-term treatment and adult smoking cessation could prevent substantial numbers of premature deaths. Without progress against the control of cardiovascular disease in India, global goals to reduce non-communicable diseases by 2030 will be difficult to achieve. FUNDING: Fogarty International Center of the US National Institutes of Health, Dalla Lana School of Public Health, University of Toronto, Indian Council of Medical Research, and the Disease Control Priorities.


Assuntos
Isquemia Miocárdica/mortalidade , Acidente Vascular Cerebral/mortalidade , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências
20.
Lancet ; 391(10134): 2019-2027, 2018 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-29864018

RESUMO

BACKGROUND: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels. METHODS: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month. FINDINGS: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p<0·0001) than those in high-income countries, although only differences in patient characteristics explained the poorer clinical outcomes in low and middle-income countries. However across all countries, irrespective of economic level, access to a stroke unit was associated with improved use of investigations and treatments, access to other rehabilitation services, and improved survival without severe dependency (odds ratio [OR] 1·29; 95% CI 1·14-1·44; all p<0·0001), which was independent of patient casemix characteristics and other measures of care. Use of acute antiplatelet treatment was associated with improved survival (1·39; 1·12-1·72) irrespective of other patient and service characteristics. INTERPRETATION: Evidence-based treatments, diagnostics, and stroke units were less commonly available or used in low and middle-income countries. Access to stroke units and appropriate use of antiplatelet treatment were associated with improved recovery. Improved care and facilities in low-income and middle-income countries are essential to improve outcomes. FUNDING: Chest, Heart and Stroke Scotland.


Assuntos
Padrões de Prática Médica , Acidente Vascular Cerebral/terapia , Idoso , Estudos de Casos e Controles , Países Desenvolvidos , Países em Desenvolvimento , Medicina Baseada em Evidências , Feminino , Acesso aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Pobreza , Inquéritos e Questionários , Análise de Sobrevida , Resultado do Tratamento
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