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1.
Am J Hypertens ; 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31807750

RESUMO

BACKGROUND: Despite readily available treatments, control of blood pressure (BP) with population ageing remains suboptimal. Further, there are gaps in the understanding of the management of high BP in the aged. We explored antihypertensive treatment and control among elderly hypertensive participants free from overt cardiovascular disease (CVD), and identified factors related to both 'untreated' and 'treated but uncontrolled' high BP. METHODS: We analyzed baseline data from 19,114 individuals aged ≥65-years enrolled from Australia and US in the ASPirin in Reducing Events in the Elderly (ASPREE) study. Hypertension was defined as an average systolic/diastolic BP ≥140/90mmHg and/or the use of any BP lowering medication. 'Controlled hypertension' was defined if participants were receiving antihypertensive medication and BP <140&90mmHg. Descriptive analyses were used to summarize hypertension control rates; logistic regression was used to investigate relationships with treatment and BP control. RESULTS: Overall, 74% (14,213/19,114) of participants were hypertensive; and of these 29% (4,151/14,213) were untreated. Among those treated participants, 53% (5,330/10,062) had BP≥140/90 mmHg. Participants who were untreated were more likely to be men, have higher educational status, and be in good physical health, and less likely to have significant comorbidities. The factors related to 'treated but uncontrolled' BP included older age, male, Black race (versus White), using antihypertensive monotherapy (versus multiple) and residing in Australia (versus US). CONCLUSION: High levels of 'untreated' and 'treated but uncontrolled' BP occur in healthy elderly people without CVD , suggesting there are opportunities for better BP control in the primary prevention of CVD in this population.

2.
Gastroenterology ; 157(2): 403-412, Aug., 2019. tabela, grafico
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1022748

RESUMO

BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528).CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials. (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/prevenção & controle , Aspirina/administração & dosagem , Método Duplo-Cego , Relação Dose-Resposta a Droga , Hemorragia Gastrointestinal/prevenção & controle , Anticoagulantes/administração & dosagem
3.
Gastroenterology ; 157(3): 682-691, ago., 30 2019. ilus, tab
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1015771

RESUMO

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 x 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. (AU)


Assuntos
Bactérias , Doenças Cardiovasculares , Aspirina
4.
JCI Insight ; 4(13)2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31292301

RESUMO

BACKGROUNDStatins have pleiotropic effects on lipid metabolism. The relationship between these effects and future cardiovascular events is unknown. We characterized the changes in lipids upon pravastatin treatment and defined the relationship with risk reduction for future cardiovascular events.METHODSPlasma lipids (n = 342) were measured in baseline and 1-year follow-up samples from a Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study subcohort (n = 4991). The associations of changes in lipids with treatment and cardiovascular outcomes were investigated using linear and Cox regression. The effect of treatment on future cardiovascular outcomes was examined by the relative risk reduction (RRR).RESULTSPravastatin treatment was associated with changes in 206 lipids. Species containing arachidonic acid were positively associated while phosphatidylinositol species were negatively associated with pravastatin treatment. The RRR from pravastatin treatment for cardiovascular events decreased from 23.5% to 16.6% after adjustment for clinical risk factors and change in LDL-cholesterol (LDL-C) and to 3.0% after further adjustment for the change in the lipid ratio PI(36:2)/PC(38:4). Change in PI(36:2)/PC(38:4) mediated 58% of the treatment effect. Stratification of patients into quartiles of change in PI(36:2)/PC(38:4) indicated no benefit of pravastatin in the fourth quartile.CONCLUSIONThe change in PI(36:2)/PC(38:4) predicted benefit from pravastatin, independent of change in LDL-C, demonstrating its potential as a biomarker for monitoring the clinical benefit of statin treatment in secondary prevention.TRIAL REGISTRATIONAustralian New Zealand Clinical Trials Registry identifier ACTRN12616000535471.FUNDINGBristol-Myers Squibb; NHMRC grants 211086, 358395, and 1029754; NHMRC program grant 1149987; NHMRC fellowship 108026; and the Operational Infrastructure Support Program of the Victorian government of Australia.

5.
J Rheumatol ; 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31154415

RESUMO

OBJECTIVE: Vascular pathology (changes in blood vessels) and osteoarthritis (OA) are both common chronic conditions associated with aging and obesity, but whether vascular pathology is a risk factor for OA is unclear. The aim of this study was to systematically review the evidence for an association between vascular pathology and risk of joint-specific OA. METHODS: Scopus, Ovid Medline, and EMBASE were searched from inception to February 2019. MeSH terms and keywords were used to identify studies examining the association between vascular pathology and OA. Two reviewers independently extracted the data and assessed the methodological quality. Qualitative evidence synthesis was performed. RESULTS: Fifteen studies with high (n = 3), fair (n = 3), or low (n = 9) quality were included. Features of vascular pathology included atherosclerosis, vascular stiffness, and endothelial dysfunction in different vascular beds. There was evidence for an association between vascular pathology and risk of hand OA in women but not men, and between vascular pathology and risk of knee OA in both men and women. Only 2 studies examined hip OA showing no association between vascular pathology and risk of hip OA. CONCLUSION: There is evidence suggesting an association between vascular pathology and risk of hand and knee OA, with a potential causal relationship for knee OA. Based on the limited evidence, it is hard to conclude an association for hip OA. Further stronger evidence is needed to determine whether there is a causal relationship.

6.
Eur Heart J ; 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31209498

RESUMO

AIMS: Distinct ceramide lipids have been shown to predict the risk for cardiovascular disease (CVD) events, especially cardiovascular death. As phospholipids have also been linked with CVD risk, we investigated whether the combination of ceramides with phosphatidylcholines (PCs) would be synergistic in the prediction of CVD events in patients with atherosclerotic coronary heart disease in three independent cohort studies. METHODS AND RESULTS: Ceramides and PCs were analysed using liquid chromatography-mass spectrometry (LC-MS) in three studies: WECAC (The Western Norway Coronary Angiography Cohort) (N = 3789), LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease) trial (N = 5991), and KAROLA (Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung) (N = 1023). A simple risk score, based on the ceramides and PCs showing the best prognostic features, was developed in the WECAC study and validated in the two other cohorts. This score was highly significant in predicting CVD mortality [multiadjusted hazard ratios (HRs; 95% confidence interval) per standard deviation were 1.44 (1.28-1.63) in WECAC, 1.47 (1.34-1.61) in the LIPID trial, and 1.69 (1.31-2.17) in KAROLA]. In addition, a combination of the risk score with high-sensitivity troponin T increased the HRs to 1.63 (1.44-1.85) and 2.04 (1.57-2.64) in WECAC and KAROLA cohorts, respectively. The C-statistics in WECAC for the risk score combined with sex and age was 0.76 for CVD death. The ceramide-phospholipid risk score showed comparable and synergistic predictive performance with previously published CVD risk models for secondary prevention. CONCLUSION: A simple ceramide- and phospholipid-based risk score can efficiently predict residual CVD event risk in patients with coronary artery disease.

7.
Gastroenterology ; 157(3): 682-691.e2, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31152740

RESUMO

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.


Assuntos
Aspirina/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Hemorragia Gastrointestinal/prevenção & controle , Pantoprazol/administração & dosagem , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Rivaroxabana/administração & dosagem , Idoso , Aspirina/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Método Duplo-Cego , Esquema de Medicação , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/microbiologia , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol/efeitos adversos , Doença Arterial Periférica/diagnóstico , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
8.
Gastroenterology ; 157(2): 403-412.e5, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31054846

RESUMO

BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528). CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.


Assuntos
Anticoagulantes/efeitos adversos , Doenças Cardiovasculares/prevenção & controle , Hemorragia Gastrointestinal/prevenção & controle , Pantoprazol/administração & dosagem , Úlcera Péptica/prevenção & controle , Inibidores da Bomba de Prótons/administração & dosagem , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/epidemiologia , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Resultado do Tratamento
9.
Med J Aust ; 210(9): 409-415, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30907001

RESUMO

OBJECTIVES: To examine the effectiveness of different strategies for recruiting participants for a large Australian randomised controlled trial (RCT), the Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE). DESIGN, SETTING, PARTICIPANTS: Men and women aged 55-60 years with at least two cardiovascular risk factors (hypertension, hypercholesterolaemia, overweight/obesity) were recruited for a multicentre placebo-controlled RCT assessing the effectiveness of 23-valent pneumococcal polysaccharide vaccine (23vPPV) for preventing cardiovascular events. METHODS: Invitations were mailed by the Australian Department of Human Services to people in the Medicare database aged 55-60 years; reminders were sent 2 weeks later. Invitees could respond in hard copy or electronically. Direct recruitment was supplemented by asking invitees to extend the invitation to friends and family (snowball sampling) and by Facebook advertising. MAIN OUTCOME: Proportions of invitees completing screening questionnaire and recruited for participation in the RCT. RESULTS: 21 526 of 154 992 invited people (14%) responded by completing the screening questionnaire, of whom 4725 people were eligible and recruited for the study. Despite the minimal study burden (one questionnaire, one clinic visit), the overall participation rate was 3%, or an estimated 10% of eligible persons. Only 16% of eventual participants had responded within 2 weeks of the initial invitation letter (early responders); early and late responders did not differ in their demographic or medical characteristics. Socio-economic disadvantage did not markedly influence response rates. Facebook advertising and snowball sampling did not increase recruitment. CONCLUSIONS: Trial participation rates are low, and multiple concurrent methods are needed to maximise recruitment. Social media strategies may not be successful in older age groups. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12615000536561.

11.
Int J Stroke ; 14(3): 270-281, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30058959

RESUMO

BACKGROUND: Covert vascular disease of the brain manifests as infarcts, white matter hyperintensities, and microbleeds on MRI. Their cumulative effect is often a decline in cognition, motor impairment, and psychiatric disorders. Preventive therapies for covert brain ischemia have not been established but represent a huge unmet clinical need. AIMS: The MRI substudy examines the effects of the antithrombotic regimens in COMPASS on incident covert brain infarcts (the primary outcome), white matter hyperintensities, and cognitive and functional status in a sample of consenting COMPASS participants without contraindications to MRI. METHODS: COMPASS is a randomized superiority trial testing rivaroxaban 2.5 mg bid plus acetylsalicylic acid 100 mg and rivaroxaban 5 mg bid against acetylsalicylic acid 100 mg per day for the combined endpoint of MI, stroke, and cardiovascular death in individuals with stable coronary artery disease or peripheral artery disease. T1-weighted, T2-weighted, T2*-weighted, and FLAIR images were obtained close to randomization and near the termination of assigned antithrombotic therapy; biomarker and genetic samples at randomization and one month, and cognitive and functional assessment at randomization, after two years and at the end of study. RESULTS: Between March 2013 and May 2016, 1905 participants were recruited from 86 centers in 16 countries. Of these participants, 1760 underwent baseline MRI scans that were deemed technically adequate for interpretation. The mean age at entry of participants with interpretable MRI was 71 years and 23.5% were women. Coronary artery disease was present in 90.4% and 28.1% had peripheral artery disease. Brain infarcts were present in 34.8%, 29.3% had cerebral microbleeds, and 93.0% had white matter hyperintensities. The median Montreal Cognitive Assessment score was 26 (interquartile range 23-28). CONCLUSIONS: The COMPASS MRI substudy will examine the effect of the antithrombotic interventions on MRI-determined covert brain infarcts and cognition. Demonstration of a therapeutic effect of the antithrombotic regimens on brain infarcts would have implications for prevention of cognitive decline and provide insight into the pathogenesis of vascular cognitive decline.

12.
Lancet ; 392(10155): 1311-1320, 2018 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-30293769

RESUMO

BACKGROUND: Elevated lipoprotein(a) is a genetic risk factor for cardiovascular disease in general population studies. However, its contribution to risk for cardiovascular events in patients with established cardiovascular disease or on statin therapy is uncertain. METHODS: Patient-level data from seven randomised, placebo-controlled, statin outcomes trials were collated and harmonised to calculate hazard ratios (HRs) for cardiovascular events, defined as fatal or non-fatal coronary heart disease, stroke, or revascularisation procedures. HRs for cardiovascular events were estimated within each trial across predefined lipoprotein(a) groups (15 to <30 mg/dL, 30 to <50 mg/dL, and ≥50 mg/dL, vs <15 mg/dL), before pooling estimates using multivariate random-effects meta-analysis. FINDINGS: Analyses included data for 29 069 patients with repeat lipoprotein(a) measurements (mean age 62 years [SD 8]; 8064 [28%] women; 5751 events during 95 576 person-years at risk). Initiation of statin therapy reduced LDL cholesterol (mean change -39% [95% CI -43 to -35]) without a significant change in lipoprotein(a). Associations of baseline and on-statin treatment lipoprotein(a) with cardiovascular disease risk were approximately linear, with increased risk at lipoprotein(a) values of 30 mg/dL or greater for baseline lipoprotein(a) and 50 mg/dL or greater for on-statin lipoprotein(a). For baseline lipoprotein(a), HRs adjusted for age and sex (vs <15 mg/dL) were 1·04 (95% CI 0·91-1·18) for 15 mg/dL to less than 30 mg/dL, 1·11 (1·00-1·22) for 30 mg/dL to less than 50 mg/dL, and 1·31 (1·08-1·58) for 50 mg/dL or higher; respective HRs for on-statin lipoprotein(a) were 0·94 (0·81-1·10), 1·06 (0·94-1·21), and 1·43 (1·15-1·76). HRs were almost identical after further adjustment for previous cardiovascular disease, diabetes, smoking, systolic blood pressure, LDL cholesterol, and HDL cholesterol. The association of on-statin lipoprotein(a) with cardiovascular disease risk was stronger than for on-placebo lipoprotein(a) (interaction p=0·010) and was more pronounced at younger ages (interaction p=0·008) without effect-modification by any other patient-level or study-level characteristics. INTERPRETATION: In this individual-patient data meta-analysis of statin-treated patients, elevated baseline and on-statin lipoprotein(a) showed an independent approximately linear relation with cardiovascular disease risk. This study provides a rationale for testing the lipoprotein(a) lowering hypothesis in cardiovascular disease outcomes trials. FUNDING: Novartis Pharma AG.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Lipoproteína(a)/sangue , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Lipoproteína(a)/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
13.
N Engl J Med ; 379(16): 1519-1528, 2018 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-30221595

RESUMO

BACKGROUND: In the primary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, now published in the Journal, we report that the daily use of aspirin did not provide a benefit with regard to the primary end point of disability-free survival among older adults. A numerically higher rate of the secondary end point of death from any cause was observed with aspirin than with placebo. METHODS: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. Deaths were classified according to the underlying cause by adjudicators who were unaware of trial-group assignments. Hazard ratios were calculated to compare mortality between the aspirin group and the placebo group, and post hoc exploratory analyses of specific causes of death were performed. RESULTS: Of the 19,114 persons who were enrolled, 9525 were assigned to receive aspirin and 9589 to receive placebo. A total of 1052 deaths occurred during a median of 4.7 years of follow-up. The risk of death from any cause was 12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group (hazard ratio, 1.14; 95% confidence interval [CI], 1.01 to 1.29). Cancer was the major contributor to the higher mortality in the aspirin group, accounting for 1.6 excess deaths per 1000 person-years. Cancer-related death occurred in 3.1% of the participants in the aspirin group and in 2.3% of those in the placebo group (hazard ratio, 1.31; 95% CI, 1.10 to 1.56). CONCLUSIONS: Higher all-cause mortality was observed among apparently healthy older adults who received daily aspirin than among those who received placebo and was attributed primarily to cancer-related death. In the context of previous studies, this result was unexpected and should be interpreted with caution. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).


Assuntos
Aspirina/uso terapêutico , Mortalidade , Inibidores da Agregação de Plaquetas/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Austrália , Causas de Morte , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Humanos , Vida Independente , Masculino , Neoplasias/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Falha de Tratamento , Estados Unidos
14.
N Engl J Med ; 379(16): 1499-1508, 2018 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-30221596

RESUMO

BACKGROUND: Information on the use of aspirin to increase healthy independent life span in older persons is limited. Whether 5 years of daily low-dose aspirin therapy would extend disability-free life in healthy seniors is unclear. METHODS: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or physical disability. Participants were randomly assigned to receive 100 mg per day of enteric-coated aspirin or placebo orally. The primary end point was a composite of death, dementia, or persistent physical disability. Secondary end points reported in this article included the individual components of the primary end point and major hemorrhage. RESULTS: A total of 19,114 persons with a median age of 74 years were enrolled, of whom 9525 were randomly assigned to receive aspirin and 9589 to receive placebo. A total of 56.4% of the participants were women, 8.7% were nonwhite, and 11.0% reported previous regular aspirin use. The trial was terminated at a median of 4.7 years of follow-up after a determination was made that there would be no benefit with continued aspirin use with regard to the primary end point. The rate of the composite of death, dementia, or persistent physical disability was 21.5 events per 1000 person-years in the aspirin group and 21.2 per 1000 person-years in the placebo group (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11; P=0.79). The rate of adherence to the assigned intervention was 62.1% in the aspirin group and 64.1% in the placebo group in the final year of trial participation. Differences between the aspirin group and the placebo group were not substantial with regard to the secondary individual end points of death from any cause (12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group), dementia, or persistent physical disability. The rate of major hemorrhage was higher in the aspirin group than in the placebo group (3.8% vs. 2.8%; hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001). CONCLUSIONS: Aspirin use in healthy elderly persons did not prolong disability-free survival over a period of 5 years but led to a higher rate of major hemorrhage than placebo. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).


Assuntos
Aspirina/uso terapêutico , Intervalo Livre de Doença , Inibidores da Agregação de Plaquetas/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Austrália , Demência/epidemiologia , Pessoas com Deficiência/estatística & dados numéricos , Método Duplo-Cego , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Incidência , Vida Independente , Masculino , Mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Falha de Tratamento , Estados Unidos
15.
N Engl J Med ; 379(16): 1509-1518, 2018 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-30221597

RESUMO

BACKGROUND: Aspirin is a well-established therapy for the secondary prevention of cardiovascular events. However, its role in the primary prevention of cardiovascular disease is unclear, especially in older persons, who have an increased risk. METHODS: From 2010 through 2014, we enrolled community-dwelling men and women in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. The primary end point was a composite of death, dementia, or persistent physical disability; results for this end point are reported in another article in the Journal. Secondary end points included major hemorrhage and cardiovascular disease (defined as fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, or hospitalization for heart failure). RESULTS: Of the 19,114 persons who were enrolled in the trial, 9525 were assigned to receive aspirin and 9589 to receive placebo. After a median of 4.7 years of follow-up, the rate of cardiovascular disease was 10.7 events per 1000 person-years in the aspirin group and 11.3 events per 1000 person-years in the placebo group (hazard ratio, 0.95; 95% confidence interval [CI], 0.83 to 1.08). The rate of major hemorrhage was 8.6 events per 1000 person-years and 6.2 events per 1000 person-years, respectively (hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001). CONCLUSIONS: The use of low-dose aspirin as a primary prevention strategy in older adults resulted in a significantly higher risk of major hemorrhage and did not result in a significantly lower risk of cardiovascular disease than placebo. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).


Assuntos
Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Hemorragia/induzido quimicamente , Inibidores da Agregação de Plaquetas/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Austrália , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Método Duplo-Cego , Feminino , Hemorragia/epidemiologia , Humanos , Vida Independente , Masculino , Inibidores da Agregação de Plaquetas/efeitos adversos , Falha de Tratamento , Estados Unidos
16.
JCI Insight ; 3(17)2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30185661

RESUMO

BACKGROUND: Plasma lipidomic measures may enable improved prediction of cardiovascular outcomes in secondary prevention. The aim of this study is to determine the association of plasma lipidomic measurements with cardiovascular events and assess their potential to predict such events. METHODS: Plasma lipids (n = 342) were measured in a retrospective subcohort (n = 5,991) of the LIPID study. Proportional hazards regression was used to identify lipids associated with future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and cardiovascular death. Multivariable models adding lipid species to traditional risk factors were created using lipid ranking established from the Akaike information criterion within a 5-fold cross-validation framework. The results were tested on a diabetic case cohort from the ADVANCE study (n = 3,779). RESULTS: Specific ceramide species, sphingolipids, phospholipids, and neutral lipids containing omega-6 fatty acids or odd-chain fatty acids were associated with future cardiovascular events (106 species) and cardiovascular death (139 species). The addition of 7 lipid species to a base model (11 conventional risk factors) resulted in an increase in the C-statistics from 0.629 (95% CI, 0.628-0.630) to 0.654 (95% CI, 0.653-0.656) for prediction of cardiovascular events and from 0.673 (95% CI, 0.671-0.675) to 0.727 (95% CI, 0.725-0.728) for prediction of cardiovascular death. Categorical net reclassification improvements for cardiovascular events and cardiovascular death were 0.083 (95% CI, 0.081-0.086) and 0.166 (95% CI, 0.162-0.170), respectively. Evaluation on the ADVANCE case cohort demonstrated significant improvement on the base models. CONCLUSIONS: The improvement in the prediction of cardiovascular outcomes, above conventional risk factors, demonstrates the potential of plasma lipidomic profiles as biomarkers for cardiovascular risk stratification in secondary prevention. FUNDING: Bristol-Myers Squibb, the National Health and Medical Research Council of Australia (grants 211086, 358395, and 1029754), and the Operational Infrastructure Support Program of the Victorian government of Australia.


Assuntos
Doenças Cardiovasculares/etiologia , Sistema Cardiovascular/metabolismo , Metabolismo dos Lipídeos , Lipídeos/sangue , Prevenção Secundária , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/metabolismo , Estudos Retrospectivos , Fatores de Risco
17.
Circulation ; 138(7): 712-723, 2018 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-29367425

RESUMO

BACKGROUND: D-dimer, a degradation product of cross-linked fibrin, is a marker for hypercoagulability and thrombotic events. Moderately elevated levels of D-dimer are associated with the risk of venous and arterial events in patients with vascular disease. We assessed the role of D-dimer levels in predicting long-term vascular outcomes, cause-specific mortality, and new cancers in the LIPID trial (Long-Term Intervention with Pravastatin in Ischaemic Disease) in the context of other risk factors. METHODS: LIPID randomized patients to placebo or pravastatin 40 mg/d 5 to 38 months after myocardial infarction or unstable angina. D-dimer levels were measured at baseline and at 1 year. Median follow-up was 6.0 years during the trial and 16 years in total. RESULTS: Baseline D-dimer levels for 7863 patients were grouped by quartile (≤112, 112-173, 173-273, >273 ng/mL). Higher levels were associated with older age, female sex, history of hypertension, poor renal function, and elevated levels of B-natriuretic peptide, high-sensitivity C-reactive protein, and sensitive troponin I (each P<0.001). During the first 6 years, after adjustment for up to 30 additional risk factors, higher D-dimer was associated with a significantly increased risk of a major coronary event (quartile 4 versus 1: hazard ratio [HR], 1.45; 95% confidence interval, 1.21-1.74), major cardiovascular disease (CVD) event (HR, 1.45; 95% confidence interval, 1.23-1.71) and venous thromboembolism (HR, 4.03; 95% confidence interval, 2.31-7.03; each P<0.001). During the 16 years overall, higher D-dimer was an independent predictor of all-cause mortality (HR, 1.59), CVD mortality (HR, 1.61), cancer mortality (HR, 1.54), and non-CVD noncancer mortality (HR, 1.57; each P<0.001), remaining significant for deaths resulting from each cause occurring beyond 10 years of follow-up (each P≤0.01). Higher D-dimer also independently predicted an increase in cancer incidence (HR, 1.16; P=0.02).The D-dimer level increased the net reclassification index for all-cause mortality by 4.0 and venous thromboembolism by 13.6. CONCLUSIONS: D-dimer levels predict long-term risk of arterial and venous events, CVD mortality, and non-CVD noncancer mortality independent of other risk factors. D-dimer is also a significant predictor of cancer incidence and mortality. These results support an association of D-dimer with fatal events across multiple diseases and demonstrate that this link extends beyond 10 years' follow-up.


Assuntos
Doença das Coronárias/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Neoplasias/sangue , Tromboembolia Venosa/sangue , Adulto , Idoso , Biomarcadores/sangue , Doença das Coronárias/diagnóstico , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/mortalidade , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/mortalidade , Pravastatina/uso terapêutico , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/mortalidade
18.
Kidney Blood Press Res ; 42(6): 1033-1044, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29197871

RESUMO

BACKGROUND/AIMS: Cardiac biomarkers are associated with cardiac abnormalities and adverse outcomes in dialysis patients. Our aim was to report the effect of the beta-blocker carvedilol on cardiac biomarkers in adult dialysis patients. METHODS: The Beta-Blocker to Lower Cardiovascular Dialysis Events Feasibility Study was a randomized controlled trial comparing carvedilol to placebo. Serum and plasma were collected before the run-in, then 6 and 12 months post-randomization to measure B-type Natriuretic Peptide (BNP), N-terminal BNP (NT-ProBNP), high-sensitivity cardiac troponins I (hs-TnI) and T (hs-TnT), and galectin-3. Left ventricular global longitudinal strain (GLS) was measured by echocardiography at baseline. RESULTS: Seventy-two participants were recruited of whom 49 completed the run-in and were randomized to carvedilol (n=26) or placebo (n=23). Baseline echocardiography demonstrated median (inter-quartile range) GLS of -14.27% (-16.63 to -11.93). NTproBNP and hs-TnT correlated with GLS (Spearman's rho=0.34 [p=0.018] and rho=0.28 [p=0.049], respectively). Median change scores from baseline to 12 months did not differ significantly between participants with complete biomarker data randomized to carvedilol (n=15) or placebo (n=16) for any biomarkers. CONCLUSIONS: NT-proBNP and hs-TnT were associated with GLS. However, changes in levels of the biomarkers from baseline to 12 months were not different between groups randomized to carvedilol and placebo.


Assuntos
Carbazóis/uso terapêutico , Cardiopatias/diagnóstico , Propanolaminas/uso terapêutico , Insuficiência Renal Crônica/complicações , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Biomarcadores/sangue , Carbazóis/farmacologia , Carvedilol , Feminino , Cardiopatias/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Peptídeo Natriurético Encefálico/efeitos dos fármacos , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/efeitos dos fármacos , Propanolaminas/farmacologia , Troponina T/sangue , Troponina T/efeitos dos fármacos
19.
N Engl J Med ; 377(14): 1319-1330, 2017 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-28844192

RESUMO

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).


Assuntos
Aspirina/uso terapêutico , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/uso terapêutico , Idoso , Aspirina/efeitos adversos , Aterosclerose/complicações , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/mortalidade , Método Duplo-Cego , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Rivaroxabana/efeitos adversos , Prevenção Secundária/métodos
20.
Can J Cardiol ; 33(8): 1027-1035, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28754388

RESUMO

BACKGROUND: Long-term aspirin prevents vascular events but is only modestly effective. Rivaroxaban alone or in combination with aspirin might be more effective than aspirin alone for vascular prevention in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). Rivaroxaban as well as aspirin increase upper gastrointestinal (GI) bleeding and this might be prevented by proton pump inhibitor therapy. METHODS: Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) is a double-blind superiority trial comparing rivaroxaban 2.5 mg twice daily combined with aspirin 100 mg once daily or rivaroxaban 5 mg twice daily vs aspirin 100 mg once daily for prevention of myocardial infarction, stroke, or cardiovascular death in patients with stable CAD or PAD. Patients not taking a proton pump inhibitor were also randomized, using a partial factorial design, to pantoprazole 40 mg once daily or placebo. The trial was designed to have at least 90% power to detect a 20% reduction in each of the rivaroxaban treatment arms compared with aspirin and to detect a 50% reduction in upper GI complications with pantoprazole compared with placebo. RESULTS: Between February 2013 and May 2016, we recruited 27,395 participants from 602 centres in 33 countries; 17,598 participants were included in the pantoprazole vs placebo comparison. At baseline, the mean age was 68.2 years, 22.0% were female, 90.6% had CAD, and 27.3% had PAD. CONCLUSIONS: COMPASS will provide information on the efficacy and safety of rivaroxaban, alone or in combination with aspirin, in the long-term management of patients with stable CAD or PAD, and on the efficacy and safety of pantoprazole in preventing upper GI complications in patients receiving antithrombotic therapy.


Assuntos
Anticoagulantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Terapia Trombolítica/normas , Humanos
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