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BACKGROUND: Patients treated with antithrombotic drugs are at risk of bleeding. Bleeding may be the first manifestation of underlying cancer. METHODS: We examined new cancers diagnosed in relation to gastrointestinal or genitourinary bleeding among patients enrolled in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) and determined the hazard of new cancer diagnosis after bleeding at these sites. RESULTS: Of 27 395 patients enrolled (mean age, 68 years; women, 21%), 2678 (9.8%) experienced any (major or minor) bleeding, 713 (2.6%) experienced major bleeding, and 1084 (4.0%) were diagnosed with cancer during a mean follow-up of 23 months. Among 2678 who experienced bleeding, 257 (9.9%) were subsequently diagnosed with cancer. Gastrointestinal bleeding was associated with a 20-fold higher hazard of new gastrointestinal cancer diagnosis (7.4% versus 0.5%; hazard ratio [HR], 20.6 [95% CI, 15.2-27.8]) and 1.7-fold higher hazard of new nongastrointestinal cancer diagnosis (3.8% versus 3.1%; HR, 1.70 [95% CI, 1.20-2.40]). Genitourinary bleeding was associated with a 32-fold higher hazard of new genitourinary cancer diagnosis (15.8% versus 0.8%; HR, 32.5 [95% CI, 24.7-42.9]), and urinary bleeding was associated with a 98-fold higher hazard of new urinary cancer diagnosis (14.2% versus 0.2%; HR, 98.5; 95% CI, 68.0-142.7). Nongastrointestinal, nongenitourinary bleeding was associated with a 3-fold higher hazard of nongastrointestinal, nongenitourinary cancers (4.4% versus 1.9%; HR, 3.02 [95% CI, 2.32-3.91]). CONCLUSIONS: In patients with atherosclerosis treated with antithrombotic drugs, any gastrointestinal or genitourinary bleeding was associated with higher rates of new cancer diagnosis. Any gastrointestinal or genitourinary bleeding should prompt investigation for cancers at these sites. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.
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Aterosclerose/tratamento farmacológico , Hemorragia Gastrointestinal/induzido quimicamente , Neoplasias/diagnóstico , Rivaroxabana/uso terapêutico , Idoso , Aspirina/uso terapêutico , Aterosclerose/complicações , Doença da Artéria Coronariana/tratamento farmacológico , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
BACKGROUND AND PURPOSE: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities. METHODS: Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities. RESULTS: At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38-0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37-1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27-1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests. CONCLUSIONS: Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.
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Aspirina/uso terapêutico , Infarto Encefálico/prevenção & controle , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Idoso , Infarto Encefálico/complicações , Infarto Encefálico/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Quimioterapia Combinada , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Resultado do TratamentoAssuntos
Pantoprazol , Inibidores da Bomba de Prótons , Humanos , Pantoprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/efeitos adversos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Taxa de Filtração Glomerular/efeitos dos fármacos , Resultado do TratamentoRESUMO
Plasma Na+ concentration is regulated within narrow limits. Yet, substantial interindividual differences exist even in the normal range. The determinants of these differences are not well understood. We therefore investigated the clinical and neurohumoral associates of plasma Na+. We studied 2,364 men (age: 48 ± 12 yr) and 2,710 women (age: 47 ± 12 yr) from the prospective Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort study. In the present study, we investigated the neurohumoral factors NH2-terminal prohormone of brain natriuretic peptide (NT-proBNP) and aldosterone as volume markers and copeptin as a marker for osmoregulation. Clinical associating variables of plasma Na+ were age, sex, and plasma glucose. Furthermore, plasma Na+ levels were associated with log2 copeptin (men: standardized ß = 0.18, P < 0.001; women: standardized ß = 0.17, P < 0.001), log2 NT-proBNP (men: standardized ß = 0.07, P = 0.008; women: standardized ß = 0.12, P < 0.001), and log2 aldosterone (men: standardized ß = -0.06, P = 0.005; women: standardized ß = -0.09, P < 0.001). Copeptin and NT-proBNP showed an interaction in their association with plasma Na+. Thus, our data 1) support that osmoregulation, as estimated from copeptin levels, is a main associate of plasma Na+; 2) show a consistent association with volume markers, with higher NT-proBNP and lower aldosterone in individuals with higher plasma Na+; and 3) show that the interaction between copeptin and NT-proBNP illustrates that osmoregulation and volume regulation act in concert in the regulation of plasma Na+.
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Falência Renal Crônica/sangue , Sódio/sangue , Adulto , Fatores Etários , Idoso , Aldosterona/sangue , Aldosterona/metabolismo , Biomarcadores/sangue , Glicemia/metabolismo , Estudos de Coortes , Feminino , Seguimentos , Glicopeptídeos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Equilíbrio HidroeletrolíticoAssuntos
Aterosclerose , Doença Arterial Periférica , Tromboembolia Venosa , Aspirina/uso terapêutico , Aterosclerose/tratamento farmacológico , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Humanos , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controleRESUMO
BACKGROUND: In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown. We therefore studied the effects of dietary sodium restriction on BP and urinary albumin excretion (UAE) in kidney transplant recipients receiving RAAS blockade. STUDY DESIGN: Two-center randomized crossover trial. SETTING & PARTICIPANTS: Stable outpatient kidney transplant recipients with creatinine clearance > 30mL/min, BP ≥120/80mmHg, receiving stable RAAS blockade therapy. INTERVENTION: 6-week regular-sodium diet (target, 150mmol/24 h) and a 6-week low-sodium diet (target, 50mmol/24 h). OUTCOMES & MEASUREMENTS: Main outcome parameters were systolic and diastolic BP, UAE, and estimated glomerular filtration rate (eGFR) at the end of each diet period. Dietary adherence was assessed by 24-hour urinary sodium excretion. RESULTS: We randomly assigned 23 kidney transplant recipients, of whom 22 (mean age, 58±8 [SD] years; 50% men; mean eGFR, 51±21mL/min/1.73m(2)) completed the study. One patient withdrew from the study because of concerns regarding orthostatic hypotension on the low-sodium diet. Sodium excretion decreased from 164±50mmol/24 h during the regular-sodium diet to 87±55mmol/24 h during the low-sodium diet (mean difference, -77 [95% CI, -110 to -44] mmol/24 h; P<0.001). Sodium restriction significantly reduced systolic BP from 140±14 to 129±12mmHg (mean difference, -11 [95% CI, -14 to -7] mmHg; P<0.001), diastolic BP from 86±8 to 79±8mmHg (mean difference, -7 [95% CI, -10 to -5] mmHg; P<0.001). We found no significant effect on natural log (ln)-transformed UAE (mean difference, -0.03 [95% CI, -0.6 to 0.6] ln(mg/24 h); P=0.9) or eGFR. LIMITATIONS: No hard end points; small study; small proportion of patients willing to test the intervention; adherence to sodium diet was achieved in 86% of patients. CONCLUSIONS: In stable kidney transplant recipients receiving RAAS blockade, dietary sodium restriction effectively reduces BP without affecting eGFR. Dietary sodium restriction is relevant to BP management in kidney transplant recipients receiving RAAS blockade.
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Albuminúria/urina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pressão Sanguínea , Dieta Hipossódica , Transplante de Rim , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Anticoagulant thromboprophylaxis with low molecular weight heparin is widely used in nonsurgical settings. To obtain best estimates of the effects of nadroparin for the prevention of venous thromboembolism (VTE) in nonsurgical patients, we conducted a systematic review and meta-analysis. Data sources were Medline, Embase, and Cochrane Library supplemented with conference abstracts, without language restrictions. Selection criteria were randomized controlled trials with nadroparin at prophylactic dose in adult nonsurgical patients. Main efficacy outcomes were major VTE (the composite of symptomatic deep vein thrombosis, symptomatic pulmonary embolism, asymptomatic proximal deep vein thrombosis and VTE-related death) and symptomatic VTE. The main safety outcome was major bleeding. We expressed treatment effects as risk ratios. Ten studies (4 vs. placebo or no treatment, 4 vs. UFH, 1 vs. fondaparinux and 1 vs. warfarin) enrolling a total of 7658 patients were included. In comparison with placebo, nadroparin reduced major VTE by about one-half (RR 0.48, 95% CI 0.24-0.97) with a consistent effect on symptomatic VTE (RR 0.69, 95% CI 0.46-1.05) and no increase in major bleeding (RR 1.51, 95% CI 0.40-5.79). In comparison with other pharmacological prophylaxis, nadroparin was similarly efficacious for prevention of major VTE (RR 1.14, 95% CI 0.63-2.10) and symptomatic VTE (RR 1.10, 95% CI 0.51-2.35) and produced similar effects on major bleeding (RR 0.60, 95% CI 0.25-1.50). Five studies were open label, and for three of these the adjudication method was not described or not blinded. In nonsurgical populations at risk of VTE, nadroparin reduced VTE by about one half compared with placebo or no treatment and appeared similarly effective and safe as other prophylactic anticoagulants.
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Nadroparina/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Anticoagulantes/uso terapêutico , Humanos , Nadroparina/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Tromboembolia Venosa/prevenção & controleRESUMO
BACKGROUND: Intraocular pressure (IOP) monitoring in glaucoma management is evolving with novel devices. We investigated the reproducibility of 24 hour profiles on two consecutive days and after 30 days of self-measurements via telemetric IOP monitoring. METHODS: Seven primary patients with open-angle glaucoma previously implanted with a telemetric IOP sensor in one eye underwent automatic measurements throughout 24 hours on two consecutive days ('day 1' and 'day 2'). Patients wore an antenna adjacent to the study eye connected to a reader device to record IOP every 5 min. Also, self-measurements in six of seven patients were collected for a period of 30 days. Analysis included calculation of hourly averages to correlate time-pairs of day 1 versus day 2 and the self-measurements vers day 2. RESULTS: The number of IOP measurements per patient ranged between 151 and 268 on day 1, 175 and 268 on day 2 and 19 and 1236 during 30 days of self-measurements. IOP time-pairs of automatic measurements on day 1 and day 2 were significantly correlated at the group level (R=0.83, p<0.001) and in four individual patients (1, 2, 6 and 7). IOP time-pairs of self-measurements and day 2 were significantly correlated at the group level (R=0.4, p<0.001) and in four individual patients (2, 5, 6 and 7). CONCLUSIONS: Twenty-four hour automatic measurements of IOP are correlated on consecutive days and, though to a lesser degree, with self-measurements. Therefore a virtual 24-hour IOP curve might be constructed from self-measurements. Both options provide an alternative to frequent in-office IOP measurements.
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BACKGROUND: Win ratio (WR) is a newer analytic approach for trials with composite end points that accounts for the relative importance of individual components. Our objective was to compare the results of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial analyzed using WR with those obtained using conventional statistical approaches. METHODS: We used an unmatched WR analysis for first and total (first plus recurrent) events to examine effects of rivaroxaban with aspirin and rivaroxaban alone vs aspirin alone on primary efficacy (cardiovascular death, stroke, myocardial infarction), safety (modified International Society on Thrombosis and Haemostasis major bleeding), and net clinical benefit (primary efficacy plus fatal or critical organ bleeding) end points. We compared the WR results with those obtained using the Cox proportional hazards regression model for first events and Anderson-Gill method for total events. We calculated the win difference to estimate absolute treatment effects. RESULTS: The WR approach produced results consistent with those obtained using conventional statistical methods for the primary composite end point (first event: WR, 1.32 [95% confidence interval (CI), 1.14-1.52]; 1/Cox hazard ratio, 1.32 [95% CI, 1.16-1.52]; total [first plus recurrent] events: WR, 1.32 [95% CI, 1.14-1.52]; 1/Anderson-Gill hazard ratio, 1.32 [95% CI, 1.16-1.54]) as well as for main safety and net clinical benefit end points. The absolute benefits of the combination of rivaroxaban and aspirin compared with aspirin alone calculated using the win difference were greatest in those with multiple high-risk features. CONCLUSIONS: Reanalysis of the COMPASS trial results using WR produced results that were consistent with those obtained using conventional statistical approaches. CLINICAL TRIAL REGISTRATION: NCT01776424.
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Background: Dabigatran is effective and safe for stroke prevention in patients with atrial fibrillation and for venous thromboembolism prevention and treatment. In Canada, APO-dabigatran, a generic formulation, has been approved based on a bioequivalence study, but its bioavailability in settings of reduced gastric acidity has not been examined. Methods: Treatment With APO-Dabigatran Absorption (TADA) was an open-label crossover study in 46 healthy male volunteers, comparing the absorption of APO-dabigatran (150 mg) with vs without rabeprazole. The primary outcome was the 24-hour total dabigatran exposure as measured by area under the curve (AUC) and peak concentration (Cmax). Results: Compared with no rabeprazole pretreatment, the total dabigatran AUC (geometric mean [gmean] AUC0-tz: 567.2 vs 804 ngh/mL, and gmean AUC0-∞: 609.7 vs 804) and Cmax (gmean: 64.1 vs 104.4 ng/mL) were significantly reduced with rabeprazole. The percent gmean ratios for AUC0-tz, AUC0-∞, and Cmax (with rabeprazole vs without) were 70.5% (95% confidence interval [CI]: 51.9% to 95.7%), 71.8% (95% CI: 53.1% to 96.9%), and 61.4% (95% CI: 44.1% to 85.5%), respectively. With rabeprazole, the proportions of participants with > 50% reduction in AUC0-tz, AUC0-∞, and Cmax were 32.6%, 30.4%, and 39.1%, respectively. Conclusions: When APO-dabigatran is administered with rabeprazole, the exposure to dabigatran is reduced by about 30%, which is similar to the level observed with Pradaxa when it was co-administered with a proton pump inhibitor. However, the finding that one-third of participants had a > 50% reduction in exposure is concerning, and it highlights the need for caution in patients who have, or are at risk of, reduced gastric acidity.
Contexte: Le dabigatran est une option thérapeutique sûre et efficace pour prévenir les accidents vasculaires cérébraux chez les patients atteints de fibrillation auriculaire et pour prévenir et traiter les thromboembolies veineuses. Au Canada, APO-dabigatran (une version générique) a été homologué sur la base d'une étude de bioéquivalence, mais sa biodisponibilité en contexte d'acidité gastrique réduite n'a pas été évaluée. Méthodologie: L'étude TADA ( T reatment with A PO- D abigatran A bsorption) est une étude croisée menée en mode ouvert auprès de 46 hommes volontaires en bonne santé, afin de comparer l'absorption d'APO-dabigatran (à 150 mg) avec et sans rabéprazole. Le critère d'évaluation principal était l'exposition totale sur 24 heures au dabigatran, telle que mesurée par la surface sous la courbe (SSC) et la concentration maximale (Cmax). Résultats: Par rapport à une administration sans prétraitement par rabéprazole, une réduction significative de la SSC totale du dabigatran (moyenne géométrique [MG] SSC0-tz : 567,2 par rapport à 804 ngh/ml; MG SSC0-∞ : 609,7 par rapport à 804 ngh/ml) et de la Cmax (MG : 64,1 par rapport à 104,4 ng/ml) a été observée avec la prise de rabéprazole. Les ratios des MG en pourcentage de la SSC0-tz, de la SSC0-∞, et de la Cmax (avec et sans rabéprazole) étaient de 70,5 % (intervalle de confiance [IC] à 95 % : 51,9 % à 95,7 %), 71,8 % (IC à 95 % : 53,1 % à 96,9 %) et 61,4 % (IC à 95 % : 44,1 % à 85,5 %), respectivement. Les proportions de participants chez qui une réduction de > 50 % de la SSC0-tz, de la SSC0-∞ ou de la Cmax a été notée avec l'administration du rabéprazole s'élevaient à 32,6 %, 30,4 % et 39,1 %, respectivement. Conclusions: Lors de l'administration d'APO-dabigatran en concomitance avec le rabéprazole, l'exposition au dabigatran était réduite d'environ 30 %, une valeur comparable à la réduction observée lors de l'administration de Pradaxa en concomitance avec un inhibiteur de la pompe à protons. La réduction de > 50 % de l'exposition médicamenteuse chez le tiers des participants n'en est pas moins préoccupante et démontre la nécessité de faire preuve de prudence lorsque l'acidité gastrique est réduite ou risque d'être réduite chez un patient.
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Importance: Vascular risk factors are associated with cognitive decline but studies addressing individual risk factors have not demonstrated an effect of risk factor management on the preservation of cognition. Few trials have examined the effect of vascular risk factor management on function. Objective: To determine if a polypill could reduce cognitive and functional decline in people with risk factors but without manifest cardiovascular disease. Design, Setting, and Participants: The International Polycap Study 3 (TIPS-3) was a 2 × 2 × 2 factorial randomized clinical trial. Hospital and community-based centers in 8 countries recruited and followed up participants between July 30, 2012, and September 30, 2020. A total of 5713 individuals were randomly assigned to treatment groups, and 2098 people 65 years or older at intermediate risk of cardiovascular disease completed a cognitive assessment and were included in the analyses. Interventions: Polypill (antihypertensives and a statin), aspirin, or a combination of both treatments. Main Outcomes and Measures: Cognitive and functional assessments completed at baseline, 2 years, and study end. The primary outcome was the effect of a polypill compared with placebo and a polypill plus aspirin compared with double placebo on the composite outcome of the proportion of participants in each group who experienced a substantive decrease (>1.5 SD change) in cognitive or functional abilities. Results: Of the 2389 study participants older than 65 years, a total of 2098 (88%; mean [SD] age, 70.1 [4.5] years; 1266 female individuals [60%]) completed the baseline and follow-up assessment. A total of 1796 participants (86%) had hypertension, and 680 participants (32%) had impaired fasting plasma glucose levels. Mean (SD) baseline systolic blood pressure was 146.1 (17.7) mm Hg, and mean (SD) low-density lipoprotein cholesterol (LDL-C) level was 124.3 (40.7) mg/dL and decreased by 5.7 mm Hg and 24 mg/dL, respectively, among those assigned to the polypill group. During a 5-year follow-up, there were no significant differences between treatment groups in the number of participants who experienced substantive cognitive decline (356 assigned polypill, 328 assigned placebo) or dementia (2 assigned polypill, 4 assigned placebo). Functional decline was reduced during follow-up for those assigned to polypill compared with placebo (mean [SD] country-standardized adjusted follow-up Standard Assessment of Global Everyday Activities [SAGEA] scores, 0.06 [0.03] vs 0.15 [0.03]; P = .01) and polypill plus aspirin compared with double placebo (mean [SD] country-standardized adjusted follow-up SAGEA scores, 0.01 [0.04] vs 0.14 [0.04]; P = .01). Conclusions and Relevance: In this randomized clinical trial of patients 65 years or older with vascular risk factors, a polypill, with or without aspirin, was not associated with reduced cognitive outcomes but was associated with reduced functional decline.
Assuntos
Aspirina , Doenças Cardiovasculares , Humanos , Feminino , Idoso , Aspirina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Hidroclorotiazida/uso terapêutico , Combinação de Medicamentos , CogniçãoRESUMO
BACKGROUND: Patients with glaucoma on topical glaucoma medication are often affected by dry eye symptoms and thus likely to rub or squeeze their eyelids. Here, we telemetrically measure peak intraocular pressure (IOP) during eyelid manoeuvres and eyelid rubbing. METHODS: Eleven patients with primary open-angle glaucoma (POAG) previously implanted with a telemetric IOP sensor (Eyemate-IO) were instructed to look straight ahead for 1 min as a baseline measurement. Next, 6 repeats of blinking on instruction with 10 s intervals in between were performed. In addition, 5 repeats of eyelid closure (n=9), eyelid squeezing and eyelid rubbing (n=7) were performed with 15 s intervals in between. IOP was recorded via an external antenna placed around the study eye. Average peak IOP increases from baseline were analysed and tested against zero (no change) with one-sample t-tests. RESULTS: For eyelid rubbing, the average peak ∆ IOP increase (mean±SEM) was 59.1±9.6 mm Hg (p<0.001) from baseline. It was 42.2±5.8 mm Hg (p<0.0001) for eyelid squeezing, 3.8±0.6 mm Hg (n=9, p<0.01) for eyelid closure and 11.6±2.4 mm Hg (p<0.001) for voluntary blinking. No IOP change except for a short irregularity in the ocular pulse was observed during involuntary blinking. CONCLUSION: Eyelid manoeuvres in patients with POAG elicited brief increases in IOP that were particularly large with squeezing and rubbing. Further investigation of the potential implications for glaucoma progression is warranted.
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Glaucoma de Ângulo Aberto , Glaucoma , Humanos , Pressão Intraocular , Glaucoma de Ângulo Aberto/diagnóstico , Tonometria Ocular , Glaucoma/diagnóstico , Pálpebras , Músculos OculomotoresRESUMO
Background: Bleeding is the most common adverse event in those with cardiovascular (CV) disease receiving antithrombotic therapy, and it most commonly occurs in the gastrointestinal (GI) tract. Clinicians often dismiss bleeding as an adverse event that is reversible with effective antithrombotic therapy, but bleeding is associated with substantial morbidity and mortality, most likely mediated through an increased risk of CV events. Reducing the burden of bleeding requires knowledge of the potentially modifiable risk factors for bleeding and the potentially modifiable risk factors for adverse outcomes after bleeding. Methods: INTERBLEED is an international, multicentre, 2-component, observational study, with an incident case-control study examining the risk factors for GI bleeding, and a prospective cohort study of risk factors for CV events after GI bleeding. Cases either have CV disease and present to the hospital with GI bleeding or develop GI bleeding during hospitalization. Controls have CV disease, but no history of GI bleeding. We use a questionnaire to obtain detailed information on known and potential risk factors for GI bleeding and for CV events and outcomes after bleeding. We obtain CV and anthropometric measurements, perform functional and cognitive assessments, and follow participants at 3 months and 12 months. Results: As of April 1, 2022, the study is ongoing in 10 countries at 31 centres and has recruited 2407 cases and 1478 controls. Conclusions: Knowledge of risk factors for bleeding, and risk factors for CV events and functional decline after bleeding, will help develop strategies to prevent bleeding and subsequent complications.
Contexte: L'hémorragie est l'effet indésirable le plus fréquent chez les patients atteints de maladies cardiovasculaires (CV) qui reçoivent un traitement antithrombotique, et elle survient le plus souvent dans le tractus gastro-intestinal (GI). Les cliniciens considèrent souvent l'hémorragie comme une simple manifestation indésirable réversible par un traitement antithrombotique efficace, mais une morbidité et une mortalité considérables y sont associées, probablement en raison d'un risque accru d'événements CV. Une réduction du fardeau de l'hémorragie nécessite une connaissance des facteurs de risque potentiellement modifiables tant de l'hémorragie que des événements indésirables qui surviennent après l'hémorragie. Méthodologie: INTERBLEED est une étude internationale, observationnelle et multicentrique à deux volets; le premier volet est une étude cas-témoins incidents visant à examiner les facteurs de risque d'hémorragie GI, alors que le second volet est une étude de cohorte prospective visant à examiner les facteurs de risque d'événements CV après une hémorragie GI. Les cas sont des patients atteints de maladies CV qui consultent les services hospitaliers pour une hémorragie GI ou qui présentent une hémorragie GI en cours d'hospitalisation. Les témoins sont des patients atteints de maladies CV, mais sans antécédents d'hémorragie GI. Un questionnaire est utilisé pour obtenir des renseignements détaillés au sujet de facteurs de risque connus et potentiels d'hémorragie GI et d'événements CV et d'autres résultats de santé après une hémorragie. Des mesures cardiovasculaires et anthropométriques ainsi que des évaluations fonctionnelles et cognitives sont réalisées, et les participants sont revus après trois mois et 12 mois. Résultats: En date du 1er avril 2022, l'étude est en cours dans 10 pays et 31 établissements de santé; 2 407 cas et 1 478 témoins ont été recrutés. Conclusions: La connaissance des facteurs de risque d'hémorragie, ainsi que des facteurs de risque d'événements CV et de déclin fonctionnel à la suite d'une hémorragie, aidera à mettre en place des stratégies pour prévenir les hémorragies et les complications qui peuvent en découler.
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AIMS: To describe outcomes of patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD) enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) randomized trial who were treated with the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily during long-term open-label extension (LTOLE). METHODS AND RESULTS: Of the 27 395 patients enrolled in COMPASS, 12 964 (mean age at baseline 67.2 years) from 455 sites in 32 countries were enrolled in LTOLE and treated with the combination of rivaroxaban and aspirin for a median of 374 additional days (range 1-1191 days). During LTOLE, the incident events per 100 patient years were as follows: for the primary outcome [cardiovascular death, stroke, or myocardial infarction (MI)] 2.35 [95% confidence interval (CI) 2.11-2.61], mortality 1.87 (1.65-2.10), stroke 0.62 (0.50-0.76), and MI 1.02 (0.86-1.19), with CIs that overlapped those seen during the randomized treatment phase with the combination of rivaroxaban and aspirin. The incidence rates for major and minor bleeding were 1.01 (0.86-1.19) and 2.49 (2.24-2.75), compared with 1.67 (1.48-1.87) and 5.11 (95% CI 4.77-5.47), respectively, during the randomized treatment phase with the combination. CONCLUSION: In patients with chronic CAD and/or PAD, extended combination treatment for a median of 1 year and a maximum of 3 years was associated with incidence rates for efficacy and bleeding that were similar to or lower than those seen during the randomized treatment phase, without any new safety signals.
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Infarto do Miocárdio , Doença Arterial Periférica , Acidente Vascular Cerebral , Humanos , Lactente , Aspirina , Quimioterapia Combinada , Infarto do Miocárdio/epidemiologia , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/epidemiologia , Rivaroxabana , Acidente Vascular Cerebral/epidemiologiaRESUMO
AIMS: (1) To test the feasibility of simultaneous steady-state pattern electroretinogram (ssPERG) and intraocular pressure (IOP) measurements with an implanted IOP sensor. (2) To explore the scope of this approach for detecting PERG changes during IOP manipulation in a model of lateral decubitus positioning (LDP; lateral position). METHODS: 15 healthy controls and 15 treated glaucoma patients participated in the study. 8 patients had an IOP sensor (Eyemate-IO, Implandata Ophthalmic Products GmbH) in the right eye (GLAIMP) and 7 had no sensor and with glaucoma in the left eye. (1) We compared PERGs with and without simultaneous IOP read-out in GLAIMP. (2) All participants were positioned in the following order: sitting1 (S1), right LDP (LDR), sitting2 (S2), left LDP (LDL) and sitting3 (S3). For each position, PERG amplitudes and IOP were determined with rebound tonometry (Icare TA01i) in all participants without the IOP sensor. RESULTS: Electromagnetic intrusions of IOP sensor read-out onto ssPERG recordings had, due to different frequency ranges, no relevant effect on PERG amplitudes. IOP and PERG measures were affected by LDP, for example, IOP was increased during LDR versus S1 in the lower eyes of GLAIMP and controls (5.1±0.6 mmHg, P0.025=0.00004 and 1.6±0.6 mmHg, P0.025=0.02, respectively) and PERG amplitude was reversibly decreased (-25±10%, P0.025=0.02 and -17±5%, P0.025, respectively). CONCLUSIONS: During LDP, both IOP and PERG changed predominantly in the lower eye. IOP changes induced by LDP may be a model for studying the interaction of IOP and ganglion-cell function.
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Glaucoma/fisiopatologia , Pressão Intraocular/fisiologia , Células Ganglionares da Retina/fisiologia , Telemedicina/instrumentação , Tonometria Ocular/instrumentação , Adulto , Idoso , Eletrorretinografia , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Seguimentos , Glaucoma/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Purpose: To explore the effect of gaze direction and eyelid closure on intraocular pressure (IOP). Methods: Eleven patients with primary open-angle glaucoma previously implanted with a telemetric IOP sensor were instructed to view eight equally-spaced fixation targets each at three eccentricities (10°, 20°, and 25°). Nine patients also performed eyelid closure. IOP was recorded via an external antenna placed around the study eye. Differences of mean IOP between consecutive gaze positions were calculated. Furthermore, the effect of eyelid closure on gaze-dependent IOP was assessed. Results: The maximum IOP increase was observed at 25° superior gaze (mean ± SD: 4.4 ± 4.9 mm Hg) and maximum decrease at 25° inferonasal gaze (-1.6 ± 0.8 mm Hg). There was a significant interaction between gaze direction and eccentricity (P = 0.003). Post-hoc tests confirmed significant decreases inferonasally for all eccentricities (mean ± SEM: 10°: -0.7 ± 0.2, P = 0.007; 20°: -1.1 ± 0.2, P = 0.006; and 25°: -1.6 ± 0.2, P = 0.006). Eight of 11 eyes showed significant IOP differences between superior and inferonasal gaze at 25°. IOP decreased during eyelid closure, which was significantly lower than downgaze at 25° (mean ± SEM: -2.1 ± 0.3 mm Hg vs. -0.7 ± 0.2 mm Hg, P = 0.014). Conclusions: Our data suggest that IOP varies reproducibly with gaze direction, albeit with patient variability. IOP generally increased in upgaze but decreased in inferonasal gaze and on eyelid closure. Future studies should investigate the patient variability and IOP dynamics.
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Técnicas Biossensoriais/instrumentação , Pálpebras/fisiologia , Fixação Ocular/fisiologia , Glaucoma de Ângulo Aberto/diagnóstico , Pressão Intraocular/fisiologia , Telemetria/métodos , Tonometria Ocular/instrumentação , Idoso , Eletrodos Implantados , Desenho de Equipamento , Feminino , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
In the general population we recently reported a consistent association between plasma sodium and volume markers, suggesting that individuals with higher plasma sodium have higher extracellular fluid volume (ECFV). To test this hypothesis, we analyzed the association between plasma sodium and directly measured ECFV (iothalamate distribution volume) in healthy men. Second, we studied whether plasma sodium is associated with blood pressure. We analyzed data from 70 men (age 24 ± 7 years) at the end of two 7-day periods on a low-sodium diet (LS, 50 mmol Na/24 h) and a high-sodium diet (HS, 200 mmol Na/24 h), respectively. The association of plasma sodium with blood pressure was assessed in the combined data of the different sodium intakes by linear mixed effects models. A positive univariable association between plasma sodium and ECFV was found during HS (ß = 0.24, p = 0.042) and LS (ß = 0.23, p = 0.058), respectively. Individual values of plasma sodium on LS and HS diet were strongly correlated (ß = 0.68, p < 0.001), as were values for ECFV (ß = 0.54, p < 0.001). In the combined data set plasma sodium level was significantly associated with ECFV (B [SE] = 0.10 [0.04], p = 0.02), and systolic blood pressure (SBP, B [SE] = 0.73 [0.26], p = 0.006), independent of ECFV. In conclusion, plasma sodium concentration is positively associated with ECFV on both LS and HS intake. Our data confirm and extend prior data on individual regulation of plasma sodium and suggest that this is associated with individuality of the regulation of ECFV. Finally, plasma sodium level is associated with SBP, independent of ECFV and diet.
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Pressão Sanguínea/fisiologia , Líquido Extracelular/metabolismo , Sódio na Dieta/administração & dosagem , Sódio na Dieta/sangue , Sódio/sangue , Adolescente , Adulto , Pressão Sanguínea/efeitos dos fármacos , Líquido Extracelular/efeitos dos fármacos , Voluntários Saudáveis , Humanos , Masculino , Distribuição Aleatória , Adulto JovemRESUMO
OBJECTIVE: In patients with chronic coronary or peripheral artery disease enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies trial, randomised antithrombotic treatments were stopped after a median follow-up of 23 months because of benefits of the combination of rivaroxaban 2.5 mg two times per day and aspirin 100 mg once daily compared with aspirin 100 mg once daily. We assessed the effect of switching to non-study aspirin at the time of early stopping. METHODS: Incident composite of myocardial infarction, stroke or cardiovascular death was estimated per 100 person-years (py) during randomised treatment (n=18 278) and after study treatment discontinuation to non-study aspirin (n=14 068). RESULTS: During randomised treatment, the combination compared with aspirin reduced the composite (2.2 vs 2.9/100 py, HR: 0.76, 95% CI 0.66 to 0.86), stroke (0.5 vs 0.8/100 py, HR: 0.58, 95% CI 0.44 to 0.76) and cardiovascular death (0.9 vs 1.2/100 py, HR: 0.78, 95% CI 0.64 to 0.96). During 1.02 years after early stopping, participants originally randomised to the combination compared with those randomised to aspirin had similar rates of the composite (2.1 vs 2.0/100 py, HR: 1.08, 95% CI 0.84 to 1.39) and cardiovascular death (1.0 vs 0.8/100 py, HR: 1.26, 95% CI 0.85 to 1.86) but higher stroke rate (0.7 vs 0.4/100 py, HR: 1.74, 95% CI 1.05 to 2.87) including a significant increase in ischaemic stroke during the first 6 months after switching to non-study aspirin. CONCLUSION: Discontinuing study rivaroxaban and aspirin to non-study aspirin was associated with the loss of cardiovascular benefits and a stroke excess. TRIAL REGISTRATION NUMBER: NCT01776424.
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Aspirina , Doença das Coronárias , AVC Isquêmico , Infarto do Miocárdio , Doença Arterial Periférica , Rivaroxabana , Suspensão de Tratamento/estatística & dados numéricos , Idoso , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Doença das Coronárias/diagnóstico , Doença das Coronárias/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Substituição de Medicamentos/efeitos adversos , Quimioterapia Combinada/métodos , Duração da Terapia , Feminino , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Humanos , AVC Isquêmico/etiologia , AVC Isquêmico/mortalidade , AVC Isquêmico/prevenção & controle , Masculino , Mortalidade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Avaliação de Processos e Resultados em Cuidados de Saúde , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/tratamento farmacológico , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversosRESUMO
BACKGROUND: The combination of 2.5 mg rivaroxaban twice daily and 100 mg aspirin once daily compared with 100 mg aspirin once daily reduces major adverse cardiovascular (CV) events in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD). OBJECTIVES: The aim of this work was to report the effects of the combination on overall and cause-specific mortality. METHODS: The COMPASS trial enrolled 27,395 patients of whom 18,278 were randomized to the combination (n = 9,152) or aspirin alone (n = 9,126). Deaths were adjudicated by a committee blinded to treatment allocation. Previously identified high-risk baseline features were polyvascular disease, chronic kidney disease, mild or moderate heart failure, and diabetes. RESULTS: During a median of 23 months of follow-up (maximum 47 months), 313 patients (3.4%) allocated to the combination and 378 patients (4.1%) allocated to aspirin alone died (hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.71-0.96; P = 0.01). Compared with aspirin, the combination reduced CV death (160 [1.7%] vs 203 [2.2%]; HR: 0.78; 95% CI: 0.64-0.96; P = 0.02) but not non-CV death. There were fewer deaths following MI, stroke, and CV procedures, as well as fewer sudden cardiac, other, and unknown causes of CV deaths and coronary heart disease deaths. Patients with 0, 1, 2, and 3 or 4 high-risk features at baseline had 4.2, 4.8, 25.0, and 53.9 fewer deaths, respectively, per 1000 patients treated for 30 months. CONCLUSIONS: The combination of rivaroxaban and aspirin compared with aspirin reduced overall and CV mortality with consistent reductions in cause specific CV mortality in patients with chronic CAD or PAD. The absolute mortality benefits are greater with increasing baseline risk. (Cardiovascular Outcomes for People Using Anticoagulant Strategies [COMPASS]; NCT01776424).