LUCIANO FERREIRA DRAGER
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/63, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/63, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Effects of continuous positive airway pressure on depression and anxiety symptoms in patients with obstructive sleep apnoea: results from the sleep apnoea cardiovascular Endpoint randomised trial and meta-analysis(2019) ZHENG, Danni; XU, Ying; YOU, Shoujiang; HACKETT, Maree L.; WOODMAN, Richard J.; LI, Qiang; WOODWARD, Mark; LOFFLER, Kelly A.; RODGERS, Anthony; DRAGER, Luciano F.; LORENZI-FILHO, Geraldo; WANG, Xia; QUAN, Wei Wei; TRIPATHI, Manjari; MEDIANO, Olga; OU, Qiong; CHEN, Rui; LIU, Zhihong; ZHANG, Xilong; LUO, Yuanming; MCARDLE, Nigel; MUKHERJEE, Sutapa; MCEVOY, R. Douglas; ANDERSON, Craig S.Background: Whether continuous positive airway pressure (CPAP) treatment can improve depression or anxiety symptoms in obstructive sleep apnoea (OSA) patients remains uncertain. Methods: Secondary analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, combined with a systematic review of randomised evidence. The SAVE secondary analyses involved 2410 patients with co-existing moderate-severe OSA and established cardiovascular disease randomly allocated to CPAP treatment plus usual care or usual care alone and followed up for 3.7 (SD 1.6) years. We evaluated the effect of CPAP treatment on depression and anxiety caseness (scores >= 8 on the Hospital Anxiety and Depression Scale depression and anxiety subscales [HADS-D and HADS-A]) for OSA patients. Findings: CPAP treatment was associated with reduced odds of depression caseness (adjusted odds ratio [OR] 0.80, 95% confidence interval [CI] 0.65-0.98, P=0.031) compared to usual care in the SAVE trial and the treatment effect was greater in those with pre-existing depression symptoms. A systematic review of 20 randomised trials including 4255 participants confirmed a benefit of CPAP in reducing depression symptoms in OSA patients: the overall effect (standardised mean difference) was -0.18 (95% CI -0.24 to -0.12). No effect of CPAP treatment on anxiety caseness was found both in patients of the SAVE study (adjusted OR 0.98, 95% CI 0.78-1.24, P = 0.89) and the systematic review. Interpretation: CPAP reduces depression symptoms in patients with co-existing OSA and CVD independently of improvements in sleepiness. (C) 2019 Published by Elsevier Ltd.
- Effect of Continuous Positive Airway Pressure on Weight and Local Adiposity in Adults with Obstructive Sleep Apnea A Meta-Analysis(2021) CHEN, Baixin; DRAGER, Luciano F.; PEKER, Yuksel; VGONTZAS, Alexandros N.; PHILLIPS, Craig L.; HOYOS, Camilla M.; SALLES, Gil F.; GUO, Miaolan; LI, YunRationale: Evidence suggests that continuous positive airway pressure (CPAP) treatment promotes weight gain in patients with obstructive sleep apnea (OSA). It is unclear whether weight gain is influenced by CPAP adherence or comorbid disorders. Objectives: To examine the CPAP effects on body mass index (BMI) and local adiposity and the potential moderators of CPAP effects on BMI in patients with OSA. Methods: We searched PubMed/Medline, Embase, and Cochrane through December 2019. Randomized controlled trials of CPAP versus control treatment with >4 weeks' treatment were included. Results: A total of 39 randomized controlled trials with 6,954 subjects were included. In intention-to-treat analysis, the BMI increased significantly after CPAP treatment compared with control treatment (weighted mean difference [WMD], 0.148 kg/m(2); 95% confidence interval, 0.04-0.26; P = 0.001). In studies demonstrating an increase in the BMI, waist and neck circumferences were also significantly increased. Subgroup analyses revealed that an increased BMI was attributable to CPAP use of <5 h/night (WMD, 0.231) but was not attributable to CPAP use of.5 h/night (WMD, 0.001; between-group P value = 0.049). Furthermore, the BMI increased significantly in patients without cardiovascular disease (CVD; WMD, 0.200), whereas it decreased significantly in those with CVD at baseline (WMD, 20.188; between-group P value, 0.001). Moreover, the BMI increased significantly in patients with dysglycemia (WMD, 0.499) but did not increase in those without dysglycemia at baseline (WMD, 0.100; between-group P value = 0.032). Meta-regression confirmed the subgroup findings. Conclusions: The BMI increased significantly in patients with OSA after CPAP treatment, especially in those with CPAP use of <5 h/night, without CVD and/or with dysglycemia at baseline. CPAP use of at least 5 h/night seems to be necessary in mitigating the risk for weight gain in patients with OSA.
- Adherence with positive airway pressure therapy for obstructive sleep apnea in developing vs. developed countries: a big data study(2021) DRAGER, Luciano F.; MALHOTRA, Atul; YAN, Yang; PEPIN, Jean-Louis; ARMITSTEAD, Jeff P.; WOEHRLE, Holger; NUNEZ, Carlos M.; CISTULLI, Peter A.; V, Adam BenjafieldStudy Objectives: Minimal focus has been placed on variations in health care delivery for obstructive sleep apnea (OSA). This study compared positive airway pressure usage in developing countries (Brazil and Mexico) vs. a developed country (United States) and investigated the impact of a patient engagement tool (myAir; ResMed, San Diego, CA) on adherence. Methods: Deidentified data from the AirView database (ResMed) for patients receiving positive airway pressure therapy with wirelessly connected Air10 (AirSense and AirCurve) devices in Brazil, Mexico, and the United States were analyzed. Adherence was defined using US Center for Medicare and Medicaid Services (CMS) criteria (usage >= 4 h/night on >= 70% of nights in the first 90 days). Results: The analysis included 4,181,490 patients (Brazil: 31,672; Mexico 16,934; United States: 4,132,884). CMS adherence over 90 days was slightly lower in Latin America vs. the United States (Brazil: 71.7%; Mexico: 66.4%; United States: 74.0%). Significantly fewer patients were using the patient engagement tool in Brazil (8.1%) and Mexico (2.8%) vs. the United States (26%; both P < .001). Patients registered to use an engagement tool had a higher rate of CMS adherence and were twice as likely to achieve CMS adherence. Average daily usage and days with usage > 4 hours in the first week were the strongest predictors of CMS adherence. Across all countries, > 80% of patients meeting CMS criteria at 3 months were still using positive airway pressure therapy at 1 year, with 1-year adherences rates of > 75%. Conclusions: Short-term and long-term positive airway pressure adherence rates in Brazil and Mexico were similar to those achieved in the United States. Patients who registered to use an engagement tool consistently had better adherence than those who did not.
- OSA and cardiometabolic risk: What's the bottom line?(2017) HOYOS, Camilla M.; DRAGER, Luciano F.; PATEL, Sanjay R.Obstructive sleep apnoea (OSA) is a common condition characterized by repetitive upper airway obstruction during sleep. OSA promotes wide intrathoracic pressure swings, intermittent hypoxia and sleep fragmentation. Growing evidence derived from animal models mimicking the oxygen profile observed in patients with OSA as well as clinical studies support that this important sleep-disordered breathing is associated with increased cardiovascular risk. Although the precise mechanisms are not fully established, it is conceivable that the metabolic deregulation promoted by the components of OSA may have an important causal role in the poor cardiovascular prognosis. In this review, we summarize the potential role of OSA and its components on cardiometabolic disease. We also summarize evidence evaluating the impact of OSA treatment (notably continuous positive airway pressure) on reversing the metabolic deregulation promoted by OSA. Finally, we discuss the research agenda and perspectives for this important research area.
- Nasal vs Oronasal CPAP for OSA Treatment A Meta-Analysis(2018) ANDRADE, Rafaela G. S.; VIANA, Fernanda M.; NASCIMENTO, Juliana A.; DRAGER, Luciano F.; MOFFA, Adriano; BRUNONI, Andre R.; GENTA, Pedro R.; LORENZI-FILHO, GeraldoBACKGROUND: Nasal CPAP is the ""gold standard"" treatment for OSA. However, oronasal masks are frequently used in clinical practice. The aim of this study was to perform a meta-analysis of all randomized and nonrandomized trials that compared nasal vs oronasal masks on CPAP level, residual apnea-hypopnea index (AHI), and CPAP adherence to treat OSA. METHODS: The Cochrane Central Register of Controlled Trials, Medline, and Web of Science were searched for relevant studies in any language with the following terms: ""sleep apnea"" and ""CPAP"" or ""sleep apnea"" and ""oronasal mask"" or ""OSA"" and ""oronasal CPAP"" or ""oronasal mask"" and ""adherence."" Studies on CPAP treatment for OSA were included, based on the following criteria: (1) original article; (2) randomized or nonrandomized trials; and (3) comparison between nasal and oronasal CPAP including pressure level, and/or residual AHI, and/or CPAP adherence. RESULTS: We identified five randomized and eight nonrandomized trials (4,563 patients) that reported CPAP level and/or residual AHI and/or CPAP adherence. Overall, the random-effects meta-analysis revealed that as compared with nasal, oronasal masks were associated with a significantly higher CPAP level (Hedges' g, -0.59; 95% CI, -0.82 to -0.37; P < .001) (on average, +1.5 cm H2O), higher residual AHI (Hedges' g, -0.34; 95% CI, -0.52 to -0.17; P < .001) (+2.8 events/h), and a poorer adherence (Hedges' g, 0.50; 95% CI, 0.21-0.79; P = .001) (-48 min/night). CONCLUSIONS: Oronasal masks are associated with a higher CPAP level, higher residual AHI, and poorer adherence than nasal masks.
- Continuous Positive Airway Pressure Treatment, Glycemia, and Diabetes Risk in Obstructive Sleep Apnea and Comorbid Cardiovascular Disease(2020) LOFFLER, Kelly A.; HEELEY, Emma; FREED, Ruth; MENG, Rosie; BITTENCOURT, Lia R.; CARVALHO, Carolina C. Gonzaga; CHEN, Rui; HLAVAC, Michael; LIU, Zhihong; LORENZI-FILHO, Geraldo; LUO, Yuanming; MCARDLE, Nigel; MUKHERJEE, Sutapa; YAP, Hooi Shan; ZHANG, Xilong; PALMER, Lyle J.; ANDERSON, Craig S.; MCEVOY, R. Doug; DRAGER, Luciano F.OBJECTIVE Despite evidence of a relationship among obstructive sleep apnea (OSA), metabolic dysregulation, and diabetes, it is uncertain whether OSA treatment can improve metabolic parameters. We sought to determine effects of long-term continuous positive airway pressure (CPAP) treatment on glycemic control and diabetes risk in patients with cardiovascular disease (CVD) and OSA. RESEARCH DESIGN AND METHODS Blood, medical history, and personal data were collected in a substudy of 888 participants in the Sleep Apnea cardioVascular Endpoints (SAVE) trial in which patients with OSA and stable CVD were randomized to receive CPAP plus usual care, or usual care alone. Serum glucose and glycated hemoglobin A(1c)(HbA(1c)) were measured at baseline, 6 months, and 2 and 4 years and incident diabetes diagnoses recorded. RESULTS Median follow-up was 4.3 years. In those with preexisting diabetes (n= 274), there was no significant difference between the CPAP and usual care groups in serum glucose, HbA(1c), or antidiabetic medications during follow-up. There were also no significant between-group differences in participants with prediabetes (n= 452) or new diagnoses of diabetes. Interaction testing suggested that women with diabetes did poorly in the usual care group, while their counterparts on CPAP therapy remained stable. CONCLUSIONS Among patients with established CVD and OSA, we found no evidence that CPAP therapy over several years affects glycemic control in those with diabetes or prediabetes or diabetes risk over standard-of-care treatment. The potential differential effect according to sex deserves further investigation.
- Sleep Apnea and Cardiovascular Disease: Lessons From Recent Trials and Need for Team Science(2017) DRAGER, Luciano F.; MCEVOY, R. Doug; BARBE, Ferran; LORENZI-FILHO, Geraldo; REDLINE, SusanEmerging research highlights the complex interrelationships between sleep-disordered breathing and cardiovascular disease, presenting clinical and research opportunities as well as challenges. Patients presenting to cardiology clinics have a high prevalence of obstructive and central sleep apnea associated with Cheyne-Stokes respiration. Multiple mechanisms have been identified by which sleep disturbances adversely affect cardiovascular structure and function. Epidemiological research indicates that obstructive sleep apnea is associated with increases in the incidence and progression of coronary heart disease, heart failure, stroke, and atrial fibrillation. Central sleep apnea associated with Cheyne-Stokes respiration predicts incident heart failure and atrial fibrillation; among patients with heart failure, it strongly predicts mortality. Thus, a strong literature provides the mechanistic and empirical bases for considering obstructive sleep apnea and central sleep apnea associated with Cheyne-Stokes respiration as potentially modifiable risk factors for cardiovascular disease. Data from small trials provide evidence that treatment of obstructive sleep apnea with continuous positive airway pressure improves not only patient-reported outcomes such as sleepiness, quality of life, and mood but also intermediate cardiovascular end points such as blood pressure, cardiac ejection fraction, vascular parameters, and arrhythmias. However, data from large-scale randomized controlled trials do not currently support a role for positive pressure therapies for reducing cardiovascular mortality. The results of 2 recent large randomized controlled trials, published in 2015 and 2016, raise questions about the effectiveness of pressure therapies in reducing clinical end points, although 1 trial supported the beneficial effect of continuous positive airway pressure on quality of life, mood, and work absenteeism. This review provides a contextual framework for interpreting the results of recent studies, key clinical messages, and suggestions for future sleep and cardiovascular research, which include further consideration of individual risk factors, use of existing and new multimodality therapies that also address adherence, and implementation of trials that are sufficiently powered to target end points and to support subgroup analyses. These goals may best be addressed through strengthening collaboration among the cardiology, sleep medicine, and clinical trial communities.
- CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea(2016) MCEVOY, R. Doug; ANTIC, Nick A.; HEELEY, Emma; LUO, Yuanming; OU, Qiong; ZHANG, Xilong; MEDIANO, Olga; CHEN, Rui; DRAGER, Luciano F.; LIU, Zhihong; CHEN, Guofang; DU, Baoliang; MCARDLE, Nigel; MUKHERJEE, Sutapa; TRIPATHI, Manjari; BILLOT, Laurent; LI, Qiang; LORENZI-FILHO, Geraldo; BARBE, Ferran; REDLINE, Susan; WANG, Jiguang; ARIMA, Hisatomi; NEAL, Bruce; WHITE, David P.; GRUNSTEIN, Ron R.; ZHONG, Nanshan; ANDERSON, Craig S.BACKGROUND Obstructive sleep apnea is associated with an increased risk of cardiovascular events; whether treatment with continuous positive airway pressure ( CPAP) prevents major cardiovascular events is uncertain. METHODS After a 1-week run-in period during which the participants used sham CPAP, we randomly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-to-severe obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care ( CPAP group) or usual care alone ( usual-care group). The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood. RESULTS Most of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness. In the CPAP group, the mean duration of adherence to CPAP therapy was 3.3 hours per night, and the mean apnea-hypopnea index ( the number of apnea or hypopnea events per hour of recording) decreased from 29.0 events per hour at baseline to 3.7 events per hour during follow-up. After a mean follow-up of 3.7 years, a primary end-point event had occurred in 229 participants in the CPAP group ( 17.0%) and in 207 participants in the usual-care group ( 15.4%) ( hazard ratio with CPAP, 1.10; 95% confidence interval, 0.91 to 1.32; P = 0.34). No significant effect on any individual or other composite cardiovascular end point was observed. CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood. CONCLUSIONS Therapy with CPAP plus usual care, as compared with usual care alone, did not prevent cardiovascular events in patients with moderate-to-severe obstructive sleep apnea and established cardiovascular disease. (Funded by the National Health and Medical Research Council of Australia and others; SAVE ClinicalTrials.gov number, NCT00738179; Australian New Zealand Clinical Trials Registry number, ACTRN12608000409370.)
- Is obstructive sleep apnoea an innocent bystander in the pathophysiology of arterial stiffening?(2018) PHILLIPS, Craig L.; DRAGER, Luciano F.
- The Effects of Long-term CPAP on Weight Change in Patients With Comorbid OSA and Cardiovascular Disease Data From the SAVE Trial(2019) OU, Qiong; CHEN, Baixin; LOFTIER, Kelly A.; LUO, Yuanming; ZHANG, Xilong; CHEN, Rui; WANG, Qian; DRAGER, Luciano F.; LORENZI, Geraldo; HLAVAC, Michael; MCARDLE, Nigel; MUKHERJEE, Sutapa; MEDIANO, Olga; BARBE, Ferran; ANDERSON, Craig S.; MCEVOY, R. Doug; WOODMAN, Richard J.BACKGROUND: Although recent evidence suggests that OSA treatment may cause weight gain, the long-term effects of CPAP on weight are not well established. METHODS: This study was a post hoc analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) study, a multicenter, randomized trial of CPAP plus standard care vs standard care alone in adults with a history of cardiac or cerebrovascular events and moderate to severe OSA. Participants with weight, BMI, and neck and waist circumferences measured at baseline and during follow-up were included. Linear mixed models were used to examine sex-specific temporal differences, and a sensitivity analysis compared high CPAP adherers ($ 4 h per night) with propensity-matched control participants. RESULTS: A total of 2,483 adults (1,248 in the CPAP group and 1,235 in the control group) were included (mean 6.1 +/- 1.5 measures of weight available). After a mean follow-up of 3.78 years, there was no difference in weight change between the CPAP and control groups, for male subjects (mean [95% CI] between-group difference, 0.07 kg [-0.40 to 0.54]; P = .773) or female subjects (mean [95% CI] between-group difference, -0.14 kg [-0.37 to 0.09]; P = .233). Similarly, there were no significant differences in BMI or other anthropometric measures. Although male participants who used CPAP >= 4 h per night gained slightly more weight than matched male control subjects without CPAP (mean difference, 0.38 kg [95% CI, 0.04 to 0.73]; P = .031), there were no between-group differences in other anthropometric variables, nor were there any differences between female high CPAP adherers and matched control subjects. CONCLUSIONS: Long-term CPAP use in patients with comorbid OSA and cardiovascular disease does not result in clinically significant weight change.