Who May Benefit From Diuretics in OSA?: A Propensity Score-Match Observational Study

doi:10.1016/j.chest.2020.01.050

Chest

Volume 158, Issue 1, July 2020, Pages 359-364

https://doi.org/10.1016/j.chest.2020.01.050 Get rights and content

Background

Diuretics have been reported as effective for reducing OSA severity by preventing fluid retention and reducing rostral fluid shift. The benefit of diuretics might vary depending on the OSA clinical phenotype and comorbidities. To test this hypothesis, we conducted a propensity score-matched cohort analysis of data from the French national sleep apnea registry “Observatoire Sommeil de la Fédération de Pneumologie.”

Research Question

Which phenotypic subtypes of OSA may benefit from diuretics?

Study Design and Methods

A propensity score analysis was used to determine the impact of diuretics on OSA severity. Matching (ratio 1:4) was performed by using a 0.1 collider for the propensity score. Severe OSA was defined as an apnea-hypopnea index (AHI) > 30 events/h, and the usefulness of diuretics was assessed by using a logistic regression model.

Results

The 69,564 OSA patients studied in the OSFP prospective observational cohort had a median age of 56.9 years (interquartile range: 47.4; 65.6), 67% were men, and the median AHI was 28 (14; 43) events/h. Among them, 9,783 (14.1%) were treated with diuretics. Diuretics reduced OSA severity in overweight or moderately obese patients (P = .03) and in patients with hypertension (P < .01), particularly in patients with hypertension with a BMI between 25 and 35 (P < .01). Diuretics had no significant effect on OSA severity in patients with self-reported low physical activity or heart failure.

Interpretation

Diuretics appear to have a positive impact on OSA severity in overweight or moderately obese patients with hypertension. A prospective study is needed to confirm that diuretics are of interest in combined therapies for hypertensive patients with OSA.

Section snippets

Study Design and Setting: The OSFP National Registry

Data from the prospective national OSFP cohort were used to conduct this study. The OSFP registry¹³ is a standardized web-based reporting system administered by the French Federation of Pulmonology. It contains anonymized longitudinal data from patients complaining of sleep disorders whose conditions have been investigated by respiratory physicians in private practice, general hospitals, and university hospitals. Periodic quality control checks are performed to ensure up-to-standard data

Results

As shown in the study flowchart (Fig 1), the overall population extracted in June 2019 included 101,791 patients. Among them, 69,564 exhibited OSA, with an AHI or oxygen desaturation index > 5 events/h. The number of patients on diuretic treatment at the time of OSA diagnosis was 9,783 (14.1%).

Discussion

Our results, obtained from a propensity score-matched analysis in a very large prospective observational cohort (N = 69,564) with real-life recruitment of OSA patients, confirm, expand, and clarify previous data. In a series of 15 obese patients with hypertension and diastolic heart failure, intensive treatment with diuretics (IV administration of furosemide + spironolactone for 3 days) significantly decreased body weight, BP, and AHI.⁸ Our results showed that the beneficial effect of diuretics

Conclusions

These findings provide further evidence that fluid redistribution from the legs to the neck during sleep contributes to the severity of OSA in patients with hypertension and may be a significant link between these two conditions. Thus, an association between diuretic use and decreased severity of OSA in overweight or moderately obese or hypertensive patients has been shown. A prospective study is needed to clarify these findings and identify which class of diuretics is of interest in this

Acknowledgments

Author contributions: B. R., I. J.-D., and S. B. contributed to the study design, analysis and interpretation of the data, and drafting and revising the manuscript. R. T., Y. G., and M. S. were responsible for acquisition of data, contributed to the discussion, and reviewed the manuscript. M. J.-F. and J.-L. P. were responsible for study concept and design, supervised the study, and critically revised the manuscript. J.-L. P. is the guarantor of this work and, as such, had full access to all of

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Citation Excerpt :
Severity of OSA was not significantly reduced by any of the medications (p = 0.059 for main effect of the treatment factor) [30]. Recently, a prospective observational cohort study used propensity-score matched analysis of 69,564 individuals with OSA, of which 9783 were treated with diuretics, and found OSA severity decreased in participants with a BMI between 25 kg/m2 and 35 kg/m2 (p < 0.01), and in participants with a history of hypertension (p < 0.01) [31]. Pro-inflammatory cytokines including interleukins (IL)-1, IL-6, IL-8 (CXCL8), and tissue necrosis factor-alpha (TNF-alpha), along with intercellular adhesion molecules that promote immune cell trafficking and inflammation in local tissues, are elevated in the serum of individuals with OSA [32–37], and implicated in the development of many consequences of associated with OSA, including cardiovascular disease, obesity, metabolic syndrome, excessive daytime sleepiness, and fatigue [33–35,38–41].
Obstructive sleep apnea (OSA) is the most common form of sleep-disordered breathing characterized by intermittent partial or complete closure of the upper airway during sleep. If left untreated, OSA is associated with adverse cardiovascular outcomes such as hypertension, coronary heart disease, heart failure, cardiac arrhythmia, stroke, and death. Positive airway pressure (PAP) is often considered the first-line treatment for OSA. While PAP can be very effective in reducing the number of obstructive apneas and hypopneas, its impact on prevention of adverse cardiovascular consequences remains controversial, and treatment adherence is often poor. Hence, the necessity for novel treatment options to help those who cannot adhere to positive airway pressure treatment. Different classes of medications have been tested with regards to their effect on OSA severity. This review 1) provides an update on the epidemiology and pathophysiology of OSA, 2) outlines the mechanistic rationale for medication classes tested as OSA treatment and 3) discusses the effects of these medications on OSA. Several wake-promoting medications are approved for management of persistent sleepiness despite OSA treatment; discussion of these symptomatic treatments is outside the scope of this review. Herein, the authors review the current evidence for pharmacological management of OSA and provide future directions.
Blood pressure control in hypertensive sleep apnoea patients of the European Sleep Apnea Database cohort - effects of positive airway pressure and antihypertensive medication
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Association between Obstructive Sleep Apnea and Heart Failure in Adults—A Systematic Review
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2023, Journal of Sleep Research
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: Drs Revol and Jullian-Desayes contributed equally to this work.

: Drs Joyeux-Faure and Pépin contributed equally to this work.

: FUNDING/SUPPORT: B. R., I. J. D., M. J. F., S. B., R. T., and J. L. P. are supported by a research grant from the French National Research Agency (ANR-12-TECS-0010), in the framework of the “Investissements d’avenir” program (ANR-15-IDEX-02) and by the “e-health and integrated care and trajectories medicine MIAI artificial intelligence” Chairs of excellence from the Grenoble Alpes University Foundation.

^∗: Collaborators from the OSFP National French Registry Scientific Council are listed in the Acknowledgments.

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Sleep: Original ResearchWho May Benefit From Diuretics in OSA?: A Propensity Score-Match Observational Study

Background

Research Question

Study Design and Methods

Results

Interpretation

Section snippets

Study Design and Setting: The OSFP National Registry

Results

Discussion

Conclusions

Acknowledgments

Lancet Respir Med

Sleep Med Rev

Chest

Lancet Respir Med

Pharmacol Ther

Obstructive sleep apnoea syndrome

Nat Rev Dis Primer

Impact of concomitant medications on obstructive sleep apnoea

Br J Clin Pharmacol

Pharmacotherapy of obstructive sleep apnea

Expert Opin Pharmacother

Non-CPAP therapies in obstructive sleep apnoea

Eur Respir J

Drug therapy for obstructive sleep apnoea in adults

Cochrane Database Syst Rev

Sleep: Original Research
Who May Benefit From Diuretics in OSA?: A Propensity Score-Match Observational Study