Does continuous positive airway pressure therapy benefit patients with coronary artery disease and obstructive sleep apnea? A systematic review and meta‐analysis

Abstract The prevalent co‐morbidity of coronary artery disease (CAD) and obstructive sleep apnea (OSA) has attracted great interest. However, effects of continuous positive airway pressure (CPAP) in patients with OSA and CAD for cardiovascular outcomes and deaths are still controversial. Usage of CPAP among patients with CAD and OSA could decrease the risk of cardiovascular events and death in adults. PubMed, EMBASE, Web of science, and Cochrane Library were systematically searched. Studies that described association of CPAP treatment with cardiovascular events in CAD and OSA patients were included. The main outcome was the major adverse cardiovascular events (MACE), including all‐cause death, cardiovascular death, myocardial infarction (MI), stroke, and repeat revascularization. Summary relative risks (risk ratios [RRs]) and 95% confidence intervals (CIs) of outcomes were pooled and heterogeneity was assessed with the I2 statistic. Nine studies enrolling 2590 participants with OSA and CAD were included and extracted data. There was significant association of CPAP with reduced risk of MACE (RR, 0.73, 95% CI [0.55, 0.96]), particularly among those with AHI less than 30 events/h (RR, 0.43, 95% CI [0.22, 0.84]). Similarly, the same result was found in all‐cause death (RR, 0.66, 95% CI, [0.46, 0.94]) and cardiovascular death (RR, 0.495, 95% CI [0.292, 0.838]). Our data suggested that CPAP usage, compared to usual care, was associated with reduced risks of cardiovascular outcomes or death in patients with OSA and CAD, particularly in the subgroup with AHI less than 30 events/h, which still needs further studies to confirm.


Rationale
3 Describe the rationale for the review in the context of what is already known.

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Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

METHODS
Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.

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Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.

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Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

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Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.

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Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).

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Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

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Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

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Risk of bias in individual studies 12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.

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Summary measures 13 State the principal summary measures (e.g., risk ratio, difference in means).

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Synthesis of results 14 Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I 2 ) for each meta-analysis.
8 Section/topic # Checklist item Reported on page # Risk of bias across studies 15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).

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Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

RESULTS
Study selection 17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.

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Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

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Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).

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Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.

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Synthesis of results 21 Present results of each meta-analysis done, including confidence intervals and measures of consistency.

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Risk of bias across studies 22 Present results of any assessment of risk of bias across studies (see Item 15).

DISCUSSION
Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).

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Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

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Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research.