Abstract
Background
Ischaemic heart disease including heart failure is the most common cause of death in the world, and the incidence of the condition is rapidly increasing. Heart failure is characterised by symptoms such as fatigue and breathlessness during light activity, as well as disordered breathing during sleep. In particular, sleep disordered breathing (SDB), including central sleep apnoea (CSA) and obstructive sleep apnoea (OSA), is highly prevalent in people with chronic heart failure. A previous meta‐analysis demonstrated that positive airway pressure (PAP) therapy dramatically increased the survival rate of people with heart failure who had CSA, and thus could contribute to improving the prognosis of these individuals. However, recent trials found that adaptive servo‐ventilation (ASV) including PAP therapy had a higher risk of all‐cause mortality and cardiovascular mortality. A meta‐analysis that included recent trials was therefore needed.
Objectives
To assess the effects of positive airway pressure therapy for people with heart failure who experience central sleep apnoea.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, and Web of Science Core Collection on 7 February 2019 with no limitations on date, language, or publication status. We also searched two clinical trials registers in July 2019 and checked the reference lists of primary studies.
Selection criteria
We excluded cross‐over trials and included individually randomised controlled trials, reported as full‐texts, those published as abstract only, and unpublished data.
Data collection and analysis
Two review authors independently extracted outcome data from the included studies. We double‐checked that data had been entered correctly by comparing the data presented in the systematic review with study reports. We analysed dichotomous data as risk ratios (RRs) with 95% confidence intervals (CIs) and continuous data as mean difference (MD) or standardised mean difference (SMD) with 95% CIs. Furthermore, we performed subgroup analysis in the ASV group or continuous PAP group separately. We used GRADEpro GDT software to assess the quality of evidence as it relates to those studies that contribute data to the meta‐analyses for the prespecified outcomes.
Main results
We included 16 randomised controlled trials involving a total of 2125 participants. The trials evaluated PAP therapy consisting of ASV or continuous PAP therapy for 1 to 31 months. Many trials included participants with heart failure with reduced ejection fraction. Only one trial included participants with heart failure with preserved ejection fraction.
We are uncertain about the effects of PAP therapy on all‐cause mortality (RR 0.81, 95% CI 0.54 to 1.21; participants = 1804; studies = 6; I2 = 47%; very low‐quality evidence). We found moderate‐quality evidence of no difference between PAP therapy and usual care on cardiac‐related mortality (RR 0.97, 95% CI 0.77 to 1.24; participants = 1775; studies = 5; I2 = 11%). We found low‐quality evidence of no difference between PAP therapy and usual care on all‐cause rehospitalisation (RR 0.95, 95% CI 0.70 to 1.30; participants = 1533; studies = 5; I2 = 40%) and cardiac‐related rehospitalisation (RR 0.97, 95% CI 0.70 to 1.35; participants = 1533; studies = 5; I2 = 40%). In contrast, PAP therapy showed some indication of an improvement in quality of life scores assessed by all measurements (SMD −0.32, 95% CI −0.67 to 0.04; participants = 1617; studies = 6; I2 = 76%; low‐quality evidence) and by the Minnesota Living with Heart Failure Questionnaire (MD −0.51, 95% CI −0.78 to −0.24; participants = 1458; studies = 4; I2 = 0%; low‐quality evidence) compared with usual care. Death due to pneumonia (N = 1, 3% of PAP group); cardiac arrest (N = 18, 3% of PAP group); heart transplantation (N = 8, 1% of PAP group); cardiac worsening (N = 3, 9% of PAP group); deep vein thrombosis/pulmonary embolism (N = 1, 3% of PAP group); and foot ulcer (N = 1, 3% of PAP group) occurred in the PAP therapy group, whereas cardiac arrest (N = 16, 2% of usual care group); heart transplantation (N = 12, 2% of usual care group); cardiac worsening (N = 5, 14% of usual care group); and duodenal ulcer (N = 1, 3% of usual care group) occurred in the usual care group across three trials.
Authors’ conclusions
The effect of PAP therapy on all‐cause mortality was uncertain. In addition, although we found evidence that PAP therapy did not reduce the risk of cardiac‐related mortality and rehospitalisation, there was some indication of an improvement in quality of life for heart failure patients with CSA. Furthermore, the evidence was insufficient to determine whether adverse events were more common with PAP than with usual care. These findings were limited by low‐ or very low‐quality evidence. PAP therapy may be worth considering for individuals with heart failure to improve quality of life.
Plain language summary
Positive airway pressure for heart failure associated with central sleep apnoea
Background
Ischaemic heart disease including heart failure is the most common cause of death in the world, and the incidence of the condition is rapidly increasing. Heart failure is characterised by symptoms such as fatigue and breathlessness during light activity, as well as disordered breathing during sleep. In particular, sleep disordered breathing, including central sleep apnoea (CSA) and obstructive sleep apnoea, is highly prevalent in people with chronic heart failure.
Purpose: to assess the effects of positive airway pressure (PAP) therapy for people with heart failure who experience CSA.
Methods
We searched the scientific literature for randomised controlled trials (RCTs) (a type of study in which participants are assigned to one of two or more treatment groups by means of a random method) that compared the effectiveness of PAP therapy versus usual care in people with heart failure who experience CSA. PAP therapy consisted of continuous PAP and adaptive servo‐ventilation, and usual care consisted of medical therapy based on relevant guidelines. The evidence is current to February 2019.
Results
We included 16 RCTs involving a total of 2125 participants. The effect of PAP therapy on on all‐cause mortality was uncertain. In addition, PAP therapy did not reduce cardiac‐related mortality, all‐cause rehospitalisation, and cardiac‐related rehospitalisation compared with usual care. However, PAP therapy showed some indication of an improvement in quality of life scores. Death due to pneumonia (N = 1, 3% of PAP group); cardiac arrest (N = 18, 3% of PAP group); heart transplantation (N = 8, 1% of PAP group); cardiac worsening (N = 3, 9% of PAP group); deep vein thrombosis/pulmonary embolism (N = 1, 3% of PAP group); and foot ulcer (N = 1, 3% of PAP group) were observed in the PAP therapy group, whereas cardiac arrest (N = 16, 2% of usual care group); heart transplantation (N = 12, 2% of usual care group); cardiac worsening (N = 5, 14% of usual care group); and duodenal ulcer (N = 1, 3% of usual care group) occurred in the usual care group across three trials.
Quality of the evidence
We assessed the the quality of evidence for many outcomes including cardiac‐related rehospitalisation as low or very low because variability among studies (heterogeneity) was high, a range of confidence intervals was wide, and random sequence generation and blinding of participants and personnel were poorly described.
Conclusion
The effect of PAP therapy on all‐cause mortality was uncertain. In addition, although PAP therapy did not reduce the risk of cardiac‐related mortality and rehospitalisation, there was some indication of an improvement in quality of life score for heart failure patients with CSA. Furthermore, the evidence was insufficient to determine whether adverse events were more common with PAP than with usual care. These findings were limited by low‐ or very low‐quality evidence. PAP therapy may be worth considering for individuals with heart failure to improve quality of life.
