Positive airway pressure therapy for post-stroke sleep disordered breathing: a systematic review, meta-analysis and meta-regression

Zheng An Toh; Ling Jie Cheng; Xi Vivien Wu; Deidre Anne De Silva; Hui Xian Oh; Si Xian Ng; Hong-Gu He; Minna Pikkarainen

doi:10.1183/16000617.0169-2022

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FIGURE 1
PRISMA-P flowchart for selection of studies included in the meta-analysis. PAP: positive airway pressure therapy; SDB: sleep disordered breathing.
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FIGURE 2
Forest plot of risk ratio or Hedges’ g (95% CI) showing the effectiveness of positive airway pressure therapy (PAP) on a) recurrent vascular events, b) neurological deficit, c) cognition, d) functional independence, e) daytime sleepiness and f) depression. SMD: standardised mean difference.

TABLE 1

Characteristics of the included studies (n=24)

First author [ref.]	Year	Country	Total and group sample size (n); age (years)^#	Stroke phase	Stroke type; SDB type	Attrition rate (n/N (%))	Missing data management	Funding; protocol registration
Aaronson [25]	2016	The Netherlands	T: 36 I: 20; 61.1±8.2 C: 16; 56.7±8.8	16.8 days after stroke	Ischaemic and haemorrhagic; OSA	I: 3/20 (15) C: 2/16 (12.5) T: 5/36 (13.9)	ITT analysis	No; yes
Bernasconi [88]	2020	Switzerland, Germany, Italy	T: 41 I: 19; 64.1±6.7 C: 22; 64.7±6.6	3 months after stroke	Ischaemic; CSA and OSA	I: 3/19 (15.8) C: 4/22 (18.2) T: 7/41 (17.1)	ITT analysis	Yes; yes
Bravata [23]	2011	USA	T: 55 I: 31; 70.6±9.4 C: 24; 71.6±13.3	≤72 h of stroke	Ischaemic; CSA and OSA	I: 9/31 (29) C: 3/24 (12.5) T: 12/55 (21.8)	ITT analysis	Yes; yes
Bravata [54]	2010	USA	T: 70 I: 31; 66.3±11.9 C: 24; 67.4±12.8	Majority ≤48 h of stroke	TIA; CSA and OSA	I: 9/45 (20) C: 5/25 (20) T: 14/70 (20)	ITT analysis	Yes; yes
Brown [55]	2013	USA	T: 32 I: 15; 61±22.22 C: 17; 70±19.3	≤7 days of stroke	Ischaemic; CSA and OSA	I: 7/15 (46.7) C: 6/17 (35.3) T: 13/32 (40.6)	Unreported	Yes; yes
Cui [52]	2017	China	T: 145 I: 73; 66.2±5.6 C: 72; 68.4±13.9	Unspecified	Ischaemic; OSA	Unreported	Unreported	Unreported; no
Dong [61]	2017	China	T: 80; 38–74	Unspecified; acute phase	Ischaemic; OSA	Unreported	Per-protocol analysis	Yes; no
Gao [62]	2013	China	T: 78 I: 44; 67.93±7.28 C: 34; 67.68±6.54	Unspecified; acute phase	Ischaemic; OSA	Unreported	Unreported	Unreported; no
Gupta [89]	2018	India	T: 70 I: 30; 24±80 C: 40; 33±82.5	≥6 weeks after stroke	Ischaemic and haemorrhagic; OSA	I: 4/34 (11.8) C: 0	Crossed over from I to C	Yes; yes
Hsu [26]	2006	UK	T: 30 I: 15; 76±5.93 C: 15; 71.67±8.89	Days 21–25 after stroke	No restriction; unclear	I: 5/15 33.3 C: 0 T: 5/30 (16.7)	ITT analysis	Yes; no
Kim [73]	2019	South Korea	T: 43 I: 20; 63.3±13.1 C: 20; 66.9±12.3	4.6±2.8 days after stroke onset	Ischaemic and haemorrhagic; CSA, OSA and mixed apnoea	I: 3/23 (13) C: 0 T: 3/43 (7)	Withdrawn patients excluded	Yes; yes
Li [63]	2020	China	T: 82 I: 39; 59.95±4.17 C: 43; 60.21±5.97	Unspecified	Ischaemic; OSA	Unreported	Per-protocol analysis	Unreported; no
Liu [58]	2014	China	T: 71 I: 34; 62.05±8.30 C: 37; 61.89±8.09	Unspecified	Ischaemic; OSA	Unreported	Unreported	Unreported; no
Ning [66]	2019	China	T: 80 I: 37; 69.37±5.67 C: 43; 68.37±5.15	Unspecified; non-acute stroke	Ischaemic; OSA	Unreported	Unreported	Unreported; no
Parra [22]	2015	Spain	T: 140 I: 57; 63.7±9.1 C: 69; 65.5±9.1	4.6±2.8 days after stroke onset	Ischaemic; CSA and OSA	I: 14/71 (19.7) C: 0 T: 14/140 (10)	Per-protocol analysis	Yes; yes
Parra [60]	2011	Spain	T: 140 I: 57; 63.7±9.1 C: 69; 65.5±9.1	4.6±2.8 days after stroke onset	Ischaemic; CSA and OSA	I: 14/71 (19.7) C: 0 T: 14/140 (10)	Per-protocol analysis	Yes; yes
Ryan [24]	2011	Canada	T: 48 I: 22; 62.8±12.8 C: 22; 60.7±10.3	Within 3 weeks of stroke onset	Ischaemic and haemorrhagic; OSA	I: 3/25 (12) C: 1/23 (4.3) T: 4/48 (8.3)	Withdrawn patients excluded	Yes; yes
Sandberg [90]	2001	Sweden	T: 63 I: 31; 78.1±6.4 C: 28; 76.8±7.9	2–4 weeks after stroke	Ischaemic and haemorrhagic; CSA and OSA	I: 2/33 (6.1) C: 2/30 (6.7) T: 4/63 (6.3)	Missing data were replaced with mean	Yes; no
Su [68]	2011	China	T: 60 I: 30; 56–76 C: 30; 58–73	Unspecified; acute phase	Ischaemic; OSA	Unreported	Unreported	Unreported; no
Tu [64]	2015	China	T: 140 I: 70; 48.15±9.85 C: 70; 47.68±8.96	Within 1 week of stroke	Ischaemic; OSA	Unreported	Unreported	Unreported; no
Wan [67]	2018	China	T: 49 I: 20; 63.32±11.79 C: 29; 57.48±10.40	Unspecified; during hospitalisation	Unspecified; OSA	I: 5/25 (20) C: 0/29 T: 5/54 (9.3)	Withdrawn patients excluded	Yes; no
Wang [91]	2015	China	T: 86 I: 43; 64.5±9.7 C: 43; 64.2±8.6	Unspecified; acute phase	Ischaemic; OSA	Unreported	Unreported	Unreported; no
Xu [65]	2020	China	T: 81 I: 41; 68.2±11.8 C: 40; 69.1±12.3	Unspecified; non-acute stroke	Ischaemic; OSA	Unreported	Unreported	Unreported; no
Yuan [59]	2016	China	T: 107 I: 51; 65.2±14.6 C: 56; 64.4±13.9	Unspecified	Unspecified; OSA	Unreported	Unreported	Unreported; no

^#: Age data are presented as mean±sd or range. SDB: sleep disordered breathing; T: total; I: intervention; C: control; OSA: obstructive sleep apnoea; ITT: intention-to-treat; CSA: central sleep apnoea; TIA: transient ischaemic attack.

TABLE 2

Subgroup analyses of primary and secondary outcomes (n=24 studies)

Outcome and subgroups	Studies (n)	Total (n)	Risk ratio^# or Hedges’ g^¶	95% CI	95% PI	Heterogeneity I² (%), τ², p-value	z-test, p-value⁺	Subgroup difference (χ²), p-value⁺
Recurrent vascular events (n=8)
Follow-up period
≤12 months	6	518	0.45	0.23–0.87	0.08–2.57	7, 0.28, 0.37	−2.37, 0.02	0.01, 0.92
>12 months	2	160	0.42	0.18–0.97		0, <0.01, 0.94	−2.03, 0.04
Adherence
<4 h								NA
≥4 h	8	678	0.47	0.28–0.78	0.14–1.58	0, 0.18, 0.55	−2.91, <0.01
Stroke phase
<2 weeks	3	251	0.36	0.16–0.80	0.00–97.19	0, 0.03, 0.75	−2.51, 0.01	0.42, 0.81
≥2 weeks	2	104	0.26	0.05–1.46		0, 0.005, 0.79	−1.53, 0.13
PAP device
Auto-CPAP	7	552	0.46	0.25–0.85	0.11–1.96	0, 0.22, 0.49	−2.51, 0.01	0.02, 0.88
CPAP
Nasal CPAP	1	126	0.43	0.18–1.01
Baseline SDB severity
AHI ≤30 events·h⁻¹	5	448	0.46	0.22–0.98	0.05–4.37	11, 0.35, 0.35	−2.02, 0.04	0.10, 0.75
AHI >30 events·h⁻¹	3	230	0.39	0.17–0.85	0.00–77.20	0, 0.01, 0.85	−2.37, 0.02
Neurological deficit (n=12)
Follow-up period
≤3 months	11	756	−0.73	−1.05– −0.41	−1.85–0.39	78, 0.22, <0.01	−4.43, <0.01	1.19, 0.55
3–6 months	2	162	−1.32	−3.28–0.64		97, 1.92, <0.01	−1.32, 0.19
>6 months	2	233	−0.30	−1.20–0.61		92, 0.39, <0.01	−0.64, 0.52
Adherence
<4 h	3	85	−0.29	−0.73–0.15	−3.36–2.78	0, 0.01, 0.76	−1.28, 0.20	8.45, 0.01
≥4 h	8	638	−0.92	−1.45– −0.38	−2.81–0.98	90, 0.53, <0.01	−3.37, <0.01
Stroke phase
<2 weeks	4	325	−0.34	−0.93–0.25	−2.96–2.28	89, 0.28, <0.01	−1.13, 0.26	4.72, 0.09
≥2 weeks	4	191	−0.68	−1.05– −0.31	−1.93–0.56	17, 0.05, 0.31	−3.63, <0.01
PAP device
Auto-CPAP	5	425	−0.97	−1.45– −0.49	−2.66–0.73	65, 0.22, 0.02	−3.98, <0.01	10.83, 0.01
CPAP	4	242	−1.08	−1.92– −0.25	−4.97–2.80	88, 0.63, <0.01	−2.55, 0.01
Nasal CPAP	2	156	0.02	−0.45–0.49		31, 0.05, 0.23	0.09, 0.93
Baseline SDB severity
AHI ≤30 events·h⁻¹	6	470	−1.13	−1.75– −0.50	−3.32–1.07	84, 0.52, <0.01	−3.54, <0.01	8.22, 0.02
AHI >30 events·h⁻¹	5	312	−0.31	−0.67–0.05	−1.42–0.80	66, 0.09, 0.02	−1.69, 0.09
Cognition (n=8)
Follow-up period
≤1 month	4	225	0.28	−0.16–0.73	−1.55–2.12	60, 0.13, 0.06	1.24, 0.22	2.79, 0.25
1–3 months	3	161	0.25	−0.12–0.62	−2.92–3.42	0, 0.03, 0.42	1.33, 0.18
3–6 months	3	232	1.77	0.02–3.53	−20.7–24.2	96, 2.32, <0.01	1.98, 0.05
Adherence
<4 h	1	30	−0.10	−0.81–0.62				3.43, 0.06
≥4 h	7	424	0.98	0.10–1.86	−2.20–4.16	92, 1.33, <0.01	2.17, 0.03
Stroke phase
<2 weeks	1	40	0.64	0.00–1.28				0.32, 0.85
≥2 weeks	5	283	1.01	−0.30–2.32	−4.12–6.14	95, 2.15, <0.01	1.51, 0.13
PAP device
Auto-CPAP	2	119	0.54	−0.07–1.16		65, 0.13, 0.09	1.73, 0.08	7.18, 0.07
CPAP	3	206	1.75	−0.03–3.54	−21.0–24.5	95, 2.39, <0.01	1.93, 0.05
Nasal CPAP	2	89	−0.06	−0.48–0.35		0, <0.01, 0.92	−0.30, 0.76
Baseline SDB severity
AHI ≤30 events·h⁻¹	2	126	0.87	0.50–1.23		0, <0.01, 0.70	4.60, <0.01	62.0, <0.01
AHI >30 events·h⁻¹	5	248	0.33	−0.06–0.72	−0.91–1.56	55, 0.11, 0.07	1.64, 0.10
Functional independence (n=17)
Follow-up period
≤3 months	13	765	0.29	−0.10–0.68	−1.21–1.79	85, 0.42, <0.01	1.46, 0.14	0.93, 0.63
3–6 months	5	342	0.93	−0.32–2.19	−3.96–5.83	95, 1.95, <0.01	1.46, 0.14
>6 months	4	336	0.34	−0.13–0.81	−1.70–2.38	80, 0.17, <0.01	1.42, 0.16
Adherence
<4 h	3	85	−0.14	−0.64–0.36	−4.39–4.11	0, 0.05, 0.44	−0.56, 0.58	4.38, 0.11
≥4 h	12	880	0.63	0.11–1.16	−1.45–2.72	89, 0.81, <0.01	2.35, 0.02
Stroke phase
<2 weeks	3	185	−0.03	−0.44–0.38	−3.91–3.85	0, 0.05, <0.01	1.35, 0.18	3.68, 0.16
≥2 weeks	8	433	0.56	−0.25–1.37	−2.39–3.51	92, 1.28, 0.00	1.52, 0.13
PAP device
Auto-CPAP	6	388	0.42	−0.05–0.89	−1.14–1.98	75, 0.26, <0.01	1.77, 0.08	3.85, 0.28
CPAP	6	382	0.71	−0.42–1.84	−3.44–4.87	95, 1.91, <0.01	1.24, 0.22
Nasal CPAP	3	215	0.02	−0.26–0.30	−1.90–1.94	0, <0.01, 0.78	0.15, 0.88
Baseline SDB severity
AHI ≤30 events·h⁻¹	5	330	0.48	−0.12–1.08	−1.72–2.68	79, 0.38, <0.01	1.57, 0.12	2.83, 0.24
AHI >30 events·h⁻¹	8	474	0.11	−0.09–0.31	−0.26–0.47	0, 0.01, 0.83	1.05, 0.30
Daytime sleepiness (n=11)
Follow-up period	9	440	−0.59	−1.06– −0.13	−2.20–1.01	80, 0.40, <0.01	−2.50, 0.01	1.96, 0.38
≤3 months	3	221	−1.57	−3.26–0.12	−23.2–20.1	96, 2.15, <0.01	−1.82, 0.07
3–6 months	3	248	−0.91	−1.24– −0.58	−3.98–2.15	18, 0.03, 0.29	−5.42, <0.01
Adherence
<4 h	3	85	0.14	−0.30–0.58	−2.91–3.19	0, 0.01, 0.72	0.61, 0.54	21.4, <0.01
≥4 h	7	471	−1.37	−2.05– −0.70	−3.76–1.01	88, 0.74, <0.01	4.45, 0.00
Stroke phase
<2 weeks	2	59	−0.46	−1.56–0.64		76, 0.46, 0.04	−0.82, 0.41	0.86, 0.65
≥2 weeks	6	341	−1.17	−2.21– −0.14	−4.95–2.60	93, 1.57, <0.01	−2.22, 0.03
PAP device
Auto-CPAP	6	397	−0.88	−1.32– −0.43	−2.34–0.59	66, 0.23, 0.01	−3.86, <0.01	10.45, 0.02
CPAP	3	160	−1.64	−3.48–0.19	−25.0–21.8	96, 2.51, <0.01	−1.75, 0.08
Nasal CPAP	1	30	0.35	−0.38–1.07
Baseline SDB severity
AHI ≤30 events·h⁻¹	4	241	−0.87	−1.56– −0.17	−4.00–2.26	73, 0.40, 0.01	−2.44, 0.01	4.79, 0.09
AHI >30 events·h⁻¹	5	225	−0.49	−1.00–0.02	−2.25–1.27	67, 0.24, 0.02	−1.88, 0.06
Depression (n=7)
Follow-up period
≤1 month	3	139	−0.33	−0.79–0.14	−5.00–4.34	40, 0.08, 0.19	−1.38, 0.17	0.08, 0.78
>1 month	4	178	−0.75	−3.70–2.2	−15.1–13.6	97, 8.86, <0.01	−0.50, 0.62
Adherence
<4 h	3	85	0.94	−0.30–2.18	−14.1–15.9	80, 0.99, <0.01	1.49, 0.14	4.95, 0.03
≥4 h	4	232	−1.71	−3.69–0.27	−11.3–7.89	96, 3.96, <0.01	−1.69, 0.09
Stroke phase
<2 weeks	1	19	2.30	1.08–3.53				25.2, <0.01
≥2 weeks	5	249	−0.98	−2.85–0.90	−8.35–6.39	96, 4.45, <0.01	−1.02, 0.31
PAP device
Auto-CPAP	2	68	0.51	−2.86–3.88		96, 5.67, <0.01	0.30, 0.77	1.11, 0.57
CPAP	3	160	−1.64	−4.65–1.38	−40.5–37.2	98, 6.98, <0.01	−1.06, 0.29
Nasal CPAP	2	89	−0.03	−1.33–1.27		89, 0.78, <0.01	−0.04, 0.97
Baseline SDB severity
AHI ≤30 events·h⁻¹	2	63	0.95	−1.53–3.42		93, 2.95, <0.01	0.75, 0.45	60.5, <0.01
AHI >30 events·h⁻¹	4	174	−0.30	−1.10–0.51	−3.98–3.39	83, 0.57, <0.01	−0.72, 0.47

95% CI: 95% confidence interval; 95% PI: 95% prediction interval; (C)PAP: (continuous) positive airway pressure; SDB: sleep disordered breathing; AHI: apnoea–hypopnoea index; NA: not applicable. ^#: risk ratio was used to report recurrent vascular events only; ^¶: Hedges' g was used to report neurological deficit, cognition, functional independence and daytime sleepiness; ⁺: bold indicates statistically significant.

TABLE 3

Results of random effects univariate meta-regression on neurological deficit, functional independence and daytime sleepiness

	Neurological deficit				Functional independence				Daytime sleepiness
	β	se	95% CI	p-value	β	se	95% CI	p-value	β	se	95% CI	p-value
Mean age	0.03	0.03	−0.04–0.09	0.44	−0.01	0.02	−0.03–0.06	0.61	−0.003	0.03	−0.06–0.05	0.92
Proportion of males	0.03	0.02	−0.12–0.07	0.23	0.001	0.01	−0.03–0.03	0.93	−0.06	0.02	−0.10– −0.01	0.01*
Sample size	−0.004	0.01	−0.02–0.01	0.48	0.01	0.01	−0.004–0.03	0.16	−0.02	0.01	−0.04–0.002	0.08
Year of publication	−0.08	0.04	−0.17–0.02	0.11	0.08	0.04	0.004–0.16	0.04*	−0.12	0.07	−0.26–0.02	0.08

*: p<0.05.

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