Influence of enhanced external counterpulsation on endothelial function: a meta-analysis of randomized controlled trials

Figures & data

Figure 1. Flowchart of literature search.

Table 1. Characteristics of the included RCTs.

Study	Country	Design	Patient diagnosis	No of patients	Mean age (years)	Men (%)	Smoking (%)	Mean FMD at baseline (%)	EECP protocol	Control	Treatment duration (weeks)	Accumulating duration of EECP (h)	FMD measurement
Wang 2006	China	R, OL	MetS	50	53.8	46	28	5.94	60 min, 6 days/week	Usual care	6	36	Forearm inflating to 240 mmHg for 5 min
Braith 2010	USA	R, DB, PC	Stable CAD	42	64.3	81	0	4.02	60 min, daily	Sham EECP	7	42	Forearm inflating to 200 mmHg for 5 min
Gloekler 2010	Switzerland	R, DB, PC	Stable CAD	20	63	85	15	5.15	90 min, 5 days/week	Sham EECP	4	30	Forearm inflating to 200 mmHg for 5 min
Chen 2011	China	R, OL	CAD after PCI	165	58	59.4	NR	4.41	60 min, 5 days/week	Conventional therapy	4	20	Forearm inflating to 200 mmHg for 5 min
Martin 2012	USA	R, OL	IGT	18	64.2	NR	NR	3.02	60 min, daily	Usual care	7	49	Forearm inflating to 200 mmHg for 5 min
Xiao 2015	China	R, OL	Ischemic stroke	80	40.5	53.8	NR	4.62	60 min, daily	Conventional therapy	4	28	Forearm inflating to 200 mmHg for 5 min
Chen 2015	China	R, OL	CAD after PCI	30	58.5	66.7	53.3	6.08	60 min, daily	Conventional therapy	5	35	Forearm inflating to 240 mmHg for 5 min
Zheng 2016	China	R, OL	CAD and hypertension	120	68.4	47.5	62.5	6.93	60 min, twice daily	Conventional therapy	3	42	Forearm inflating to 200 mmHg for 5 min
Jiang 2019	China	R, OL	Stable CAD	156	59.3	53.2	NR	3.34	60 min, 6 days/week	Conventional therapy	6	36	Forearm inflating to 200 mmHg for 5 min
Liu 2019	China	R, OL	UA	100	62.1	59	52	6.44	30 min, twice daily	Conventional therapy	4	28	Forearm inflating to 200 mmHg for 5 min
Zhang 2019	China	R, OL	CSFP	50	62.1	52	40	4.25	45 min, twice daily	Usual care	4	42	Forearm inflating to 200 mmHg for 5 min
Tan 2019	China	R, OL	Stable CAD after PCI	89	56.7	52.8	25.8	7.45	90 min, 5 days/week	Conventional therapy	7	52.5	Forearm inflating to 240 mmHg for 5 min
Qiao 2020	China	R, OL	Stable CAD	68	61.3	57.4	NR	4.11	60 min, daily	Conventional therapy	7	49	Forearm inflating to 200 mmHg for 5 min
Liang 2021	China	R, OL	Hypertension	40	35.1	52.5	52.5	7.38	60 min, daily	Usual care	7	49	Forearm inflating to 200 mmHg for 5 min
Zhang 2021	China	R, OL	Stable CAD	102	66.8	52	NR	3.49	60 min, 6 days/week	Conventional therapy	6	36	Forearm inflating to 200 mmHg for 5 min
Wang 2022a	China	R, OL	UA	132	61.5	53.3	29.5	3.53	30 min, daily	Conventional therapy	7	24.5	Forearm inflating to 200 mmHg for 5 min
Zhang 2022	China	R, OL	Stable CAD	200	62.5	62.4	31	6.41	60 min, daily	Conventional therapy	3	21	Forearm inflating to 240 mmHg for 5 min
Wang 2022b	China	R, OL	Stable CAD	60	57	78.3	70	4.48	60 min, daily	Conventional therapy	5	35	Forearm inflating to 200 mmHg for 5 min
Lian 2022	China	R, OL	Stable CAD	125	60	68.8	60.8	7.32	30 min, twice daily	Conventional therapy	7	49	Forearm inflating to 200 mmHg for 5 min

FMD: flow-mediated dilation; EECP: enhanced external counterpulsation; MetS: metabolic syndrome; PCI: percutaneous coronary intervention; IGT: impaired glucose tolerance; CSPF: coronary slow flow phenomenon; UA: unstable angina; R: randomized; DB: double-blind; PC: placebo-controlled; OL: open-label; NR: not reported.

Table 2. Study quality evaluation via the Cochrane risk of bias Tool.

Study	Random sequence generation	Allocation concealment	Blinding in performance	Blinding in outcome detection	Incomplete outcome data	Reporting bias	Other bias
Wang 2006	Unclear	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Braith 2010	Unclear	Unclear	Low risk	Low risk	Low risk	Low risk	Low risk
Gloekler 2010	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Chen 2011	Unclear	Unclear	High risk	Low risk	Low risk	Low risk	Low risk
Martin 2012	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Xiao 2015	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Chen 2015	Unclear	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Zheng 2016	Unclear	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Jiang 2019	Unclear	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Liu 2019	Unclear	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Zhang 2019	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Tan 2019	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Qiao 2020	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Liang 2021	Unclear	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Zhang 2021	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Wang 2022a	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Zhang 2022	Low risk	Unclear	High risk	Low risk	Low risk	Low risk	Low risk
Wang 2022b	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Lian 2022	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk

Figure 2. Forest plots for the meta-analysis of the influence of EECP on brachial artery FMD. (A) Forest plots for the overall meta-analysis; and (B) Forest plots for the subgroup analysis in patients with CAD and other diseases.

Figure 3. Univariate meta-regression analyses for the correlation between FMD at baseline and the improvement of EECP on FMD.

Figure 4. Forest plots for the subgroup analyses of the influence of EECP on brachial artery FMD according to the baseline FMD levels.

Table 3. Univariate meta-regression analysis.

	MD of changes of FMD after treatment (%)
Covariate	Coefficient	95% CI	p
Patient number	0.0039	−0.0045 to 0.0124	0.34
Mean age (years)	−0.0025	−0.0572 to 0.0522	0.92
Men (%)	0.0073	−0.0348 to 0.0494	0.72
Mean FMD at baseline (%)	0.42	0.24 to 0.59	<0.001
Treatment duration (weeks)	0.021	−0.266 to 0.308	0.88
Accumulating hours on EECP	0.026	−0.013 to 0.065	0.18

FMD: flow-mediated dilation; MD: mean difference; CI: confidence interval; EECP: enhanced external counterpulsation.

Table 4. Summarized certainty of evidence using the GRADE system.

Outcome	Quality assessment							Absolute effect MD (95% CI)	Quality
	No. of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations
FMD (%)	19	RCTs	Serious	No serious inconsistency	No serious indirectness	No serious imprecision	None	1.96 (1.57–2.36)	⊕⊕⊕Ο MODERATE

GRADE: Grading of Recommendations, Assessment, Development and Evaluation; FMD: flow-mediated dilation; RCT: randomized controlled trials; MD: mean difference; CI: confidence interval.

Figure 5. Funnel plots for the publication bias underlying the meta-analysis of the influence EECP on brachial artery FMD.