The effect of carvedilol and propranolol on portal hypertension in patients with cirrhosis: a meta-analysis

Figures & data

Figure 1 Study flow diagram of the identification process of RCTs for inclusion in this meta-analysis.

Abbreviation: RCTs, randomized controlled trials.

Table 1 Characteristics of seven included studies

First author	Publication year	Study design	Sample size	No of patients C/P	Time of outcome assessment	No of patients with first/second HVPG measurement
						C	P
Bañares et al^Citation15	1999	RCT	28	14/14	Acute	14/14	14/14
Lin et al^Citation18	2004	RCT	22	11/11	Acute	11/11	11/11
Ren^Citation20	2012	RCT	61	30/31	Acute	30/30	31/31
Qu^Citation21	2012	RCT	54	25/29	Acute	25/25	29/29
De et al^Citation17	2002	RCT	36	18/18	Acute Long-term	18/18 18/17	18/18 18/16
Bañares et al^Citation16	2002	RCT	51	26/25	Long-term	26/24	25/22
Hobolth et al^Citation19	2012	RCT	38	21/17	Long-term	21/21	17/17

Abbreviations: No, number; C, carvedilol; P, propranolol; HVPG, hepatic vein pressure gradient; RCT, randomized controlled trial.

Table 2 Characteristics of patients in seven included studies

	Treatment group	Patients (N)	Age (mean ± SD)	Males (N)	Alcoholic/viral etiology (N)	Child-Pugh class A/B/C (N)	Previous variceal bleeding (N)
Bañares et al^Citation15	C	14	54.6±8.8	NM	8/NM	8/4/2	9
	P	14	51.4±8.5	NM	8/NM	5/6/3	9
Lin et al^Citation18	C	11	59±13.3	8	0/11	8.7±3.0a	NM
	P	11	61±13.3	9	0/11	7.3±2.7a	NM
Ren^Citation20	C	30	50.12±9.28	23	3/9	16/12/2	15
	P	31	52.93±13.06	21	2/21	22/7/2	18
Qu^Citation21	C	25	48.4±9.8	20	1/18	12/13/1	14
	P	29	53.7±12.9	20	3/17	9/17/2	16
De et al^Citation17	C	18	42.3±11.9	15	5/9	5/9/4	7
	P	18	47.3±12.9	17	10/5	0/13/5	7
Bañares et al^Citation16	C	26	57.9±7.6	19	6/18	13/10/3	0
	P	25	58.4±11	15	9/16	15/6/4	0
Hobolth et al^Citation19	C	21	58.2±6.8	12	2/18	8/7/6	5
	P	17	56.2±6.1	12	12/1	6/6/4	5

Note:

a Child-Pugh score, mean ± SD (derived from the standard error reported in the study).

Abbreviations: N, number; SD, standard deviation; C, carvedilol; NM, not mentioned; P, propranolol.

Figure 2 Risk of bias summary. Green dot, low risk; red dot, high risk; empty cell, unclear risk.

Table 3 Methodological quality assessment of included studies

	Random sequence generation	Allocation concealment	Blinding of participants and personnel	Blinding of outcome assessment	Incomplete outcome data	Selective reporting
Bañares et al^Citation15	Unclear risk	Unclear risk	Low risk	Low risk	Low risk	Low risk
Bañares et al^Citation16	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
De et al^Citation17 (acute)	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
De et al^Citation17 (long-term)	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Hobolth et al^Citation14	Unclear risk	Low risk	Low risk	Low risk	Low risk	Low risk
Lin et al^Citation18	Low risk	Unclear risk	Unclear risk	Unclear risk	Low risk	High risk
Ren^Citation20	Low risk	High risk	High risk	High risk	Low risk	Low risk
Qu^Citation21	Low risk	High risk	High risk	High risk	Low risk	Low risk

Table 4 Main results of the included studies

	Time of outcome assessment	Carvedilol			Propranolol
		HVPG baseline, mmHg (mean ± SDa)	%HVPG reduction (mean ± SDa)	Hemodyna respondersb mic (n/N)	HVPG baseline, mmHg (mean ± SDa)	%HVPG reduction (mean ± SDa)	Hemodynamic respondersb (n/N)
Bañares et al^Citation15	Acute	19.5±4.9	20.4±7.5	9/14	20.4±4.1	12.7±7.48	2/14
Lin et al^Citation18	Acute	18.9±6.0	18.6±11.9	NM	17.6±4.0	10.1±11.9	NM
Ren^Citation20	Acute	12.87±3.32	28.30±22.19	17/30	13.57±5.79	12.38±24.09	13/31
Qu^Citation21	Acute	12.89±3.27	26.43±22.77	15/25	12.88±5.17	1.45±34.58	9/29
De et al^Citation17	Acute	19.0±3.8	27.7±31.5	11/18	16.60±3.9	22.9±27.4	9/18
	Long-term	19.0±3.8	27.7±31.5	11/18	16.60±4.0	22.98±20.1	10/16
Bañares et al^Citation16	Long-term	19.1±5.4	19±9.8	13/24	20.3±4.2	12±9.4	5/22
Hobolth et al^Citation19	Long-term	17.6±4.2	19.3±16.1	13/21	18.4±3.6	12.5±16.7	7/17

Notes:

a SD: in the studies by Bañares et al^15,16 and by Lin et al¹⁸ the standard deviation of the mean was derived from the standard error of mean reported in the original studies.

b Hemodynamic responders were defined as patients whose HVPG reduction was ≥20% of baseline or ≤12 mmHg.

Abbreviations: HVPG, hepatic vein pressure gradient; SD, standard deviation; n/N, number; NM, not mentioned.

Figure 3 Subgroup analysis (fixed-effect model) of the percentage of hepatic vein pressure gradient reduction, representing the MDs (rectangles) and 95% CI (horizontal lines) for trials that compared carvedilol and propranolol.

Notes: The size of the rectangles indicates the weight of every trial. The above diamond shows the subtotal MD and 95% CI of the acute drug administration. The below diamond shows the subtotal MD and 95% CI of the long-term drug administration. The heterogeneity test is also performed.
Abbreviations: MD, mean difference; CI, confidence interval; SD, standard deviation; IV, inverse variance; HVPG, hepatic vein pressure gradient.

Figure 4 Subgroup analysis (fixed-effect model) of the percentage of hepatic vein pressure gradient reduction.

Notes: Subgroup analysis represents the MDs (rectangles) and 95% CI (horizontal lines) for trials that compared carvedilol and propranolol, excluding three trials with high-risk factor. The size of the rectangles indicates the weight of every trial. The above diamond shows the subtotal MD and 95% CI of the acute drug administration. The below diamond shows the subtotal MD and 95% CI of the long-term drug administration. The heterogeneity test is also performed.
Abbreviations: MD, mean difference; CI, confidence interval; SD, standard deviation; IV, inverse variance; HVPG, hepatic vein pressure gradient.

Figure 5 Subgroup analysis (fixed-effect model) of hemodynamic nonresponders, representing the RRs (rectangles) and 95% CI (horizontal lines) for trials that compared carvedilol and propranolol.

Notes: The size of the rectangles indicates the weight of every trial. The above diamond shows the subtotal RR and 95% CI of the acute drug administration. The below diamond shows the subtotal RR and 95% CI of the long-term drug administration. The heterogeneity test is also performed.
Abbreviations: RRs, risk ratios; CI, confidence interval; M–H, Mantel–Haenszel; HVPG, hepatic vein pressure gradient.

Figure 6 Subgroup analysis (fixed-effect model) of hemodynamic nonresponders.

Notes: Subgroup analysis represents the RRs (rectangles) and 95% CI (horizontal lines) for trials that compared carvedilol and propranolol excluding three studies with high-risk factor. The size of the rectangles indicates the weight of every trial. The above diamond shows the subtotal RR and 95% CI of the acute drug administration. The below diamond shows the subtotal RR and 95% CI of the long-term drug administration. The heterogeneity test is also performed.
Abbreviations: RRs, risk ratios; CI, confidence interval; M–H, Mantel–Haenszel; HVPG, hepatic vein pressure gradient.

Figure 7 Subgroup analysis (random-effect model) of the percentage of mean arterial pressure reduction, representing the MDs (rectangles) and 95% CI (horizontal lines) for trials that compared carvedilol and propranolol.

Notes: The size of the rectangles indicates the weight of every trial. The above diamond shows the subtotal MD and 95% CI of the acute drug administration. The below diamond shows the subtotal MD and 95% CI of the long-term drug administration. The heterogeneity test is also performed.
Abbreviations: MD, mean difference; CI, confidence interval; SD, standard deviation; IV, inverse variance; MAP, mean arterial pressure reduction.

Table 5 %MAP reduction of the included studies

	Time of outcome assessment	Carvedilol		Propranolol
		MAP baseline, mmHg (mean ± SDa)	%MAP reduction (mean ± SDa)	MAP baseline, mmHg (mean ± SDa)	%MAP reduction (mean ± SDa)
Bañares et al^Citation15	Acute	89±4	17.2±2.4	87±3	3.4±2.3
Lin et al^Citation18	Acute	95±4	11.3±2.9	94±3	8.9±2.2
Ren^Citation20	Acute	95.14±12.02	10.06±8.73	92.48±15.88	6.46±12.56
Qu^Citation21	Acute	93.65±13.16	9.09±8.65	90.41±17.02	3.63±15.76
De et al^Citation17	Acute	97.30±10.25	NM	91.90±16.03	NM
	Long-term	97.30±10.25	NM	91.90±16.03	NM
Bañares et al^Citation16	Long-term	91.4±2.5	11±1	88.6±4.5	5±3
Hobolth et al^Citation19	Long-term	97±13	5.1±14.9	98±8	8.2±12.5

Notes:

a In the studies by Bañares et al^15,16 and by Lin et al¹⁸ the standard deviation of the mean was derived from the standard error of the mean reported in the original studies.

Abbreviations: MAP, mean arterial pressure reduction; SD, standard deviation; NM, not mentioned.

Figure 8 MD (fixed-effect model) of the percentage of mean arterial pressure reduction (%MAP reduction) between carvedilol and propranolol in acute treatment trials, excluding one study with unclear risk. The heterogeneity test is also performed.

Abbreviations: MD, mean difference; MAP, mean arterial pressure; SD, standard deviation; IV, inverse variance; CI, confidence interval.

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