Effect of angiotensin-converting enzyme inhibitors versus that of angiotensin receptor blockers on survival in patients undergoing hemodialysis: a nationwide observational cohort study

Figures & data

Table 1. Clinical characteristics of the patients.

	No (n = 49,982)	Other (n = 47,939)	ACEI (n = 40,003)	ARB (n = 49,927)	p
Age (years)	60.5 ± 0.1	60.7 ± 0.2	59.9 ± 0.6	60.3 ± 0.1	0.396
Sex (male, %)	29,136 (58.3%)	27,138 (57.3%)	24,494 (61.2%)	30,114 (60.3%)	0.093
Hemodialysis vintage (months)	51.6 ± 0.4	53.1 ± 0.9	51.2 ± 2.0	49.9 ± 0.4	0.136
Underlying causes of ESRD					0.254
Diabetes mellitus	21,526 (43.1%)	19,952 (42.1%)	18,626 (46.6%)	22,232 (44.5%)	–
Hypertension	13,200 (26.4%)	12,596 (26.6%)	10,604 (26.5%)	13,271 (26.6%)	–
Glomerulonephritis	5371 (10.7%)	5370 (11.3%)	3363 (8.4%)	5209 (10.4%)	–
Others	4331 (8.7%)	4187 (8.8%)	3317 (8.3%)	4028 (8.1%)	–
Unknown	5554 (11.1%)	5289 (11.2%)	4092 (10.2%)	5188 (10.4%)	–
CCI score	7.5 ± 0.0	7.6 ± 0.1	7.5 ± 0.1	7.5 ± 0.0	0.124
Type of vascular access					0.052
Arteriovenous fistula	42,384 (84.8%)	39,535 (83.4%)	34,744 (86.9%)	42,774 (85.7%)	–
Arteriovenous graft	7599 (15.2%)	7858 (16.6%)	5259 (13.1%)	7153 (14.3%)	–
Kt/Vurea	1.53 ± 0.00	1.53 ± 0.00	1.53 ± 0.01	1.53 ± 0.00	0.986
Ultrafiltration volume (L/session)	2.26 ± 0.01	2.29 ± 0.02	2.28 ± 0.04	2.26 ± 0.01	0.108
Hemoglobin (g/dL)	10.7 ± 0.0	10.7 ± 0.0	10.6 ± 0.0	10.6 ± 0.0	0.976
Serum albumin (g/dL)	3.98 ± 0.00	3.98 ± 0.01	3.98 ± 0.01	3.99 ± 0.00	0.912
Serum phosphorus (mg/dL)	5.0 ± 0.0	5.0 ± 0.0	5.0 ± 0.0	5.0 ± 0.0	0.848
Serum calcium (mg/dL)	8.9 ± 0.0	8.9 ± 0.0	8.9 ± 0.0	8.9 ± 0.0	0.211
Systolic blood pressure (mmHg)	140 ± 0	140 ± 0	141 ± 0	142 ± 0	0.579
Diastolic blood pressure (mmHg)	78 ± 0	78 ± 0	78 ± 0	78 ± 0	0.577
Serum creatinine (mg/dL)	9.4 ± 0.0	9.4 ± 0.0	9.4 ± 0.1	9.5 ± 0.0	0.353
Use of aspirin	21,069 (42.2%)	20,268 (42.8%)	18,090 (45.2%)	21,739 (43.5%)	0.239
Use of clopidogrel	8007 (16.0%)	8203 (17.3%)	7516 (18.8%)	8404 (16.8%)	0.135
Use of statins	14,510 (29.0%)	14,143 (29.8%)	13,030 (32.6%)	15,000 (30.0%)	0.129
MI or CHF	22,477 (45.0%)	22,294 (47.0%)	19,637 (49.1%)	22,948 (46.0%)	0.105

Data are expressed as mean ± standard error for continuous variables and as numbers (percentages) for categorical variables. p Values were tested using a survey-weighted generalized linear model.

ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin II receptor blocker; CCI: Charlson Comorbidity Index; CHF: congestive heart failure; ESRD: end-stage renal disease; MI: myocardial infarction

Figure 1. Kaplan–Meier curves of patient survival according to groups. The p values for pairwise comparison or trend with log-rank tests were added to the lower right corner of the graph. ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin II receptor blocker.

Table 2. Cox regression analyses for patient survival.

	Cohort before weighting				Cohort after weighting
	Univariate		Multivariable		Univariate		Multivariable
	HR (95% CI)	p	HR (95% CI)	p	HR (95% CI)	p	HR (95% CI)	p
Group
Ref: No
Other	1.24 (1.19–1.30)	<0.001	1.02 (0.97–1.08)	0.424	1.05 (1.03–1.07)	<0.001	1.03 (1.01–1.05)	0.028
ACEI	1.18 (1.05–1.31)	0.004	0.98 (0.86–1.11)	0.722	0.92 (0.91–0.95)	<0.001	0.94 (0.92–0.97)	<0.001
ARB	1.04 (1.01–1.07)	0.020	0.93 (0.89–0.96)	<0.001	0.98 (0.96–0.99)	0.040	0.96 (0.94–0.98)	0.001
Ref: Other
ACEI	0.95 (0.85–1.06)	<0.343	0.95 (0.83–1.09)	0.503	0.88 (0.86–0.90)	<0.001	0.92 (0.89–0.94)	<0.001
ARB	0.84 (0.80–0.87)	<0.001	0.90 (0.86–0.95)	<0.001	0.93 (0.91–0.95)	<0.001	0.94 (0.91–0.96)	<0.001
Ref: ACEI
ARB	0.88 (0.79–0.98)	0.023	0.95 (0.83–1.08)	0.415	1.06 (1.04–1.08)	<0.001	1.02 (0.99–1.05)	0.165
Age (increase per 1 year)	1.06 (1.06–1.06)	<0.001	1.06 (1.06–1.06)	<0.001	1.07 (1.06–1.07)	<0.001	1.06 (1.06–1.06)	<0.001
Sex (ref: male)	0.87 (0.84–0.89)	<0.001	0.74 (0.71–0.77)	<0.001	0.82 (0.81–0.84)	<0.001	0.74 (0.72–0.75)	<0.001
Underlying cause of ESRD (ref: DM)	0.81 (0.80–0.82)	<0.001	0.90 (0.88–0.91)	<0.001	0.81 (0.80–0.81)	<0.001	0.88 (0.88–0.89)	<0.001
Vascular access (ref: AVF)	1.52 (1.46–1.57)	<0.001	1.17 (1.12–1.23)	<0.001	1.45 (1.43–1.48)	<0.001	1.13 (1.10–1.16)	<0.001
HD vintage (increase per 1 month)	0.99 (0.99–1.00)	0.113	1.00 (1.00–1.01)	<0.001	0.99 (0.99–0.99)	<0.001	1.00 (1.00–1.01)	<0.001
CCI score (increase per 1 score)	1.14 (1.13–1.14)	<0.001	1.06 (1.05–1.07)	<0.001	1.13 (1.13–1.13)	<0.001	1.05 (1.05–1.06)	<0.001
UFV (increase per 1 kg/session)	0.91 (0.90–0.93)	<0.001	1.06 (1.04–1.09)	<0.001	0.91 (0.90–0.91)	<0.001	1.05 (1.04–1.06)	<0.001
KtVurea (increase per 1 unit)	0.91 (0.86–0.96)	<0.001	0.81 (0.75–0.88)	<0.001	0.87 (0.85–0.90)	<0.001	0.86 (0.82–0.89)	<0.001
Hemoglobin (increase per 1 g/dL)	0.86 (0.84–0.88)	<0.001	0.89 (0.87–0.91)	<0.001	0.88 (0.87–0.89)	<0.001	0.90 (0.89–0.91)	<0.001
Salb (increase per 1 g/dL)	0.37 (0.36–0.39)	<0.001	0.62 (0.59–0.66)	<0.001	0.34 (0.34–0.35)	<0.001	0.59 (0.57–0.61)	<0.001
Scr (increase per 1 mg/dL)	0.86 (0.86–0.87)	<0.001	0.94 (0.93–0.94)	<0.001	0.86 (0.86–0.86)	<0.001	0.94 (0.93–0.94)	<0.001
Sph (increase per 1 mg/dL)	0.85 (0.84–0.86)	<0.001	1.04 (1.02–1.05)	<0.001	0.84 (0.83–0.84)	<0.001	1.03 (1.02–1.04)	<0.001
Sca (increase per 1 mg/dL)	0.94 (0.92–0.95)	<0.001	1.06 (1.04–1.09)	<0.001	0.95 (0.94–0.95)	<0.001	1.08 (1.07–1.09)	<0.001
SBP (increase per 1 mmHg)	1.01 (1.01–1.01)	<0.001	1.01 (1.01–1.01)	<0.001	1.00 (1.00–1.01)	<0.001	1.01 (1.01–1.01)	<0.001
DBP (increase per 1 mmHg)	0.98 (0.98–0.99)	<0.001	1.00 (0.99–1.00)	0.070	0.98 (0.98–0.98)	<0.001	1.00 (0.99–1.00)	0.577
Use of aspirin	1.16 (1.13–1.19)	<0.001	0.96 (0.93–0.99)	0.019	1.16 (1.14–1.18)	<0.001	0.95 (0.93–0.96)	<0.001
Use of clopidogrel	1.54 (1.49–1.59)	<0.001	1.16 (1.11–1.21)	<0.001	1.55 (1.52–1.58)	<0.001	1.16 (1.13–1.18)	<0.001
Use of statins	1.08 (1.05–1.11)	<0.001	0.93 (0.90–0.97)	<0.001	1.11 (1.10–1.13)	<0.001	0.97 (0.95–0.99)	0.008
MI or CHF	1.51 (1.47–1.56)	<0.001	1.07 (1.03–1.11)	<0.001	1.48 (1.46–1.50)	<0.001	1.08 (1.06–1.10)	<0.001

Multivariate analysis was adjusted for age; sex; underlying cause of ESRD; vascular access; hemodialysis vintage; CCI score; ultrafiltration volume; Kt/V_urea; hemoglobin; serum albumin; serum creatinine; serum phosphorus; serum calcium levels; systolic blood pressure; diastolic blood pressure; use of statins, clopidogrel, and aspirin; MI or CHF and was performed using the enter mode.

ACEI: angiotensin converting enzyme inhibitor; ARB: angiotensin II receptor blocker; AVF: arteriovenous fistula; CCI: Charlson Comorbidity Index; CHF: congestive heart failure; ESRD: end–stage renal disease; CI: confidence interval; DBP: diastolic blood pressure; DM: diabetes mellitus; ESRD: end stage renal disease; HD: hemodialysis; HR: hazard ratio; MI: myocardial infarction; Salb: serum albumin; Sca: serum calcium; Scr: serum creatinine; Sph: serum phorphorus; SBP: systolic blood pressure; UFV: ultrafiltration volume

Table 3. Cox regression analyses using a competing risk model.

	Univariate		Multivariable
	HR (95% CI)	p	HR (95% CI)	p
Cohort before weighting
Ref: No
Other	1.24 (1.18–1.30)	<0.001	1.02 (0.96–1.08)	0.494
ACEI	1.16 (1.04–1.30)	0.008	0.97 (0.85–1.10)	0.629
ARB	1.04 (1.01–1.07)	0.018	0.93 (0.89–0.96)	<0.001
Ref: Other
ACEI	0.94 (0.84–1.05)	0.264	0.95 (0.83–1.09)	0.456
ARB	0.84 (0.80–0.88)	<0.001	0.91 (0.86–0.96)	<0.001
Ref: ACEI
ARB	0.89 (0.80–0.99)	0.043	0.96 (0.84–1.09)	0.506
Cohort after weighting
Ref: No
Other	1.05 (1.03–1.07)	<0.001	1.02 (0.99–1.04)	0.114
ACEI	0.93 (0.91–0.95)	<0.001	0.94 (0.91–0.96)	<0.001
ARB	0.98 (0.96–1.00)	0.055	0.96 (0.94–0.98)	<0.001
Ref: Other
ACEI	0.88 (0.86–0.90)	<0.001	0.92 (0.90–0.95)	<0.001
ARB	0.94 (0.92–0.95)	<0.001	0.94 (0.92–0.96)	<0.001
Ref: ACEI
ARB	1.06 (1.04–1.08)	<0.001	1.02 (0.99–1.05)	0.114

Multivariate analysis was adjusted for age; sex; underlying cause of end–stage renal disease; vascular access; hemodialysis vintage; Charlson comorbidity index score; ultrafiltration volume; Kt/V_urea; hemoglobin; serum albumin; serum creatinine; serum phosphorus; serum calcium levels; systolic blood pressure; diastolic blood pressure; use of statins, clopidogrel, and aspirin, myocardial infarction or congestive heart failure and was performed using the enter mode. Analyses using cohort after weights were performed using cohort after propensity score weights.

ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin II receptor blocker; CI: confidence interval; HR: hazard ratio

Data availability statement

The raw data were generated at the HIRA Service. The database can be requested from the HIRA Service by sending a study proposal including the purpose of the study, study design, and duration of analysis through an e-mail ([email protected]) or at the web site (https://www.hira.or.kr). The authors cannot distribute the data without permission.