Enteropathy and intestinal malabsorption in patients treated with antihypertensive drugs. A retrospective cohort study

Sae R. Lee; Eun G. Lee; Young H. Cho; Eun J. Park; Young-In Lee; Jung I. Choi; Ryuk-Jun Kwon; Soo M. Son; Sang Y. Lee; Yu H. Yi; Gyu L. Kim; Yun J. Kim; Jeong G. Lee; Young Jin Tak; Seung Hun Lee; Young Jin Ra

doi:10.15537/smj.2024.45.4.20230739

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Table 1

- Baseline characteristics and comorbidities according to antihypertensive drug.

Total	Age (years)	Male, n (%)	Prescription days, median (Q1, Q3)	Comorbidities, n (%)
Total	Age (years)	Male, n (%)	Prescription days, median (Q1, Q3)	Auto immune	Heart failure	Dementia	Diabetes	Cancer	CKD
ARBs (n=21,820)	63.1 ± 13.6^a	12,465 (57.1)	77 (14, 497)^a	168 (0.8)^a	1,542 (7.8)	727 (3.3)^a	5,271 (24.2)^a	1,469 (6.7)^a	2,657 (12.2)
Olmesartan (n=1,995)	63.6 ± 13.3^a,b	1,122 (56.2)^b,c,d	35 (7, 271)^d	10 (0.5)^a,b	118 (5.9)^a,b	70 (3.5)^a,b,c,d	375 (18.8)^b,c	174 (8.7)^g	207 (10.4)^d,e,f
Candesartan (n=6,650)	63.2 ± 13.4^a,b	4,036 (60.7)^a	94 (14, 713)^b	32 (0.5)^b	83 (12.5)^c	199 (3.0) ^a,b,c,d	1,723 (25.9)^a	357 (5.4)^e,f,h	797 (12.0)^f
Fimasartan (n=3,005)	63.7 ± 12.8^a,b	1,803 (60.0)^a,d	82 (15, 403)^a,b	16 (0.5)^a,b	86 (2.9)^d	128 (4.3)^c,d	570 (19.0)^b,c	127 (4.2)^h	153 (5.1)^c
Irbesartan (n=2,021)	63.4 ± 12.7^a,b	1,062 (52.5)^b,c	99 (21, 573)^b	10 (0.5)^a,b	72 (3.6)d	88 (4.4)^b,d	575 (28.5)^a	117 (5.8)^c,d,f,h	169 (8.4)^b,d
Losartan (n=3,300)	62.6 ± 15.6^a,b	1,750 (53.0)^b,c	56 (9, 405)^a,c	71 (2.2)	145 (4.4)^b,d	106 (3.2)^a,b,c,d	662 (20.1)^c	293 (8.9)^b,g	551 (16.7)^g,h
Telmisartan (n=2,030)	61.8 ± 13.4^a	1,118 (55.1)^b,c	49 (8, 407)^a,c	16 (0.8)^a,b	73 (3.6)^d	45 (2.2)^a,e	544 (26.8)^a	170 (8.4)^b,d,g	266 (13.1)^e,f,h
Valsartan (n=2,819)	63.4 ± 13.7^a,b	1,574 (55.8)^b,c,d	54 (10, 357)^a,c	23 (0.8)^a,b	332 (11.8)^c	91 (3.2)^a,b,c,d	822 (29.2)^a	231 (8.2)^b,d,g	514 (18.2)^g
ACEI (n = 1,297)	62.7 ± 14.5^a	843 (65.0)	67 (9, 470)^a	8 (0.6)^a	289 (22.3)	34 (2.6)^a,b	325 (25.1)^a	95 (7.3)^a	98 (7.6)
Ramipril (n = 1,297)	62.7 ± 14.5^a	843 (65.0)^a	67 (9, 470)^a	8 (0.6)^a,b	289 (22.3)	34 (2.6)^a,b,c,d	325 (25.1)^a	95 (7.3) ^{a,b,c,d,e,f,g}	98 (7.6)^a,b,c,d
CCB (n=6,769)	64.8 ± 13.2	3,523 (52.0)	22 (3, 175)	35 (0.5)^a	79 (1.2)	219 (3.2)^a	855 (12.6)	699 (10.3)	381 (5.6)
Amlodipine (n=6,769)	64.8 ± 13.2	3,523 (52.0)^c	22 (3, 175)	35 (0.5)^a,b	79 (1.2)	219 (3.2)^a,b,c,d	855 (12.6)	699 (10.3)^b,g	381 (5.6)^a,c
BBs (n=4,889)	54.3 ± 16.1	7,452 (50.1)	23 (1, 149)	115 (0.8)^a	359 (2.4)	252 (1.7)^b	1,488 (10.0)	541 (3.6)	350 (2.4)
Bisoprolol (n=4,284)	62.9 ± 14.4^a,b	2,424 (56.6)^b,d	31 (8, 306)^d	18 (0.4)^b	308 (7.2)^a	92 (2.1)^a	691 (16.1)^b	249 (5.8)^a,c,e,f,h	228 (5.3)^a,c
Propranolol (n=10,605)	50.8 ± 15.4	5,028 (47.4)	15 (1, 103)	97 (0.9)^a	51 (0.5)	160 (1.5)^e	797 (7.5)	292 (2.8)	122 (1.2)
Total (N= 44,775)	60.4 ± 15.1	24,283 (54.2)	35 (7, 312)	336 (0.8)	2,387 (5.3)	1,232 (2.8)	7,939 (17.7)	2,804 (6.3)	3,486 (7.8)

Values are mean ± SD (age), median (Q1, Q3) (prescription days), or number (%). The analysis was conducted separately for antihypertensive drug classes and individual antihypertensive drugs. The same superscript lowercase letters indicate no statistical significance between the groups being compared: ANOVA and Duncan’s post hoc test or Kruskall-Wallis H test and Duncan’s post hoc test for continuous variables and Chi-square test and Bonferrini’s post hoc test for categorical variables. ACEI: angiotensin-converting enzyme inhibitor, ARBs: angiotensin receptor blockers, CCB: calcium channel blocker, BBs: beta-blockers, CKD: chronic kidney disease

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Table 2

- Incidence of enteropathy and intestinal malabsorption according to antihypertension drug class and antihypertension drugs.

Antihypertensive drug classes			Antihypertension drugs
Classes	Incidence, n (%)	P-value^*	Drugs	Incidence, n (%)	P-value^*
Olmesartan (n=1,995)	3 (0.2)		Olmesartan (n=1,995)	3 (0.2)
Other ARBs (n=19,825)	22 (0.1)	0.620	Candesartan (n=6,650)	7 (0.1)	0.604
			Fimasartan (n=3,005)	4 (0.1)	0.873
			Irbesartan (n=2,021)	3 (0.2)	0.987
			Losartan (n=3,300)	5 (0.2)	0.992
			Telmisartan (n=2,030)	1 (0.1)	0.309
			Valsartan (n=2,819)	2 (0.1)	0.400
ACEI (n=1,297)	2 (0.2)	0.978	Ramipril (n=1,297)	2 (0.2)	0.978
CCB (n=6,769)	9 (0.1)	0.854	Amlodipine (n=6,769)	9 (0.1)	0.854
Beta-blockers (n=14,889)	15 (0.1)	0.524	Bisoprolol (n=4,284)	3 (0.1)	0.338
Beta-blockers (n=14,889)	15 (0.1)	0.524	Propranolol (n=10,605)	12 (0.1)	0.679
Total (N=44,775)	51 (0.1)		Total (N=44,775)	51 (0.1)

Values are presented as number (%). ACEI: angiotensin-converting enzyme inhibitor, ARBs: angiotensin receptor blockers, CCB: calcium channel blocker,

↵^* Fisher exact test

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Table 3

- Risk over time (descriptive data) and odds ratios of enteropathy or intestinal malabsorption over time according to antihypertensive drugs.

Drugs	PY	Number of events	Crude incidient rate (per 100,000 PY)	Crude ORs		Adjusted ORs^*
Drugs	PY	Number of events	Crude incidient rate (per 100,000 PY)	Value (95% CI)	P-value	Value (95% CI)	P-value
ACEI	523,850	2	0.38	Reference		Reference
ARBs	9,216,302	25	0.27	0.743 (0.176-3.137)	0.686	0.915 (0.525-1.595)	0.754
Olmesartan	527,739	3	0.57	0.975 (0.162-5.836)	0.978	1.131 (0.188-6.798)	0.893
Candesartan	3,559,887	7	0.20	0.683 (0.142-3.286)	0.634	0.621 (0.129-2.995)	0.553
Fimasartan	1,027,994	4	0.39	0.863 (0.158-4.713)	0.865	0.929 (0.170-5.079)	0.932
Irbesartan	992,926	3	0.30	0.963 (0.161-5.761)	0.967	0.910 (0.152-5.457)	0.918
Losartan	1,273,802	5	0.39	0.983 (0.191-5.064)	0.983	1.055 (0.204-5.443)	0.949
Telmisartan	880,282	1	0.11	0.319 (0.029-3.523)	0.351	0.326 (0.030-3.600)	0.360
Valsartan	953,672	2	0.21	0.460 (0.065-3.266)	0.438	0.493 (0.069-3.503)	0.479
Amlodipine	1,798,591	9	0.50	0.862 (0.186-3.991)	0.850	0.928 (0.200-4.307)	0.924
Beta-blokers	3,638,386	15	0.41	0.653 (0.149-2.857)	0.572	0.663 (0.151-2.906)	0.586
Propranolol	1,320,971	12	0.91	0.454 (0.076-2.718)	0.387	0.492 (0.082-2.948)	0.438
Bisoprolol	2,317,415	3	0.13	0.734 (0.164-3.279)	0.685	1.301 (0.285-5.949)	0.734

PY: person year, ACEI: angiotensin-converting enzyme inhibitor, ARBs: angiotensin receptor blockers, CCB: Calcium channel blocker, ORs: odds ratio, CI: confidence interval