Proton pump inhibitors and all-cause mortality risk among cancer patients

Table 1 Demographic and clinical characteristics of patients with cancer by proton pump inhibitor use and non-users, n (%)/mean ± SD

Variables	Before the propensity score match			After the propensity score match
	PPI users (n = 48554)	Non-users (n = 2949116)	SMD	PPI users (n = 48452)	Non-users (n = 48452)	SMD
Age (years)	64.9 ± 12.2	62.4 ± 15.6	0.1803	64.9 ± 12.2	64.7 ± 12.8	0.0120
Sex (female)	20773 (428)	1494930 (50.67)	0.1590	20738 (42.8)	20146 (41.6)	0.0247
Ethnicity, Hispanic or Latino	2790 (5.7)	147470 (5.0)	0.0331	2785 (5.7)	2776 (5.7)	0.0008
Race
White	32556 (67.05)	1930606 (65.4)	0.0336	32507 (67.1)	32345 (66.7)	0.0071
Black or African American	7694 (15.8)	227813 (7.7)	0.2539	7643 (15.8)	7491 (15.5)	0.0086
Asian	737 (1.5)	88263 (2.9)	0.0995	737 (1.5)	442 (0.9)	0.0556
Others	6502 (13.4)	586750 (19.9)	0.1753	6500 (13.4)	7517 (15.5)	0.0597
Nicotine dependence	9974 (20.5)	129401 (4.4)	0.5044	9872 (20.4)	9991 (20.6)	0.0061
Alcohol dependence	2220 (4.6)	19796 (0.7)	0.2460	2144 (4.4)	1866 (3.8)	0.0288
BMI (kg/m2)	29 ± 6.64	28.1 ± 6.27	0.1473	29 ± 6.64	29.2 ± 6.73	0.0198
Cancer type
Digestive organs	3890 (8.0)	1852 (0.64)	0.3683	3855 (7.9)	436 (0.9)	0.3482
Thyroid and other endocrine glands	511 (1.0)	11107 (0.4)	0.0803	506 (1.0)	156 (0.3)	0.0878
Neuroendocrine tumors	157 (0.3)	3812 (0.1)	0.0409	156 (0.3)	111 (0.2)	0.0177
Ovary	176 (0.4)	3878 (0.1)	0.0465	176 (0.3)	52 (0.1)	0.0528
Cervix uteri	206 (0.42)	3150 (0.1)	0.0617	204 (0.4)	250 (0.1)	0.0622
Corpus uteri	298 (0.6)	6055 (0.2)	0.0640	297 (0.6)	113 (0.2)	0.0585
Breast	2561 (5.3)	56312 (1.9)	0.1816	2541 (5.2)	887 (1.8)	0.1856
Urinary tract	1725 (3.5)	13303 (0.4)	0.2228	1719 (3.5)	296 (0.6)	0.2069
Kidney	3 816 (7.85)	95657 (3.2)	0.2026	3767 (7.8)	3117 (6.4)	0.0522
Malignant neoplasm of bronchus and lung	4034 (8.3)	67074 (2.3)	0.2720	3988 (8.2)	3369 (6.9)	0.0482
Malignant melanoma	3507 (7.2)	50881 (1.7)	0.2683	3473 (7.2)	1018 (2.1)	0.2428
Prostate	1969 (4.0)	30803 (1.0)	0.1919	1946 (4.0)	548 (1.1)	0.1830
Others	24704 (50.8)	2567897 (86.1)	0.4367	26679 (55.1)	26899 (55.5)	0.0134
Comorbidities
Hypertension	21340 (43.9)	546208 (18.5)	0.5706	21238 (43.8)	21270 (43.9)	0.0013
Diabetes mellitus	10626 (219)	199682 (6.8)	0.4418	10529 (21.7)	10418 (21.5)	0.0056
Gastroesophageal reflux diseases	13540 (27.9)	126033 (4.3)	0.6788	13454 (27.8)	5132 (10.6)	0.4470
Peptic ulcers	1102 (2.3)	5925 (0.2)	0.1881	1051 (2.2)	374 (0.8)	0.1163
Gastroduodenitis	867 (1.8)	7790 (0.3)	0.1515	858 (1.8)	302 (0.6)	0.1057
Hyperlipidemia	14567 (30.0)	342093 (11.6)	0.4655	14480 (29.9)	13716 (28.3)	0.0347
Atrial fibrillation	4260 (8.8)	90521 (3.1)	0.2435	4228 (8.7)	3771 (7.8)	0.0343
Chronic lower respiratory diseases	11122 (22.9)	199314 (6.7)	0.4665	11021 (22.7)	10977 (22.6)	0.0022
Hypercholesterolemia	7075 (14.6)	174159 (5.9)	0.2888	7021 (14.5)	6663 (13.7)	0.0212
Cardiac arrhythmias	6421 (13.2)	107325 (3.6)	0.3502	6337 (13.1)	4982 (10.2)	0.0872
Coronary heart disease	3575 (7.4)	41413 (1.4)	0.2942	3513 (7.2)	2718 (5.6)	0.0669
Congestive heart failure	5089 (10.5)	63052 (2.1)	0.3483	5001 (10.3)	4704 (9.7)	0.0204
Cerebrovascular disease	6662 (13.7)	103190 (3.5)	0.3706	6570 (13.6)	6266 (12.9)	0.0185
Diabetic polyneuropathy	1983 (4.1)	26801 (1.0)	0.2046	1945 (4.0)	2082 (4.3)	0.0142
Glomerular diseases	770 (1.6)	8865 (0.3)	0.1333	752 (1.5)	564 (1.2)	0.0335
Chronic kidney disease	6790 (13.9)	114526 (3.9)	0.3598	6708 (13.8)	6350 (13.1)	0.0216
Peripheral vascular diseases	4220 (8.7)	53718 (1.8)	0.3116	4149 (8.6)	3444 (7.1)	0.0542
Diabetic retinopathy	981 (2.0)	16162 (0.5)	0.1311	958 (1.9)	1232 (2.5)	0.0381
Diabetic nephropathy	1789 (3.7)	25585 (0.868)	0.1897	1754 (3.6)	2040 (4.2)	0.0304
Diseases of pancreas	1761 (3.6)	15,072 (0.5)	0.2202	1740 (3.6)	673 (1.38)	0.1417
Diseases of gallbladder	928 (1.9)	9746 (0.3)	0.1506	915 (1.9)	545 (1.1)	0.0627
Diseases of biliary tract	1371 (2.8)	9373 (0.3)	0.2026	1349 (2.8)	535 (1.1)	0.1219
Cirrhosis of liver	2259 (4.6)	15246 (0.5)	0.2629	2224 (4.6)	1047 (2.2)	0.1348
Osteoporosis	3338 (6.9)	77419 (2.6)	0.2008	3318 (6.8)	2465 (5.1)	0.0744
Obstructive sleep apnea	4034 (8.3)	67074 (2.3)	0.2720	3988 (8.2)	3369 (6.9)	0.0482
Liver diseases	5502 (11.3)	58923 (2.0)	0.3810	5403 (11.1)	5334 (11.0)	0.0045
Cancer treatment
Chemotherapy	3922 (8.1)	112502 (3.8)	0.1810	3887 (8.0)	2419 (5.1)	0.1231
Antineoplastic and immunomodulating agents	7450 (15.3)	208407 (7.1)	0.2647	7400 (15.3)	4765 (9.8)	0.1647
Immunological agents	3816 (7.9)	95657 (3.2)	0.2026	3767 (7.8)	3117 (6.4)	0.0522
Radiotherapy	872 (1.8)	16379 (0.5)	0.1153	870 (1.8)	413 (0.8)	0.0826
Surgery	5480 (52.5)	769018 (26.1)	0.5615	25381 (52.4)	21120 (43.6)	0.1767
Targeted therapy	2092 (4.3)	9939 (0.3)	0.2660	2057 (4.2)	500 (1.0)	0.2015
Medications
Beta-blockers	14581 (30.0)	285348 (9.7)	0.5277	14490 (29.9)	10814 (22.3)	0.1734
Aspirin	13275 (27.3)	240151 (8.1)	0.5192	13179 (27.2)	10192 (21.0)	0.1445
NSAIDs usage	20915 (43.1)	464565 (15.7)	0.6286	20813 (42.9)	14519 (29.9)	0.2724
Hypoglycemic drugs	6495 (13.4)	123497 (4.2)	0.3290	6424 (13.2)	6558 (13.5)	0.0081
Insulin	6951 (14.3)	89333 (3.0)	0.4094	6849 (14.1)	6551 (13.5)	0.0178
Antiarrhythmics	6274 (33.5)	329864 (11.2)	0.5564	16179 (33.4)	11097 (22.9)	0.2348
Antilipemic agents	16154 (33.3)	358588 (12.1)	0.5206	16064 (33.1)	13083 (27.0)	0.1345
ACE inhibitors	10817 (22.3)	218846 (7.42)	0.4273	10744 (22.2)	8770 (18.1)	0.1017
Angiotensin II inhibitors	6268 (12.9)	137747 (4.7)	0.2941	6232 (12.8)	5092 (10.5)	0.0733
Diuretics	4023 (28.9)	269083 (9.1)	0.5204	13928 (28.7)	10575 (21.8)	0.1597
Vitamin D supplement	8317 (17.1)	150002 (5.1)	0.3905	8261 (17.0)	5233 (10.8)	0.1813
Vitamin E supplement	1318 (2.7)	30518 (1.0)	0.1241	1309 (2.7)	1033 (2.1)	0.0371
Calcium channel blockers	0519 (21.7)	190886 (6.4)	0.4477	10437 (21.5)	7842 (16.1)	0.1372
Antihypertensive combinations	171 (0.3)	2229 (0.1)	0.0599	168 (0.3)	197 (0.4)	0.0098
Opioids	1369 (2.8)	23224 (0.8)	0.1531	1359 (2.8)	678 (1.4)	0.0981
Immunosuppressants	1958 (4.0)	36586 (1.2)	0.1749	1945 (4.0)	1056 (2.2)	0.1061
Antiemetics	16473 (33.9)	320517 (10.9)	0.5755	16382 (33.8)	9934 (20.5)	0.3026
Antidepressants	11404 (23.5)	230648 (7.8)	0.4415	11331 (23.4)	7563 (15.6)	0.1972
Anticonvulsants	8945 (18.4)	139173 (4.7)	0.4386	8875 (18.3)	5306 (10.9)	0.2095
Laxatives	17542 (36.1)	295981 (10.0)	0.6512	17440 (35.9)	10634 (21.9)	0.3134

PPI: Proton pump inhibitor; SMD: Standard mean difference; BMI: Body mass index; NSAID: Non-steroidal anti-inflammatory drugs.

Table 2 Hazard ratios (95%CIs) for all-cause mortality between new users of proton pump inhibitors compared with non-users

Outcome	PPI-users (n = 48452)	Non-users (n = 48452)	HR (95%CI)
At 1 year	8888	3272	2.72 (2.61-2.83)
At 2 years	13719	5276	2.66 (2.58-2.74)
Overall outcome during follow-up	23421	11656	2.34 (2.29-2.42)

PPI: Proton pump inhibitor; HR: Hazard ratio.

Table 3 Hazard ratios (95%CIs) for all-cause mortality between new users of proton pump inhibitors compared to histamine 2 receptor antagonists in a secondary analysis

Outcome	PPI-users (n = 44834)	H2RA-users (n = 44834)	HR (95%CI)
At 1-year	8393	7980	1.51 (1.41-1.69)
At 2-years	12950	11989	1.16 (1.04-1.39)
Overall outcome during follow-up	18304	17146	1.17 (1.05-2.16)

PPI: Proton pump inhibitor; HR: Hazard ratio; H2RA: Histamine2 receptor antagonist.