TY - JOUR
T1 - Association of Proton Pump Inhibitor Use With All-Cause and Cause-Specific Mortality
AU - Lo, Chun Han
AU - Ni, Peiyun
AU - Yan, Yan
AU - Ma, Wenjie
AU - Joshi, Amit D.
AU - Nguyen, Long H.
AU - Mehta, Raaj S.
AU - Lochhead, Paul
AU - Song, Mingyang
AU - Curhan, Gary C.
AU - Cao, Yin
AU - Chan, Andrew T.
N1 - Funding Information:
Funding This work was supported by the National Institutes of Health ( UM1 CA186107 [Nurses’ Health Study cohort infrastructure grant], U01 CA167552 [Health Professionals Follow-up Study cohort infrastructure grant]; P30 CA091842 to Yan Yan; K23DK125838 to Long H. Nguyen; DK091417 to Gary C. Curhan; R35 CA253185 to Andrew T. Chan) and the Crohn’s and Colitis Foundation (Career Development Award and Research Fellowship Award to Long H. Nguyen). Andrew T. Chan is a Stuart and Suzanne Steele MGH Research Scholar and American Cancer Society Clinical Research Professor. The funders had no role in the design and conduct of the study. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.
Funding Information:
The authors would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention’s National Program of Cancer Registries and/or the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program. Central registries may also be supported by state agencies, universities, and cancer centers. Participating central cancer registries include the following: Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Idaho, Indiana, Iowa, Kentucky, Louisiana, Massachusetts, Maine, Maryland, Michigan, Mississippi, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Puerto Rico, Rhode Island, Seattle SEER Registry, South Carolina, Tennessee, Texas, Utah, Virginia, West Virginia, and Wyoming.
Funding Information:
Funding This work was supported by the National Institutes of Health (UM1 CA186107 [Nurses’ Health Study cohort infrastructure grant], U01 CA167552 [Health Professionals Follow-up Study cohort infrastructure grant]; P30 CA091842 to Yan Yan; K23DK125838 to Long H. Nguyen; DK091417 to Gary C. Curhan; R35 CA253185 to Andrew T. Chan) and the Crohn's and Colitis Foundation (Career Development Award and Research Fellowship Award to Long H. Nguyen). Andrew T. Chan is a Stuart and Suzanne Steele MGH Research Scholar and American Cancer Society Clinical Research Professor. The funders had no role in the design and conduct of the study. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.
Publisher Copyright:
© 2022 AGA Institute
PY - 2022
Y1 - 2022
N2 - Background & Aims: The use of proton pump inhibitors (PPIs) has increased rapidly in the past 2 decades. Concerns about the regular use of PPIs contributing to mortality have been raised. Methods: We conducted a prospective cohort study using data collected from the Nurses’ Health Study (2004–2018) and the Health Professionals Follow-up Study (2004–2018). Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for mortality according to PPI use. We used a modified lag-time approach to minimize reverse causation (ie, protopathic bias). Results: Among 50,156 women and 21,731 men followed for 831,407 person-years and a median of 13.8 years, we documented 22,125 deaths, including 4592 deaths from cancer, 5404 from cardiovascular diseases, and 12,129 deaths from other causes. Compared with nonusers of PPIs, PPI users had significantly higher risks of all-cause mortality (HR, 1.19; 95% CI, 1.13–1.24) and mortality due to cancer (HR, 1.30; 95% CI, 1.17–1.44), cardiovascular diseases (HR, 1.13; 95% CI, 1.02–1.26), respiratory diseases (HR, 1.32; 95% CI, 1.12–1.56), and digestive diseases (HR, 1.50; 95% CI, 1.10–2.05). Upon applying lag times of up to 6 years, the associations were attenuated and no longer statistically significant (all-cause: HR, 1.04; 95% CI, 0.97–1.11; cancer: HR, 1.07; 95% CI, 0.89–1.28; cardiovascular diseases: HR, 0.94; 95% CI, 0.81–1.10; respiratory diseases: HR, 1.20; 95% CI, 0.95–1.50; digestive diseases: HR, 1.38; 95% CI, 0.88–2.18). Longer duration of PPI use did not confer higher risks for all-cause and cause-specific mortality. Conclusions: After accounting for protopathic bias, PPI use was not associated with higher risks of all-cause mortality and mortality due to major causes.
AB - Background & Aims: The use of proton pump inhibitors (PPIs) has increased rapidly in the past 2 decades. Concerns about the regular use of PPIs contributing to mortality have been raised. Methods: We conducted a prospective cohort study using data collected from the Nurses’ Health Study (2004–2018) and the Health Professionals Follow-up Study (2004–2018). Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for mortality according to PPI use. We used a modified lag-time approach to minimize reverse causation (ie, protopathic bias). Results: Among 50,156 women and 21,731 men followed for 831,407 person-years and a median of 13.8 years, we documented 22,125 deaths, including 4592 deaths from cancer, 5404 from cardiovascular diseases, and 12,129 deaths from other causes. Compared with nonusers of PPIs, PPI users had significantly higher risks of all-cause mortality (HR, 1.19; 95% CI, 1.13–1.24) and mortality due to cancer (HR, 1.30; 95% CI, 1.17–1.44), cardiovascular diseases (HR, 1.13; 95% CI, 1.02–1.26), respiratory diseases (HR, 1.32; 95% CI, 1.12–1.56), and digestive diseases (HR, 1.50; 95% CI, 1.10–2.05). Upon applying lag times of up to 6 years, the associations were attenuated and no longer statistically significant (all-cause: HR, 1.04; 95% CI, 0.97–1.11; cancer: HR, 1.07; 95% CI, 0.89–1.28; cardiovascular diseases: HR, 0.94; 95% CI, 0.81–1.10; respiratory diseases: HR, 1.20; 95% CI, 0.95–1.50; digestive diseases: HR, 1.38; 95% CI, 0.88–2.18). Longer duration of PPI use did not confer higher risks for all-cause and cause-specific mortality. Conclusions: After accounting for protopathic bias, PPI use was not associated with higher risks of all-cause mortality and mortality due to major causes.
KW - Antacid
KW - Death
KW - Epidemiology
KW - GERD
KW - Medication
UR - http://www.scopus.com/inward/record.url?scp=85136085865&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2022.06.067
DO - 10.1053/j.gastro.2022.06.067
M3 - Article
C2 - 35788344
AN - SCOPUS:85136085865
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
ER -