Adverse outcomes of long-term use of proton pump inhibitors: a systematic review and meta-analysis

Islam, Mohaimenul; Poly, Tahmina Nasrin; Walther, Bruno; Dubey, Navneet Kumar; Ningrum, Dina Nur Anggraini; Syed-Abdul, Shabbir; Li, Yu-Chuan

doi:10.1097/meg.0000000000001198

Cited by 67 publications

(58 citation statements)

References 121 publications

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“…Nevertheless, the list of potential side-effects related to long-term PPI use is increasing, including among others, chronic kidney disease, osteoporosis and fractures, Clostridium difficile infections, community acquired pneumonia, cardiac diseases, and even increased mortality [8][9][10][11][12][13][14][15][16][17][18][19]. An increasing number of studies have also investigated the risk of cancer with most evidence existing for gastric, colorectal and pancreatic cancer.…”

Section: Introductionmentioning

confidence: 99%

Long-term proton pump inhibitor usage and the association with pancreatic cancer in Sweden

2019

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Background The long-term safety of proton pump inhibitors (PPIs) is increasingly questioned. The aim of our study was to assess the risk of pancreatic cancer among longterm PPI users in Sweden. Methods This population-based nationwide Swedish cohort study including 796,492 adult long-term PPI users has been used to calculate the standardized incidence rate ratios (SIRs) and 95% confidence intervals (CI) for pancreatic cancer, stratifying by indications of use, age, sex, and duration of use. The risk among all 20,210 long-term H2-receptor antagonist users was assessed as comparison.Results Pancreatic cancer was found in 1733 long-term PPI users, and 25 H2-receptor antagonist users. For PPI users, the risk of pancreatic cancer was increased overall (SIRs = 2.22; 95% CI 2.12-2.32) and in all subgroup analyses, with the highest risk among PPI-users younger than 40 years (SIR = 8.90,, and among individuals with a history of Helicobacter pylori (SIR = 2.99, 95% CI 2.54-3.49). After the first year after enrolment (during which PPI use may be because of early symptoms of pancreatic cancer), the risk remained increased over time, with SIR = 1.57 (95% CI 1.38-1.76) after 5 years. No associations were found for H2-receptor antagonists (SIR = 1.02, 95% CI 0.66-1.51). Conclusions This large study showed an increased risk of pancreatic cancer in long-term users of PPIs in Sweden, in particular among the youngest users.

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Section: Introductionmentioning

confidence: 99%

Long-term proton pump inhibitor usage and the association with pancreatic cancer in Sweden

2019

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“…Simply being the reason for not including PPI risks on small‐intestinal injury or exacerbated nonsteroidal anti‐inflammatory drugs‐induced small intestinal injury. The meta‐analysis by Islam et al did not present the effects of PPIs on small‐intestinal bacterial overgrowth, spontaneous bacterial peritonitis, and enteric infections other than Clostridium difficile and gastric malignancies, which are presented in our paper.…”

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confidence: 63%

Response to Comment on ‘Proton Pump Inhibitors. Risks and Rewards and Emerging Consequences to the Gut Microbiome’

2018

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“…Long-term use of proton-pump inhibitors has been associated with adverse outcomes such as loss of bone-mineral density and increased occurrence of enteric and pulmonary infections. [18][19][20][21][22][23][24][25][26][27] Surgical or endoscopic proced ures to reduce reflux are done in selected medication-dependent or refractory cases. Health-care systems and individuals incur economic costs for physician visits, medications, and procedures.…”

Section: Introductionmentioning

confidence: 99%

The global, regional, and national burden of gastro-oesophageal reflux disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Dirac¹,

Safiri²,

Tsoi³

et al. 2020

The Lancet Gastroenterology & Hepatology

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Background Gastro-oesophageal reflux disease is a common chronic ailment that causes uncomfortable symptoms and increases the risk of oesophageal adenocarcinoma. We aimed to report the burden of gastro-oesophageal reflux disease in 195 countries and territories between 1990 and 2017, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Methods We did a systematic review to identify measurements of the prevalence of gastro-oesophageal reflux disease in geographically defined populations worldwide between 1990 and 2017. These estimates were analysed with DisMod-MR, a Bayesian mixed-effects meta-regression tool that incorporates predictive covariates and adjustments for differences in study design in a geographical cascade of models. Fitted values for broader geographical units inform prior distributions for finer geographical units. Prevalence was estimated for 195 countries and territories. Reports of the frequency and severity of symptoms among individuals with gastrooesophageal reflux disease were used to estimate the prevalence of cases with no, mild to moderate, or severe to very severe symptoms at a given time; these estimates were multiplied by disability weights to estimate years lived with disability (YLD). Findings Data to estimate gastro-oesophageal reflux disease burden were scant, totalling 144 location-years (unique measurements from a year and location, regardless of whether a study reported them alongside measurements for other locations or years) of prevalence data. These came from six (86%) of seven GBD super-regions, 11 (52%) of 21 GBD regions, and 39 (20%) of 195 countries and territories. Mean estimates of age-standardised prevalence for all locations in 2017 ranged from 4408 cases per 100 000 population to 14 035 cases per 100 000 population. Agestandardised prevalence was highest (>11 000 cases per 100 000 population) in the USA, Italy, Greece, New Zealand, and several countries in Latin America and the Caribbean, north Africa and the Middle East, and eastern Europe; it was lowest (<7000 cases per 100 000 population) in the high-income Asia Pacific, east Asia, Iceland, France, Denmark, and Switzerland. Global prevalence peaked at ages 75-79 years, at 18 820 (95% uncertainty interval [95% UI] 13 770-24 000) cases per 100 000 population. Global age-standardised prevalence was stable between 1990 and 2017 (8791 [95% UI 7772-9834] cases per 100 000 population in 1990 and 8819 [7781-9863] cases per 100 000 population in 2017, percentage change 0•3% [-0•3 to 0•9]), but all-age prevalence increased by 18

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Adverse outcomes of long-term use of proton pump inhibitors: a systematic review and meta-analysis

Cited by 67 publications

References 121 publications

Long-term proton pump inhibitor usage and the association with pancreatic cancer in Sweden

Long-term proton pump inhibitor usage and the association with pancreatic cancer in Sweden

Response to Comment on ‘Proton Pump Inhibitors. Risks and Rewards and Emerging Consequences to the Gut Microbiome’

The global, regional, and national burden of gastro-oesophageal reflux disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

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