Proton pump inhibitors and risk of all‐cause and cause‐specific mortality: A cohort study

Abstract

To investigate the association between proton pump inhibitors (PPIs) and both all-cause and cause-specific mortality.Methods: We conducted a cohort study using the UK Clinical Practice Research Datalink GOLD database. We compared 733 885 new users of PPIs to 124 410 new users of H2 receptor antagonists (H2Ras). In a secondary analysis we compared 689 602 PPI new users to 1 361 245 nonusers of acid suppression therapy matched on age, sex and calendar year. Hazard ratios for all-cause and cause-specific mortality were estimated using propensity score (PS) weighted Cox models.Results: PPI prescription was associated with increased risk of all-cause mortality, with hazard ratios decreasing considerably by increasing adjustment (unadjusted haz-

Protective effect of proton‐pump inhibitor against gastrointestinal bleeding in patients receiving oral anticoagulants: A systematic review and meta‐analysis

“…Other concerns that should be taken into account are PPI-associated adverse effects, such as acute kidney injury 68 that could alter the concentration of OAC, an increased risk of GI infections, 69,70 and mortality. 71,72 Therefore, clinicians should arouse vigilance of (long-term) PPI use with appropriate patient selection.…”

Proton Pump Inhibitor Therapy for Eosinophilic Esophagitis: History, Mechanisms, Efficacy, and Future Directions

“…143 There have been numerous meta-analyses for standard dose PPI therapy citing both associations and lack of association of PPI use and pneumonia, 144–148 other enteric infections, 149–151 gastric atrophy and cancer, 152–154 chronic kidney disease, 155–159 diabetes, 160 , 161 chronic obstructive lung disease, 162 , 163 dementia, 164–169 cardiovascular disease or cardiovascular events, 170–175 and all-cause mortality. 176–180 However, it is likely that most of the reported potential risks are due to residual confounding within the study design, 180–183 and a large-scale, industry sponsored randomized controlled trial recently emphasized the safety of this medication class and refuted most of the prior proposed associations. 176 FDA PPI package labeling does not address high dose twice daily therapy for EoE (not an FDA approved indication), and the lowest dose and shortest duration of PPI therapy are general prescribing recommendations.…”

Possible Association between the Use of Proton Pump Inhibitors and H2 Receptor Antagonists, and Esophageal Cancer: A Nested Case–Control Study Using a Korean National Health Screening Cohort

“…Earlier observational studies and meta-analyses appear to emphasize the cancer-protective effect of PPIs that prevents the progression to esophageal cancer [ 21 , 22 , 23 ], of which the vast majority were implemented in Western countries, including the United States, Europe, and Australia, focusing on the Barrett esophagus, with insufficiently matched control groups [ 7 , 21 , 22 , 23 , 24 ]. On the other hand, current epidemiological studies more likely indicate an increased probability of incident esophageal cancers following the use of PPIs [ 10 , 11 , 12 , 13 , 14 , 15 ]. One large Swedish population-based study shows that the risk for esophageal cancers is increased, irrespective of the length of PPI administration, through a cohort of nearly 800,000 patients taking PPIs [ 11 ].…”

“…In terms of medication factors, proton pump inhibitors (PPIs) and H 2 -receptor antagonists (H2RA) are commonly prescribed acid-suppressive agents worldwide and the standard treatment for upper gastrointestinal disease [ 9 ]. Although these drugs are considered safe, there has been a safety concern that the use of acid-suppressive medication might increase the risk for esophageal cancers [ 10 , 11 , 12 , 13 , 14 , 15 ]. The most preferred rationale for this theory is that PPI-induced hypergastrinemia may stimulate downstream signaling and promote cell proliferation and may actually lead to implications for esophageal cancer risk [ 16 , 17 ].…”