ObjectiveTo determine whether new users of proton pump inhibitors (PPIs) are at an increased risk of gastric cancer compared with new users of histamine-2 receptor antagonists (H2RAs).DesignUsing the UK Clinical Practice Research Datalink, we conducted a population-based cohort study using a new-user active comparator design. From 1 January 1990 to 30 April 2018, we identified 973 281 new users of PPIs and 193 306 new users of H2RAs. Cox proportional hazards models were fit to estimate HRs and 95% CIs of gastric cancer, and the number needed to harm was estimated using the Kaplan-Meier method. The models were weighted using standardised mortality ratio weights using calendar time-specific propensity scores. Secondary analyses assessed duration and dose–response associations.ResultsAfter a median follow-up of 5.0 years, the use of PPIs was associated with a 45% increased risk of gastric cancer compared with the use of H2RAs (HR 1.45, 95% CI 1.06 to 1.98). The number needed to harm was 2121 and 1191 for five and 10 years after treatment initiation, respectively. The HRs increased with cumulative duration, cumulative omeprazole equivalents and time since treatment initiation. The results were consistent across several sensitivity analyses.ConclusionThe findings of this large population-based cohort study indicate that the use of PPIs is associated with an increased risk of gastric cancer compared with the use of H2RAs, although the absolute risk remains low.
ObjectiveTo assess whether the use of dipeptidyl peptidase-4 inhibitors is associated with the incidence of inflammatory bowel disease in patients with type 2 diabetes.DesignPopulation based cohort study.SettingMore than 700 general practices contributing data to the United Kingdom Clinical Practice Research Datalink.ParticipantsA cohort of 141 170 patients, at least 18 years of age, starting antidiabetic drugs between 1 January 2007 and 31 December 2016, with follow-up until 30 June 2017.Main outcome measuresAdjusted hazard ratios for incident inflammatory bowel disease associated with use of dipeptidyl peptidase-4 inhibitors overall, by cumulative duration of use, and by time since initiation, estimated using time dependent Cox proportional hazards models. Use of dipeptidyl peptidase-4 inhibitors was modelled as a time varying variable and compared with use of other antidiabetic drugs, with exposures lagged by six months to account for latency and diagnostic delays.ResultsDuring 552 413 person years of follow-up, 208 incident inflammatory bowel disease events occurred (crude incidence rate of 37.7 (95% confidence interval 32.7 to 43.1) per 100 000 person years). Overall, use of dipeptidyl peptidase-4 inhibitors was associated with an increased risk of inflammatory bowel disease (53.4 v 34.5 per 100 000 person years; hazard ratio 1.75, 95% confidence interval 1.22 to 2.49). Hazard ratios gradually increased with longer durations of use, reaching a peak after three to four years of use (hazard ratio 2.90, 1.31 to 6.41) and decreasing after more than four years of use (1.45, 0.44 to 4.76). A similar pattern was observed with time since starting dipeptidyl peptidase-4 inhibitors. These findings remained consistent in several sensitivity analyses.ConclusionsIn this first population based study, the use of dipeptidyl peptidase-4 inhibitors was associated with an increased risk of inflammatory bowel disease. Although these findings need to be replicated, physicians should be aware of this possible association.
ObjectiveTo examine proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) prescribing patterns over a 29-year period by quantifying annual prevalence and prescribing intensity over time.DesignPopulation-based cross-sectional study.SettingMore than 700 general practices contributing data to the UK Clinical Practice Research Datalink (CPRD).ParticipantsWithin a cohort of 14 242 329 patients registered in the CPRD, 3 027 383 patients were prescribed at least one PPI or H2RA from 1 January 1990 to 31 December 2018.Primary and secondary outcome measuresAnnual prescription rates were estimated by dividing the number of patients prescribed a PPI or H2RA by the total CPRD population. Change in prescribing intensity (number of prescriptions per year divided by person-years of follow-up) was calculated using negative binomial regression.ResultsFrom 1990 to 2018, 21.3% of the CPRD population was exposed to at least one acid suppressant drug. During that period, PPI prevalence increased from 0.2% to 14.2%, while H2RA prevalence remained low (range: 1.2%–3.4%). Yearly prescribing intensity to PPIs increased during the first 15 years of the study period but remained relatively constant for the remainder of the study period. In contrast, yearly prescribing intensity of H2RAs decreased from 1990 to 2009 but has begun to slightly increase over the past 5 years.ConclusionsWhile PPI prevalence has been increasing over time, its prescribing intensity has recently plateaued. Notwithstanding their efficacy, PPIs are associated with a number of adverse effects not attributed to H2RAs, whose prescribing intensity has begun to increase. Thus, H2RAs remain a valuable treatment option for individuals with gastric conditions.
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