Community acquired pneumonia incidence before and after proton pump inhibitor prescription: population based study

Abstract

Objective To examine the risk of community acquired pneumonia before and after prescription of proton pump inhibitor (PPI) and assess whether unmeasured confounding explains this association.Design Cohort study and self controlled case series.Setting Clinical Practice Research Datalink (1990 to 2013) in UK.Participants Adult patients with a new prescription for a PPI individually matched with controls.Main outcome measures Association of community acquired pneumonia with PPI prescription estimated by three methods: a multivariable Cox model comparing risk in PPI exposed patients with controls, corrected for potential confounders; a self controlled case series; and a prior event rate ratio (PERR) analysis over the 12 month periods before and after the first PPI prescription.Results 160 000 new PPI users were examined. The adjusted Cox regression showed a risk of community acquired pneumonia 1.67 (95% confidence interval 1.55 to 1.79) times higher for patients exposed to PPI than for controls. In the self controlled case series, among 48 451 PPI exposed patients with a record of community acquired pneumonia, the incidence rate ratio was 1.19 (95% confidence interval 1.14 to 1.25) in the 30 days after PPI prescription but was higher in the 30 days before a PPI prescription (1.92, 1.84 to 2.00). The Cox regressions for prior event rate ratio similarly showed a greater increase in community acquired pneumonia in the year before than the year after PPI prescription, such that the analysis showed a reduced relative risk of pneumonia associated with PPI use (prior event rate ratio 0.91, 95% confidence interval 0.83 to 0.99).Conclusion The association between the use of PPIs and risk of community acquired pneumonia is likely to be due entirely to confounding factors.

A Multicenter, Prospective, Observational Study to Determine Predictive Factors for Multidrug‐Resistant Pneumonia in Critically Ill Adults: The DEFINE Study

“…An interesting finding of this study was the association between acid‐suppressive therapy and MDRO pneumonia. The role of proton‐pump inhibitor therapy in contributing to pneumonia has been documented previously . The findings of this study expand on previous findings by suggesting that acid‐suppressive therapy is an independent predictor of pneumonia due to an MDRO.…”

Elevated Potassium Levels in Patients With Congestive Heart Failure: Occurrence, Risk Factors, and Clinical Outcomes

“…Second, to study hyperkalemia impact in a subcohort more likely to have chronic HF, and thus be more closely followed up, patients who were alive at 6 months after HF discharge had an echocardiography performed and were treated with both ARBs or ACEis and β blocker up to this date were separately examined. Third, as an alternative method to account for remaining unmeasured confounding when comparing outcomes in patients with and without hyperkalemia with HF, the ratio of the 2 matched HRs observed after versus before the hyperkalemia/index date (ie, the prior event rate ratio adjusted rate ratio) was estimated . This method is based on the assumption that differences in outcomes between hyperkalemia‐exposed and matched hyperkalemia‐unexposed patients present already before experiencing hyperkalemia reflect the combined effect of remaining unmeasured confounders, independent of any effect of hyperkalemia.…”

Proton‐Pump Inhibitors and Long‐Term Risk of Community‐Acquired Pneumonia in Older Adults

“…Several studies, including meta‐analyses, have reported high risk of pneumonia soon after PPI therapy initiation, although negative associations have also been reported . A recent observational study of the first year after PPI prescription used the prior event rate ratio (PERR), which adjusts differences in postprescription pneumonia incidence between cases and controls with preexisting differences to correct for unmeasured confounding. That study used data from individuals in primary care in England and found that pneumonia rates increased during the first 30 days of PPI prescription (incidence rate ratio (IRR)=1.19, 95% confidence interval (CI)=1.14–1.25), but pneumonia rates were even higher during the 30 days immediately before the first PPI prescription (IRR=1.92, 95% CI=1.84–2.00), perhaps because the greater medical scrutiny of individuals with pneumonia led to more PPI prescribing for comorbidities, including medications commonly co‐prescribed with PPIs.…”