Neumonía y consumo de fármacos supresores de la acidez gástricaestudio caso-control anidado en la cohorte poblacional de la Base de Datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP)

Abstract

Objectives: The main objective of this study was to assess the association between Community Acquired Pneumonia (CAP) and the exposure to gastric acid suppressive drugs (GASD) (Proton Pump Inhibitors (PPI) and H2-receptor antagonists (H2RAs)). Secondary objectives were: 1. To estimate the incidence rate (IR) of CAP in Spain and to compare it with the IR from United Kingdom; 2. To know the CAP patients’ hospitalization rate in Spain and to compare it with the rate from United Kingdom; 3. To analyze the use pattern of GASD and other drugs in Spain, and to compare with the pattern from United Kingdom and with the Spanish National Health Survey 2006 (ENS-06); 4. To analyze the prevalence of different pathologies in Spain with BIFAP and to compare with those of the United Kingdom and with those obtained within the ENS-06. Methods: Source of information: Primary healthcare database BIFAP. Other sources used for results comparison were the primary healthcare database THIN (TheHealth Improvement Network) and the ENS-06. Design: Observational retrospective after authorisation study. Nested case-control study in the cohort that is collected prospectively in the database of primary healthcare BIFAP. Study Period: From 1 January 2003 until 31 December 2007. Study Population: Subjects between 20 and 79 years old with no past history of pneumonia and with at least two years registration in the database. Patients with cancer or AIDS were excluded. All these patients were followed until occurrence of a pneumonia episode, death, age of 80, or the end of the study, whichever came first. Case definition and validation: Firstly, a computerized search was performed to detect suggestive cases of pneumonia. (by International Classification of Primary Care (ICPC) codes or free text). This was followed by a manual review of all identified cases, accomplished by two evaluators that classified the cases in one of these three categories: cases, doubtful or no cases. Prevalent cases, hospital-acquired pneumonias, and chemical or aspiration pneumonias, were excluded. The date of pneumonia diagnosis was considered as the index date. Controls selection: Controls were randomly sampled from the person-time experience of the study cohort. Furthermore, controls were matched to cases based on sex, age, and index date. Index date was a randomly date within the study period. Exposure definition: Any patient receiving a prescription within the 30 days time-window was considered exposed (current user). Recent use described a prescription that ended between 31 and 90 days before the index date. Past use was defined as a prescription ending between 91 days and one year before the index date. Finally, non-use was defined as no prescription in the year before the index date. Information of other variables was extracted from BIFAP database. Analysis: IR of pneumonia was computed by age, sex and season. To better estimate the risk associated with drug exposure, we performed a nested case-control analysis using logistic regression and adjusting to other potential confounders. Results: IR of CAP was 2.69 per 1000 persons-year (IR women=2.29; IR men=3.16) with BIFAP database. 32 % of the CAP cases were hospitalized. The incidence in Spain was higher than in United Kingdom using THIN database. CAP was associated with current use of PPIs (OR: 1.22; 95% confidence interval [CI]:1.12–1.33) but not H2RAs (OR: 1.06; IC95%: 0.86-1.32). These results coincide with that obtained in the study performed with THIN. Nevertheless, no clear duration response was observed with PPIs treatment and CAP. Although dose response was not observed with PPIs, people using high or medium dose had an increased risk of pneumonia. Among patients taking acid-suppressive drugs during less than one year, current use of PPIs was associated with community-acquired pneumonia only for patients treated for gastroesophageal reflux disease (GERD) (OR: 1.4; 95%CI: 1,11-1,77) or for prevention of upper gastrointestinal injury (OR: 1,28; 95%CI: 1,11-1,47). The latter results differ from those obtained in the study of THIN. Finally we analyzed the consumption pattern of different drugs and the prevalence of diverse diseases using the information obtained s from this study controls. The results were compared with the information of the controls of the study performed with THIN database and with the information of the ENS-06. Conclusions: Current users of PPIs associate an increased risk of CAP, but this association has not been detected in the group of consumers of H2RAs. Although the results are in agreement with other published studies, we can not affirm yet that this relation is causal. The present study confirms, once again, the validity of BIFAP as an efficient source of information to perform epidemiological studies and to respond to the new demands imposed by pharmacovigilance.