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Emulating a target trial of proton pump inhibitors and dementia risk using claims data
Author(s) -
Ahn Nayeon,
Nolde Michael,
Günter Alexander,
Güntner Florian,
Gerlach Roman,
Tauscher Martin,
Amann Ute,
Linseisen Jakob,
Meisinger Christa,
RückertEheberg InaMaria,
Baumeister SebastianEdgar
Publication year - 2022
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.15284
Subject(s) - dementia , medicine , hazard ratio , confidence interval , vascular dementia , incidence (geometry) , proportional hazards model , disease , physics , optics
Background and purpose Understanding the adverse effects of proton pump inhibitors (PPIs) is important due to their widespread use, but the available evidence for an increased dementia risk amongst patients taking PPIs is inconclusive. The present study aimed to estimate the causal effect of PPIs on the risk of dementia by target trial emulation and time‐varying exposure modeling. Methods Using claims data of 2,698,176 insured people of a large German statutory health insurer, a target trial was conceptualized in which individuals aged 40 years and older were classified as PPI initiators or non‐initiators between 2008 and 2018, and were followed until diagnosis of dementia, death, loss to follow‐up or end of study. Incidence of dementia (International Classification of Diseases 10 codes F00, F01, F03, F05.1, G30, G31.0, G31.1, G31.9 and F02.8+G31.82) was defined applying a 1‐year lag window. Weighted Cox models were used to estimate the effect of PPI initiation versus non‐initiation on dementia risk and weighted pooled logistic regression was used to estimate the effect of time‐varying use versus non‐use. Results In all, 29,746 PPI initiators (4.4%) and 26,830 non‐initiators (1.3%) were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio for dementia was 1.54 (95% confidence interval 1.51–1.58). The hazard ratio for time‐dependent PPI use versus non‐use was 1.56 (95% confidence interval 1.50–1.63). Differentiated subtypes, including unspecified dementia, Alzheimer's disease and vascular dementia, showed increased risk by PPI initiation and time‐varying PPI use. Conclusions This study suggests that PPI initiation and time‐varying PPI use may increase overall dementia risk.