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Proton pump inhibitors may up risk of first-time ischaemic stroke

14 Aug 2017

Use of proton pump inhibitors (PPIs) appears to pose an increased risk of first-time ischaemic stroke in the general population, irrespective of treatment with antiplatelet agents, according to a study. However, the magnitude of the said association is modest, and a cause-and-effect relationship remains to be established.

The retrospective nationwide study drew data from the Taiwan National Health Insurance database. A total of 198,148 PPI users (mean age 51.7 years; 53.6 male) aged ≥20 years and a similar number of propensity score-matched non-PPI user controls were included. None of the participants had prior stroke or hospitalization before the index date.

Hospitalization with a primary diagnosis of ischaemic stroke during 120-day follow-up was the main study outcome. Analyses were performed using multivariate logistic regression, Cox proportional hazards, Kaplan–Meier method, log-rank test and conditional logistic regression (for the nested case–control analysis).

Results revealed that PPI use was associated with a 36-percent increase in the risk of hospitalization due to ischaemic stroke (hazard ratio, 1.36; 95 percent CI, 1.14 to 1.620; p=0.001). On subgroup analysis, susceptibility to the risk was highest among patients aged <60 years (p=0.043 for interaction), whereas factors such as gender, history myocardial infarction, diabetes mellitus, hypertension, use of antiplatelet agents or nonsteroidal anti-inflammatory drugs, or type of PPIs had no effect on the risk.

In the nested case–control analysis comparing 15,378 patients hospitalized due to ischaemic stroke with 15,378 matched controls, an association between PPI use and increased cerebrovascular risks was observed. The adjusted odds ratios for PPI use were 1.77 (1.45 to 2.18; p<0.001) within 30 days, 1.65 (1.31 to 2.08; p<0.001) between 31 and 90 days, and 1.28 (1.03 to 1.59; p=0.025) between 91 and 180 days prior to the onset of first-time ischaemic stroke.

The current finding of a PPI-associated increased risk of first-time ischaemic stroke should better be viewed as providing some clues for hypothesis generation rather than providing practical implications, researchers noted.

“Besides, the mechanisms underlying such an association are not clear, and the biological plausibility of the recently proposed asymmetric dimethylarginine (ADMA) hypothesis [suggesting that PPIs could increase the plasma levels of ADMA] which is a risk factor for cardiovascular events is yet to be tested,” they added.

Further research is needed to verify the present data.

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