Objective: The aim of this study was to investigate the associations between proton pump inhibitor (PPI) usage patterns and risk of severe gastrointestinal events in patients treated with low-dose acetylsalicylic acid (LDA).
Design and setting: A nationwide cohort study in Sweden.
Patients: All Swedish residents ≥ 40 years of age, without cancer and receiving LDA treatment (≥ 80% adherence for 365 days between 2005 and 2009) were identified in the Swedish Prescription Register. Continuous PPI use was defined as > 60 of 90 days covered by daily PPI doses and further divided into high (≥ 80%) or moderate (< 80) adherence. All other PPI use was defined as intermittent use.
Main outcome measures: The risk of a combined end-point of gastrointestinal ulcer or bleeding was analysed using Cox proportional hazard models. We also investigated risk of > 45 days of LDA treatment interruption.
Results: During a median follow-up of 2.5 years, 7880 of 648,807 (1.2%) LDA-treated patients experienced gastrointestinal events. In multivariable-adjusted models, both intermittent-PPI and no-PPI use were associated with increased risk of gastrointestinal ulcers or bleeding compared with continuous PPI use with a high level of adherence [hazard ratio (HR) 1.83 (95% CI 1.66-2.02) and 1.14 (95% CI 1.05-1.23), respectively]. Amongst continuous PPI users, moderate adherence also increased the risk of gastrointestinal ulcers or bleeding [HR 1.22 (95% CI 1.07-1.40)]. The risk of LDA treatment interruption was higher with intermittent PPI use [HR 1.16 (95% CI 1.14-1.19)] than continuous PPI use with high adherence.
Conclusions: In this large cohort of LDA users, intermittent PPI use was associated with higher risk of gastrointestinal ulcers or bleeding and interrupted LDA treatment, compared with continuous PPI use.
Keywords: acetylsalicylic acid; medication adherence; peptic ulcer; prophylaxis; proton pump inhibitors.
© 2013 The Association for the Publication of the Journal of Internal Medicine.