Direct oral anticoagulant use and subsequent start of proton pump inhibitors as proxy for gastric complaints.
PURPOSE
Dabigatran use has been linked to gastrointestinal complaints, but it is unknown if this leads to more use of proton pump inhibitors (PPI). Furthermore, it is unknown whether gastrointestinal complaints occur more frequently in dabigatran users compared with other direct oral anticoagulant (DOACs) users. We investigated the association between DOAC use (dabigatran, rivaroxaban, or apixaban) and subsequent PPI initiation as a proxy for gastrointestinal complaints.


METHODS
In this population-based observational study with an active-comparator new user study design, anonymised dispensing data from Community Pharmacies in the Netherlands from 2012 to 2016 were used. Patients initiating DOAC for the treatment of atrial fibrillation without any PPI use before or at time of DOAC initiation were included. The outcome measure, subsequent PPI initiation, was determined in 28553 DOAC users.


RESULTS
The patients initiating dabigatran (10 942), apixaban (4897), or rivaroxaban (12714) were comparable for age (mean 69 years), sex (62% men), socioeconomic class, and concomitant medication use. The risk of PPI initiation in apixaban versus rivaroxaban users was similar (adjusted hazard ratio 1.06; 95% confidence interval 0.96-1.31) The adjusted hazard ratio of initiating PPI for dabigatran users was 1.21 (95% confidence interval 1.14-1.29) compared with rivaroxaban/apixaban users. The cumulative incidence of PPI initiation at 6 months of follow-up for patients using dabigatran was 13.0%, and 10.0% for those using rivaroxaban/apixaban, yielding a number needing treatment of 33.


CONCLUSIONS
Proton pump inhibitor initiation occurred frequently in incident DOAC users but more often in patients treated with dabigatran than in those treated with rivaroxaban or apixaban.
['Zielinski|G Denise|GD|0000-0003-1046-4055', 'Teichert|Martina|M|', 'Klok|Frederikus A|FA|', 'Rosendaal|Frits R|FR|', 'Huisman|Menno V|MV|', 'Cannegieter|Suzanne C|SC|', 'Lijfering|Willem M|WM|']
D000284:Administration, Oral D000368:Aged D000925:Anticoagulants D001281:Atrial Fibrillation D000069604:Dabigatran D011307:Drug Prescriptions D005260:Female D005767:Gastrointestinal Diseases D006801:Humans D015994:Incidence D008297:Male D008875:Middle Aged D009426:Netherlands D016016:Proportional Hazards Models D054328:Proton Pump Inhibitors D011720:Pyrazoles D011728:Pyridones D012307:Risk Factors D000069552:Rivaroxaban D020521:Stroke
anticoagulants proton pump inhibitors gastrointestinal atrial fibrillation risk pharmacoepidemiology