TY - JOUR
T1 - Long-term use of Proton Pump Inhibitors, Dose-response Relationship, and Associated Risk of Ischemic Stroke and Myocardial Infarction
AU - Sehested, Thomas S G
AU - Gerds, Thomas A
AU - Fosbøl, Emil L
AU - Hansen, Peter W
AU - Charlot, Mette G
AU - Carlson, Nicholas
AU - Hlatky, Mark A
AU - Torp-Pedersen, Christian
AU - Gislason, Gunnar H
N1 - © 2017 The Association for the Publication of the Journal of Internal Medicine.
PY - 2018
Y1 - 2018
N2 - Background: Use of proton pump inhibitors (PPIs) has been associated with cardiovascular disease amongst patients not on antiplatelet therapy. The associations of PPI use, duration and dose, with risk of first-time ischemic stroke and myocardial infarction (MI) are poorly understood. Methods: All Danish individuals with no prior history of MI or stroke, who had an elective upper gastrointestinal endoscopy performed between 1997 and 2012, were identified from nationwide registries. We used multiple Poisson regression to test associations with current PPI use and its dose and used multiple cause-specific Cox regression and g-formula methods to analyze long-term use. Results: Amongst 214 998 individuals, during a median follow-up of 5.8 years, there were 7916 ischemic strokes and 5608 MIs. Current PPI exposure was associated with significantly higher rates of both ischemic stroke (Hazard ratio (HR) 1.13; 95% confidence interval (CI) 1.08–1.19) and MI (HR 1.31, CI 1.23–1.39) after adjusting for age, sex, comorbidities and concomitant medication. High-dose PPI was associated with increased rates of ischemic stroke (HR 1.31, CI 1.21–1.42) and MI (HR 1.43, CI 1.30–1.57). Histamine H2 receptor antagonists (H2RAs) use was not significantly associated with ischemic stroke (HR 1.02, CI 0.84–1.24) or MI (HR 1.15, CI 0.92–1.43). Long-term users of PPIs, compared with nonusers, had a 29% (CI 5%-59%) greater absolute risk of ischemic stroke and a 36% (CI 7%-73%) greater risk of MI within a 6-month period. Conclusion: Use of PPIs was associated with increased risks of first-time ischemic stroke and MI, particularly amongst long-term users and at high doses.
AB - Background: Use of proton pump inhibitors (PPIs) has been associated with cardiovascular disease amongst patients not on antiplatelet therapy. The associations of PPI use, duration and dose, with risk of first-time ischemic stroke and myocardial infarction (MI) are poorly understood. Methods: All Danish individuals with no prior history of MI or stroke, who had an elective upper gastrointestinal endoscopy performed between 1997 and 2012, were identified from nationwide registries. We used multiple Poisson regression to test associations with current PPI use and its dose and used multiple cause-specific Cox regression and g-formula methods to analyze long-term use. Results: Amongst 214 998 individuals, during a median follow-up of 5.8 years, there were 7916 ischemic strokes and 5608 MIs. Current PPI exposure was associated with significantly higher rates of both ischemic stroke (Hazard ratio (HR) 1.13; 95% confidence interval (CI) 1.08–1.19) and MI (HR 1.31, CI 1.23–1.39) after adjusting for age, sex, comorbidities and concomitant medication. High-dose PPI was associated with increased rates of ischemic stroke (HR 1.31, CI 1.21–1.42) and MI (HR 1.43, CI 1.30–1.57). Histamine H2 receptor antagonists (H2RAs) use was not significantly associated with ischemic stroke (HR 1.02, CI 0.84–1.24) or MI (HR 1.15, CI 0.92–1.43). Long-term users of PPIs, compared with nonusers, had a 29% (CI 5%-59%) greater absolute risk of ischemic stroke and a 36% (CI 7%-73%) greater risk of MI within a 6-month period. Conclusion: Use of PPIs was associated with increased risks of first-time ischemic stroke and MI, particularly amongst long-term users and at high doses.
KW - myocardial infarction
KW - observational study
KW - proton pump inhibitors
KW - registries
KW - stroke
UR - http://www.scopus.com/inward/record.url?scp=85042268206&partnerID=8YFLogxK
U2 - 10.1111/joim.12698
DO - 10.1111/joim.12698
M3 - Journal article
C2 - 29024109
SN - 0954-6820
VL - 283
SP - 268
EP - 281
JO - Journal of Internal Medicine
JF - Journal of Internal Medicine
IS - 3
ER -