Association of short-term use of nonsteroidal anti-inflammatory drugs with stroke in patients with hypertension.
OBJECTIVE
Limited studies have investigated the risk of cerebrovascular events associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in subjects at high risk. We examined the short-term (defined as 30-day period) effect of selective and nonselective NSAIDs use on the risk of ischemic and hemorrhagic stroke in patients with hypertension.


METHODS
We conducted a case-crossover study using the National Health Insurance Research Database in Taiwan. We identified 1653 hypertensive subjects with stroke (defined as International Classification of Diseases-Ninth Revision-CM-codes: 433.x, 434.x, and 436.x for ischemic stroke; 430 and 431 for hemorrhagic stroke) in 2010. We investigated the transient effect of NSAIDs use on stroke using conditional logistic regressions with the adjustment of potential confounders.


RESULTS
The results suggested that NSAIDs use during the 30 days before stroke was associated with a 1.57-fold increased risk of ischemic stroke, but not of hemorrhagic stroke (adjusted odds ratio, 1.57; 95% confidence interval, 1.26-1.97 for ischemic stroke; and adjusted odds ratio, 1.38; 95% confidence interval, 0.79-2.40 for hemorrhagic stroke). When classifying NSAIDs into selective and nonselective groups, nonselective NSAIDs use significantly increased the risk of ischemic stroke (adjusted odds ratio, 1.55; 95% confidence interval, 1.24-1.94), but not of hemorrhagic stroke (adjusted odds ratio, 1.56; 95% confidence interval, 0.90-2.73).


CONCLUSIONS
The results demonstrate an increased risk of stroke, specifically ischemic stroke among hypertensive subjects with NSAIDs use. It would be important to closely monitor the transient effect of initial NSAIDs treatment, particularly in patients with hypertension.
From the Division of Preventive Medicine and Health Service Research (S.-Y.C.) and Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences (Y.-T.T., C.A.H., H.-J.T.), National Health Research Institutes, Zhunan, Miaoli County, Taiwan; Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China (Y.Y.); Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan (W.H.-H.S.); School of Medicine, National Yang-Ming University, Taipei, Taiwan (W.H.-H.S.); School of Medicine, National Defense Medical Center, Taipei, Taiwan (W.H.-H.S.); Mary Ann and J. Milburn Smith Child Health Research Program, Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, IL (X.L.); Department of Preventive Medicine (X.L.) and Department of Pediatrics (X.L., H.-J.T.), Feinberg School of Medicine, Northwestern University, Chicago, IL; and Department of Public Health, China Medical University, Taichung, Taiwan (H.-J.T.).
Shao-Yuan
SY
Chuang
From the Division of Preventive Medicine and Health Service Research (S.-Y.C.) and Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences (Y.-T.T., C.A.H., H.-J.T.), National Health Research Institutes, Zhunan, Miaoli County, Taiwan; Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China (Y.Y.); Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan (W.H.-H.S.); School of Medicine, National Yang-Ming University, Taipei, Taiwan (W.H.-H.S.); School of Medicine, National Defense Medical Center, Taipei, Taiwan (W.H.-H.S.); Mary Ann and J. Milburn Smith Child Health Research Program, Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, IL (X.L.); Department of Preventive Medicine (X.L.) and Department of Pediatrics (X.L., H.-J.T.), Feinberg School of Medicine, Northwestern University, Chicago, IL; and Department of Public Health, China Medical University, Taichung, Taiwan (H.-J.T.).
Yunxian
Y
Yu
From the Division of Preventive Medicine and Health Service Research (S.-Y.C.) and Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences (Y.-T.T., C.A.H., H.-J.T.), National Health Research Institutes, Zhunan, Miaoli County, Taiwan; Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China (Y.Y.); Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan (W.H.-H.S.); School of Medicine, National Yang-Ming University, Taipei, Taiwan (W.H.-H.S.); School of Medicine, National Defense Medical Center, Taipei, Taiwan (W.H.-H.S.); Mary Ann and J. Milburn Smith Child Health Research Program, Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, IL (X.L.); Department of Preventive Medicine (X.L.) and Department of Pediatrics (X.L., H.-J.T.), Feinberg School of Medicine, Northwestern University, Chicago, IL; and Department of Public Health, China Medical University, Taichung, Taiwan (H.-J.T.).
Wayne Huey-Herng
WH
Sheu
From the Division of Preventive Medicine and Health Service Research (S.-Y.C.) and Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences (Y.-T.T., C.A.H., H.-J.T.), National Health Research Institutes, Zhunan, Miaoli County, Taiwan; Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China (Y.Y.); Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan (W.H.-H.S.); School of Medicine, National Yang-Ming University, Taipei, Taiwan (W.H.-H.S.); School of Medicine, National Defense Medical Center, Taipei, Taiwan (W.H.-H.S.); Mary Ann and J. Milburn Smith Child Health Research Program, Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, IL (X.L.); Department of Preventive Medicine (X.L.) and Department of Pediatrics (X.L., H.-J.T.), Feinberg School of Medicine, Northwestern University, Chicago, IL; and Department of Public Health, China Medical University, Taichung, Taiwan (H.-J.T.).
Yu-Ting
YT
Tsai
From the Division of Preventive Medicine and Health Service Research (S.-Y.C.) and Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences (Y.-T.T., C.A.H., H.-J.T.), National Health Research Institutes, Zhunan, Miaoli County, Taiwan; Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China (Y.Y.); Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan (W.H.-H.S.); School of Medicine, National Yang-Ming University, Taipei, Taiwan (W.H.-H.S.); School of Medicine, National Defense Medical Center, Taipei, Taiwan (W.H.-H.S.); Mary Ann and J. Milburn Smith Child Health Research Program, Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, IL (X.L.); Department of Preventive Medicine (X.L.) and Department of Pediatrics (X.L., H.-J.T.), Feinberg School of Medicine, Northwestern University, Chicago, IL; and Department of Public Health, China Medical University, Taichung, Taiwan (H.-J.T.).
Xin
X
Liu
From the Division of Preventive Medicine and Health Service Research (S.-Y.C.) and Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences (Y.-T.T., C.A.H., H.-J.T.), National Health Research Institutes, Zhunan, Miaoli County, Taiwan; Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China (Y.Y.); Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan (W.H.-H.S.); School of Medicine, National Yang-Ming University, Taipei, Taiwan (W.H.-H.S.); School of Medicine, National Defense Medical Center, Taipei, Taiwan (W.H.-H.S.); Mary Ann and J. Milburn Smith Child Health Research Program, Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, IL (X.L.); Department of Preventive Medicine (X.L.) and Department of Pediatrics (X.L., H.-J.T.), Feinberg School of Medicine, Northwestern University, Chicago, IL; and Department of Public Health, China Medical University, Taichung, Taiwan (H.-J.T.).
Chao A
CA
Hsiung
From the Division of Preventive Medicine and Health Service Research (S.-Y.C.) and Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences (Y.-T.T., C.A.H., H.-J.T.), National Health Research Institutes, Zhunan, Miaoli County, Taiwan; Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China (Y.Y.); Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan (W.H.-H.S.); School of Medicine, National Yang-Ming University, Taipei, Taiwan (W.H.-H.S.); School of Medicine, National Defense Medical Center, Taipei, Taiwan (W.H.-H.S.); Mary Ann and J. Milburn Smith Child Health Research Program, Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, IL (X.L.); Department of Preventive Medicine (X.L.) and Department of Pediatrics (X.L., H.-J.T.), Feinberg School of Medicine, Northwestern University, Chicago, IL; and Department of Public Health, China Medical University, Taichung, Taiwan (H.-J.T.). tsaihj@nhri.org.tw.
Hui-Ju
HJ
Tsai
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002545:Brain Ischemia / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D020300:Intracranial Hemorrhages / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009313:National Health Programs / Q000706:statistics & numerical data; D018570:Risk Assessment; D020521:Stroke / Q000139:chemically induced* / Q000453:epidemiology / Q000209:etiology; D013624:Taiwan; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors
hypertension; pharmacoepidemiology; stroke