Chia-Hsuin Chang1, Chin-Hsien Lin1, James L Caffrey1, Yen-Chieh Lee1, Ying-Chun Liu1, Jou-Wei Lin2, Mei-Shu Lai1. 1. From Department of Internal Medicine, National Taiwan University Hospital, Taipei (C.-H.C.); Department of Medicine, College of Medicine, National Taiwan University, Taipei (C.-H.C., J.-W.L.); Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei (C.-H.C., Y.-C. Lee, Y.-C. Liu, M.-S.L.); Department of Neurology, National Taiwan University Hospital, Taipei (C.-H.L.); Department of Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth (J.L.C.); Department of Family Medicine, Cathay General Hospital, Taipei, Taiwan (Y.-C. Lee); and Cardiovascular Center, National Taiwan University Hospital Yun-Lin Branch, Dou-Liou City, Yun-Lin County (J.-W.L.). 2. From Department of Internal Medicine, National Taiwan University Hospital, Taipei (C.-H.C.); Department of Medicine, College of Medicine, National Taiwan University, Taipei (C.-H.C., J.-W.L.); Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei (C.-H.C., Y.-C. Lee, Y.-C. Liu, M.-S.L.); Department of Neurology, National Taiwan University Hospital, Taipei (C.-H.L.); Department of Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth (J.L.C.); Department of Family Medicine, Cathay General Hospital, Taipei, Taiwan (Y.-C. Lee); and Cardiovascular Center, National Taiwan University Hospital Yun-Lin Branch, Dou-Liou City, Yun-Lin County (J.-W.L.). jouweilin@yahoo.com.
Abstract
BACKGROUND: Reports of statin usage and increased risk of intracranial hemorrhage (ICH) have been inconsistent. This study examined potential associations between statin usage and the risk of ICH in subjects without a previous history of stroke. METHODS AND RESULTS: Patients initiating statin therapy between 2005 and 2009 without a previous history of ischemic or hemorrhagic stroke were identified from Taiwan's National Health Insurance database. Participants were stratified by advanced age (≥70 years), sex, and diagnosed hypertension. The outcome of interest was hospital admission for ICH (International Classification of Diseases, Ninth Revision, Clinical Modification codes 430, 431, 432). Cox regression models were applied to estimate the hazard ratio of ICH. The cumulative statin dosage stratified by quartile and adjusted for baseline disease risk score served as the primary variable using the lowest quartile of cumulative dosage as a reference. There were 1 096 547 statin initiators with an average follow-up of 3.3 years. The adjusted hazard ratio for ICH between the highest and the lowest quartile was nonsignificant at 1.06 with a 95% confidence interval spanning 1.00 (0.94-1.19). Similar nonsignificant results were found in sensitivity analyses using different outcome definitions or model adjustments, reinforcing the robustness of the study findings. Subgroup analysis identified an excess of ICH frequency in patients without diagnosed hypertension (adjusted hazard ratio 1.36 [1.11-1.67]). CONCLUSIONS: In general, no association was observed between cumulative statin use and the risk of ICH among subjects without a previous history of stroke. An increased risk was identified among the nonhypertensive cohort, but this finding should be interpreted with caution.
BACKGROUND: Reports of statin usage and increased risk of intracranial hemorrhage (ICH) have been inconsistent. This study examined potential associations between statin usage and the risk of ICH in subjects without a previous history of stroke. METHODS AND RESULTS:Patients initiating statin therapy between 2005 and 2009 without a previous history of ischemic or hemorrhagic stroke were identified from Taiwan's National Health Insurance database. Participants were stratified by advanced age (≥70 years), sex, and diagnosed hypertension. The outcome of interest was hospital admission for ICH (International Classification of Diseases, Ninth Revision, Clinical Modification codes 430, 431, 432). Cox regression models were applied to estimate the hazard ratio of ICH. The cumulative statin dosage stratified by quartile and adjusted for baseline disease risk score served as the primary variable using the lowest quartile of cumulative dosage as a reference. There were 1 096 547 statin initiators with an average follow-up of 3.3 years. The adjusted hazard ratio for ICH between the highest and the lowest quartile was nonsignificant at 1.06 with a 95% confidence interval spanning 1.00 (0.94-1.19). Similar nonsignificant results were found in sensitivity analyses using different outcome definitions or model adjustments, reinforcing the robustness of the study findings. Subgroup analysis identified an excess of ICH frequency in patients without diagnosed hypertension (adjusted hazard ratio 1.36 [1.11-1.67]). CONCLUSIONS: In general, no association was observed between cumulative statin use and the risk of ICH among subjects without a previous history of stroke. An increased risk was identified among the nonhypertensive cohort, but this finding should be interpreted with caution.
Authors: Jan F Scheitz; Rachael L MacIsaac; Azmil H Abdul-Rahim; Bob Siegerink; Philip M Bath; Matthias Endres; Kennedy R Lees; Christian H Nolte Journal: Neurology Date: 2016-03-25 Impact factor: 9.910