The Impact of Antiplatelet Use on the Risk of Intracerebral Hemorrhage in Patients with Alzheimer’s Disease: A Nationwide Cohort Study¹

Article type: Research Article

Authors: Lee, Tsung-Lin^{a; 2} | Liu, Chi-Hung^{b; 2} | Chang, Yu-Ming^{a; 2} | Lin, Tien-Yu^{a; 2} | Chien, Chung-Yao^{a; 2} | Chen, Chih-Hung^{a; 2} | Tsai, Kuen-Jer^{c; 2} | Lin, Sheng-Hsiang^{c; d; e; 2; 3} | Sung, Pi-Shan^{a; c; 2; 3; *}

Affiliations: [a] Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan | [b] Stroke Center and Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center and College of Medicine, Chang Gung University, Taoyuan, Taiwan | [c] Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan | [d] Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan | [e] Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Correspondence: [*] Correspondence to: Pi-Shan Sung, MD, No. 138, Sheng Li Road, Tainan, Taiwan 704, R.O.C. Tel.: +886 6 2353535 5481; Fax: +886 6 2374285; E-mail: pishansung@gmail.com.

Note: [1] This article received a correction notice (Erratum) with the reference: 10.3233/JAD-209008, available at https://content.iospress.com/articles/journal-of-alzheimers-disease/jad209008.

Note: [2] These authors contributed equally to this work.

Note: [3] The statistical analyses were conducted by Sheng-Hsiang Lin, PhD and Pi-Shan Sung, MD.

Abstract: Background:Antiplatelet use on the risk of intracerebral hemorrhage (ICH) in patients with Alzheimer’s disease (AD) has not yet been completely elucidated. Objective:This large epidemiologic study aims to estimate the risk of ICH in AD patients treated with antiplatelet therapy (APT). Methods:Using data from Taiwan’s National Health Insurance Research Database, ICH risk in APT-treated AD patients with a validated diagnosis (N = 824) was determined. AD without APT and non-AD with and without APT comparison cohorts were selected. To adjust for confounders and competing risk of death, inverse probability of treatment weighting using propensity scores and competing risks regression (CRR) were applied. Cox proportional hazards regression analysis estimated ICH risk in all cohorts comparing with non-AD without APT. Results:Among the 824 AD patients with APT, 79.6% were prescribed aspirin. ICH incidence rates in the AD (with/without APT) and non-AD (with/without APT) cohorts were 2.88/2.70 and 2.24/1.20 per 1,000 person-years, respectively. Overall, AD with (adjusted hazards ratio (aHR), 2.29; 95% CI, 1.19–4.38) and without (aHR, 1.97; 95% CI, 1.08–3.61) APT and non-AD with APT (aHR, 1.80; 95% CI, 1.34–2.42) were at a higher risk and had elevated subdistribution HR obtained from CRR than non-AD without APT controls. However, the risk was comparable between the AD cohorts with and without APT (HR, 1.16; 95% CI, 0.51–2.66). Conclusions:Our study indicated both the APT and non-APT users in AD population yielded higher ICH risks. However, whether APT use potentiate the risk of ICH in AD patients may warrant further evaluation.

Keywords: Alzheimer’s disease, antiplatelet therapy, aspirin, intracranial hemorrhage, risk

DOI: 10.3233/JAD-190762

Journal: Journal of Alzheimer's Disease, vol. 73, no. 1, pp. 297-306, 2020