Statins and Risk of Intracerebral Haemorrhage in a Stroke-Free Population: A Nationwide Danish Propensity Score Matched Cohort Study

Abstract

Background: Statins may increase the risk of intracerebral haemorrhage (ICH) in individuals with previous stroke. It remains unclear whether this applies to individuals with no history of stroke. This study is the first to explore the statin-associated risk of ICH in stroke-free individuals while considering the timing of statin initiation. Methods: We conducted a population-based, propensity score matched cohort study using information from five Danish national registers. We included all stroke-free individuals initiating statins in 2004–2013 and a propensity score matched group of non-users. Adjusted hazard ratios (aHRs) for ICH risk among statin users compared to non-users were calculated as a function of time since statin initiation. Findings: 519,894 stroke-free individuals initiating statins and their 1:5 matched stroke-free reference subjects were included and followed for up to ten years. During this period, 1409 ICHs occurred in statin users. Statin users had an overall aHR of 0.85 (95% confidence interval: 0.80–0.90) compared to non-users, but this risk was modified by time since statin initiation. Statin users and non-users had similar ICH risk during the first six months after statin initiation. Hereafter, statin users had a 22–35% lower risk throughout the study period. Interpretation: Statin users had lower ICH risk than non-users from six months after statin initiation. This finding could not be explained by healthy initiator bias or differences between users and non-users in terms of sociodemographic characteristics, comorbidity, or parallel treatment regimens. Our study suggests that statin use in stroke-free populations is associated with reduced ICH risk. Funding: The Novo Nordisk Foundation. Keywords: Intracerebral haemorrhage, Ischaemic stroke, Statins, Epidemiology