Kevin S. Attenhofer, MD
Statins are some of the most commonly prescribed drugs in the fields of cardio- and cerebrovascular disease. In the last two decades, randomized controlled trials have shown that statin therapy reduces the risk of major vascular events in high-risk populations. Definitions of these populations have changed over the years, but currently the AHA/ASA stroke guidelines recommend statins in all patients for secondary stroke prevention.
Despite the ubiquitous usage of statins, it has been noted that some data (from the Heart Protection Study (HPS) and the Stroke Prevention with Aggressive Reductions of Cholesterol Levels (SPARCL)) suggests that the benefits of high-dose atorvastatin treatment was partially offset by an increase in hemorrhagic stroke. The association of statins and intracerebral hemorrhage (ICH) has remained controversial ever since. Subsequent meta-analyses and case control studies — some of which included data from SPARCL — found no associated increase in the risk of ICH in patients on statin therapy.
In this paper, Gaist et al. used data from The Health Improvement Network (THIN) in the UK to further study the relationship between statin therapy and risk of ICH in patients with prior stroke or TIA. They followed diagnosis codes and electronic prescription records of deidentified patients in a prospective registry over 14 years. They classified patients as either non-use of statin, current use of statin (last dose 0–7 days prior to ICH), or past use of statin (last dose 8–365 days prior to ICH).
A total of 157 ICH cases and 884 controls were identified. Controls were randomly sampled within the 2 study cohorts and frequency matched to intracranial hemorrhage cases by age, sex, and calendar year. As described below in Table 2 from the paper, current statin use was not associated with increased risk of ICH; however, the risk of ICH was higher among past statin users. They do not have a concrete explanation for this finding, but hypothesize that statin withdrawal might lead to changes in pleiotropic vascular effects, which, in turn, increases the propensity of vascular disruption and hemorrhage.
The authors conclude that current statin use is not associated with an increased risk of intracranial hemorrhage. These results are consistent with previous meta-analyses, as mentioned above. They suggest that the increased risk of ICH associated with statin use that was found in exploratory analyses of HPS and SPARCL may have been because of chance. This paper adds more evidence to the growing volume of literature that supports statin usage and argues that statins should not be withheld in patients with an ischemic stroke or TIA because of concern for ICH.