Mark R. Etherton, MD, PhD
In this entry, I discuss a recent publication by Fazeel Siddiqui and colleagues regarding the use of statins and outcomes after intracerebral hemorrhage (ICH).
The current evidence suggests a complex relationship between serum cholesterol levels, statin use, and outcomes after ICH. Low serum cholesterol levels have been associated with increased incidence of ICH, as well as hematoma expansion. However, a prior meta-analysis demonstrated antecedent statin use was associated with decreased risk of mortality and increased likelihood of a good outcome after ICH (Jung et al. Int J Stroke. 2015). The authors, therefore, set out to investigate the relationship of statin use with ICH outcomes by evaluating 3-month disability, mortality, and hematoma size/expansion.
Using data from the ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) study, the authors enrolled 2,457 patients. Of the 1,093 statin users, 25% were prior users, 37% were newly prescribed, and 39% were continued on statins after their admission. The primary outcome was the effect of statin use on 3-month mortality and modified Rankin scale (mRS) after ICH. Hematoma expansion was assessed as the secondary outcome.
When the population was dichotomized into statin users versus nonusers, there were significant differences in the baseline demographics. Statin users were older (65.1 vs. 60.3 years) and more likely to have history of prior ischemic stroke, diabetes, hypertension, and hyperlipidemia. At 3 months, there was a significantly higher risk of death (26% vs. 17.5%) in the nonstatin group. No association between hematoma size and expansion was observed between the two groups.
An important consideration for the interpretation of these results, which the authors explore, is the difference in demographics between the different statin groups, as well as the nonstatin group. Namely, the prior statin group was older and had more risk factors, increased incidence of lobar hemorrhage (43.3% vs. 29.8%), and decreased pre-stroke mRS=0 (52.5% vs. 74.4%) compared to the nonstatin group. On multivariate analysis, the prior statin group had higher mortality and 3-month mRS than either the continued or new statin groups.
The authors set out to address this apparent discordant observation whereby the prior statin group had worse outcomes and the collective statin group had better outcomes after ICH than the nonstatin counterparts. Their main hypothesis was that the prior statin group represented an extremely sick population that carried a poor long-term prognosis, which resulted in their statin medication being discontinued. The baseline demographics of the prior statin group reflect this hypothesis. As mentioned earlier, the prior statin group was older, had more antecedent co-morbidities, had larger hematoma volume, were more likely to have IVH, and had worse premorbid mRS. Using a propensity score to incorporate variables that would influence a physician’s decision to stop statin therapy, the previously observed effect of the prior statin group having higher mortality was reduced and no longer statistically significant.
The interpretation of these results is complex. In this population, statin use was associated with decreased 3-month mortality compared to the nonstatin group. This effect, however, was heavily weighted by those patients that were continued on their statin or had statin therapy initiated as a result of their ICH. Patients that had statin therapy discontinued after hospitalization for ICH had worse outcomes than the nonstatin group, a finding likely explained by differences in ICH severity and worse prognosis in this group.
While the differences in demographics of the groups complicate the interpretation of this study, there are several important points presented in this article. First, statin therapy was not associated with hematoma expansion. Secondly, continuing or initiating therapy while hospitalized for ICH was not associated with worse 3-month outcomes. Lastly, this article underscores the need for a randomized controlled trial looking at statin therapy in statin-naïve ICH patients.