Statins May Increase Intracerebral Hemorrhage Volume

Abstract

Several epidemiological studies have demonstrated an association between hypocholesterolemia and the incidence of intracerebral hemorrhage (ICH).1-3 HMG-CoA reductase inhibitors (statin) may theoretically increase the risk of cerebral hemorrhage, given its cholesterol-lowering effect. In addition, statins have been associated with decreased platelet function via direct influence on platelet membrane and inhibition of PAR-1, which is a cell-bound protein that links platelet activation. [4][5][6] An exploratory analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial found that statins overall effect included an increase in the number of treated patients having hemorrhagic stroke (n 55 for active treatment vs n 33 for placebo) with an unadjusted HR 1.68. 7 The Heart Protection Study (HPS) earlier described this ABSTRACT: Background: Some studies have suggested an association between hypocholesterolemia and intracerebral hemorrhage (ICH). In the SPARCL trial, statin use increased ICH risk. We tested the hypothesis that use of statins affects the volume of spontaneous ICH and contributes to the progression of ICH volume between baseline and follow-up CT scans. Methods: Consecutive cases of spontaneous ICH were reviewed. Secondary causes were excluded. We measured ICH volume on the baseline and follow-up CT scans using the AxBxC/2 method. Multivariate analysis and logistic regression modeling were used. The primary outcome was the ICH volume on the baseline CT scan. Secondary outcomes included volume variation between the baseline and the first follow up CT scans and death. Results: Of 303 subjects, 71 were taking a statin at the time of the ICH (23%). Statin users were significantly more likely to be younger, to have co-morbidities and take anticoagulant or anti-platelet medication. They also had a higher baseline ICH volume than non-statin users (median 31.

Statins in Intracerebral Hemorrhage

“…Similarly, in previous investigations, very low levels of LDL have been described to be associated with cortical or lobar MBs [38]. In addition, admission hematoma volumes were increased in statintreated patients with lobar ICH, while this relationship was not found in patients with deep ICH [39]. All of these observational data suggest a link between statins and risk of CAArelated lobar ICH.…”

“…Although the underlying pathology differs from spontaneous ICH, a dose-dependent effect may exist. Yet, an impact on mortality or worsened functional outcome could not be detected in these and other studies [43,44,39,28]. Another study in a cohort of 399 patients found even smaller baseline hematoma volumes in prior statin users [45].…”

“…A large randomized trial, in which treatment with rosuvastatin reduced the incidence of symptomatic venous thromboembolism in apparently healthy individuals over a median 1.9-year follow-up, suggests that these proposed hypocoagulable effects can have clinical consequences [43]. In a retrospective study, statin use was associated with increased baseline hematoma volumes and hematoma growth [39]. In patients suffering ischemic stroke, a statin dose-dependent increase in cerebral hemorrhage risk has been observed after intravenous thrombolysis [44].…”

Potential role of statins in the intracerebral hemorrhage and subarachnoid hemorrhage

“…No association between functional outcome; decreased mortality Naval et al [37] 125 Preadmission statin use with volume of perihematomal edema on initial head CT Reduced volume of perihematomal edema Ricard et al [38] 303 Preadmission statin use with ICH volume variation of first follow up CT scans and death…”

Warfarin and Statins are Associated with Hematoma Volume in Primary Infratentorial Intracerebral Hemorrhage

“…The association between hematoma volume and clinical outcome is equally strong in both supra- and infratentorial ICH [2]. For supratentorial hemorrhages, several factors have been reported to influence hematoma volume, including treatment with warfarin [3] and statins [4], leukoaraiosis [5], asymptomatic microbleeds [6], and the APOE epsilon-2 allele [7]. …”