Rajbeer Singh Sangha, MD

Priglinger M, Arima H, Anderson C, and Krause M. No Relationship of Lipid-Lowering Agents to Hematoma Growth: Pooled Analysisof the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials Studies. Stroke. 2015

Controversy persists over whether statins increase the risk of intracerebral hemorrhage (ICH). A recent systematic overview of randomized trials found no association of statins and the risk of ICH, but less evidence exists for populations with high rates of ICH. Statins do not appear to increase risks of poor functional outcomes in ICH, but no study has examined their association with hematoma growth which may be promoted by ancillary mechanisms. Previous studies have was shown that statins increase fibrinolytic and/or decrease pro-thrombotic mechanisms in vitro. In aortic endothelial cells, statins increase mRNA and enzymatic activity of tissue type plasminogen activator (tPA) (Essig et al., 1998), and decrease mRNA and activity of plasminogen activator inhibitor-type1 (PAI-1) (Bourcier and Libby, 2000). These mechanisms suggest that statins may lead to inhibition of platelet aggregation and thrombogenesis and thereby postulated to affect hematoma growth. The authors of this study examined associations of lipid lowering therapy, hematoma growth and clinical outcomes in participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT).

The authors analyzed the data from the INTERACT trials (1 and 2) which were international, multicenter, open, blinded endpoint, randomized controlled trials with a common protocol that collectively compromised 3243 patients with spontaneous ICH (<6 hours of onset) and elevated systolic blood pressure (SBP 150-220mmHg) randomly allocated to receive intensive or guideline-based BP management. Out of 3184 participants included in the analyses, 204 (6.5%) were on lipid lowering therapy at the time of ICH. 90 day clinical outcomes were not significantly different after adjustment for confounding variables including region and age. In the CT substudy, analysis of 24 hour hematoma growth was greater in 124 patients (9%) with, compared to those without, prior lipid lowering therapy. However, this association was not significant between the two groups (9.2ml vs 6.8ml, p<0.13), after adjustment for prior antithrombotic therapy. This study found no difference in clinical outcomes, initial ICH volume, or 24 hour hematoma volume growth between patients with and without lipid lowering therapy at the time of acute ICH.

After multiple studies, analyses and debates, the evidence seems to be pointing towards the safe utilization of statins during acute ICH. While many of these studies are underpowered to determine a significant effect of statins, the safety profile continues to be established in favor of statin use. It seems that until no large multicenter center does not analyze the effect statins have on ICH we won’t have a conclusive answer and the “controversy” will continue to rage on. Of course, there is the very real possibility that statin use will be limited in the next five years as lipid lowering agents will most likely be comprised of a new class of drugs.

1. Bourcier T, Libby P. HMG-CoA reductase inhibitors reduces plasminogen activator inhibitor-1 expression by human vascular smooth muscle and endothelial cells. Arterioscler Thromb Vasc Biol 2000;20:556–562
2. Essig M, Nguyen G, Prie D, Escoubet B, Sraer J-D, Friedlander G. 3-hydroxy-3-methylglutarylCoenzyme A reductase inhiitors increase fibrinolytic activity in rat aortic endothelial cells. Circ Res 1998;83:683–690.