There is a knowledge gap and clinical equipoise as to whether statins should be used in patients at high risk for intracerebral hemorrhage (ICH), in particular patients with lobar ICH who are at high risk for recurrent ICH. While the benefits of statins in reducing major adverse cerebro-cardio-vascular events (MACCE) are well established, statins have been linked to a slight increase in the incidence of ICH, particularly in lobar ICH patients who have Apolipoprotein E ?2 and/or ?4 genotypes, and the presence/number of microbleeds on gradient-echo MRI. There are no prospective or randomized data on the effects of continuation vs. discontinuation of statins after ICH regarding the risks of ICH recurrence and incidence of MACCE, or long- term functional or cognitive outcomes, or quality of life. We propose a multi-center, pragmatic, prospective, randomized, open-label, Phase III clinical trial with blinded end-point assessment (PROBE) in patients with lobar ICH taking statins to determine whether continuation or discontinuation of these drugs is the best strategy. We specifically wish to evaluate the effects of discontinuing vs. continuing statins on the risk of recurrent symptomatic ICH, and the occurrence of MACCE (symptomatic ischemic stroke, symptomatic myocardial infarction, newly symptomatic arterial occlusive disease (peripheral, retinal, or carotid), revascularization procedures for coronary, carotid, or peripheral arterial disease, and vascular death) during 24 months of follow-up in patients presenting with lobar ICH while taking a statin. We will also examine: 1) quality of life, functional, and cognitive outcomes in patients in whom statins are continued vs. discontinued, by repeated assessments of the EQ-5D quality of life questionnaire, modified Rankin Scale, and Telephone Montreal Cognitive Assessment at 3, 6, 9, 12, 18, and 24 months; and 2) whether the presence vs. absence of APOE ?2 and/or ?4 genotypes modifies the effects of statins on the risk of recurrent ICH, (i.e. whether APOE genotype can be used as a biological marker to stratify the risk of ICH recurrence in statins-treated patients). We hypothesize that: 1) discontinuation of statins in patients with lobar ICH is likely associated with reduced risk of ICH recurrence; and 2) patients with lobar ICH and APOE ?2 and/or ?4 genotypes have an increased risk of recurrent ICH with continuation of statins therapy; and that avoiding statins in this subset of patients with these biological markers might be helpful to reduce the risk of ICH recurrence. This proposed study within the NIH StrokeNet will answer an important clinical question relevant to everyday practice. This study will also provide a unique opportunity to simultaneously address important areas in ICH research identified by the NINDS PRG and StrokeNet: 1) prevention of ICH recurrence; and 2) biomarkers that may modify treatment decisions in stroke patients. Successful studies aiming to prevent ICH and its recurrence would have significant public health and cost-saving implications.
Approximately 70,000 Americans suffer from a brain hemorrhage each year. Although brain hemorrhage is a major cause of death and permanent disability, a substantial number of patients may be able to function independently afterwards and would benefit from avoiding a recurrent and disabling hemorrhage. This project aims to investigate possible ways to decrease the recurrence of brain hemorrhage in patients who survive their first hemorrhage. It can have important clinical implications to improve the welfare of these patients and their families; and to minimize healthcare-related expenses.
