What are the indications to start statin (HMG-CoA reductase inhibitor) therapy after an ischemic stroke?

From the Guidelines

Statin therapy should be initiated for all patients who have experienced an ischemic stroke with no known coronary heart disease, no major cardiac sources of embolism, and LDL cholesterol (LDL-C) >100 mg/dL, with atorvastatin 80 mg daily indicated to reduce the risk of stroke recurrence. This recommendation is based on the 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack from the American Heart Association/American Stroke Association 1. The guideline suggests that in patients with ischemic stroke or TIA and atherosclerotic disease, lipid-lowering therapy with a statin and also ezetimibe, if needed, to a goal LDL-C of <70 mg/dL is recommended to reduce the risk of major cardiovascular events.

Key points to consider:

• High-intensity statins such as atorvastatin 80 mg daily are recommended as first-line therapy for patients with ischemic stroke and LDL-C >100 mg/dL.
• The target LDL-C level is generally below 70 mg/dL (1.8 mmol/L) for secondary prevention.
• Statins provide pleiotropic effects including plaque stabilization, reduced inflammation, improved endothelial function, and decreased thrombogenicity, all of which contribute to stroke prevention.
• Regular monitoring of liver function tests and creatine kinase is recommended, especially during the first year of therapy, to detect potential side effects.

The 2021 guideline 1 and other studies 1 support the use of statin therapy in patients with ischemic stroke, with a focus on reducing the risk of stroke recurrence and major cardiovascular events. The SPARCL trial, referenced in the guideline, found that atorvastatin 80 mg daily reduced stroke recurrence in patients without another indication for statin therapy 1. Overall, the evidence suggests that statin therapy should be initiated as soon as possible after an ischemic stroke, ideally within 24-48 hours, and continued indefinitely.

From the FDA Drug Label

To reduce the risk of: Myocardial infarction (MI), stroke, revascularization procedures, and angina in adults with multiple risk factors for coronary heart disease (CHD) but without clinically evident CHD MI and stroke in adults with type 2 diabetes mellitus with multiple risk factors for CHD but without clinically evident CHD. Non-fatal MI, fatal and non-fatal stroke, revascularization procedures, hospitalization for congestive heart failure, and angina in adults with clinically evident CHD.

The indication to start statin therapy after ischemic stroke is to reduce the risk of non-fatal and fatal stroke in adults with clinically evident coronary heart disease, as well as to reduce the risk of myocardial infarction, stroke, revascularization procedures, and angina in adults with multiple risk factors for coronary heart disease but without clinically evident CHD 2. Key points:

• Statin therapy is indicated to reduce the risk of major adverse cardiovascular events, including stroke, in adults with increased risk of CV disease.
• The decision to start statin therapy after ischemic stroke should be based on the individual patient's risk factors and clinical profile.
• It is essential to assess the patient's LDL-C levels and other cardiovascular risk factors before initiating statin therapy 2.

From the Research

Indication to Start Statin Therapy After Ischemic Stroke

• The decision to start statin therapy after an ischemic stroke is supported by several studies that demonstrate the effectiveness of statins in reducing the risk of recurrent stroke and major cardiovascular events 3, 4, 5, 6, 7.
• A study published in The New England Journal of Medicine in 2006 found that high-dose atorvastatin reduced the risk of recurrent stroke by 2.2% over 5 years in patients with a recent stroke or transient ischemic attack 3.
• Another study published in Annals of Neurology in 2024 found that post-stroke statin therapy was associated with a lower risk of major vascular events during 1-year follow-up, even in patients with low baseline low-density lipoprotein cholesterol levels 4.
• A systematic review and meta-analysis of randomized controlled trials and observational cohort studies published in Neuroepidemiology in 2022 found that statins reduced the odds of recurrent stroke of any type in patients with an initial ischemic stroke 5.
• A prospective cohort study published in Journal of Clinical Neuroscience in 2020 found that simvastatin 40 mg was associated with a significantly lower incidence of stroke recurrence and better functional recovery in patients with cardioembolic stroke 6.
• A study published in Neurology in 2006 found that approximately one out of three guideline-eligible high vascular risk ischemic stroke patients had low-density lipoprotein cholesterol concentrations above qualifying levels for pharmacologic therapy, but half of these patients were not taking a statin, and of those receiving statin treatment, less than half were within recommended lipid goals 7.

Key Findings

• Statins reduce the risk of recurrent stroke and major cardiovascular events in patients with ischemic stroke 3, 4, 5, 6.
• The benefit of statin therapy is observed even in patients with low baseline low-density lipoprotein cholesterol levels 4.
• High-dose atorvastatin is effective in reducing the risk of recurrent stroke in patients with a recent stroke or transient ischemic attack 3.
• Simvastatin 40 mg is associated with a significantly lower incidence of stroke recurrence and better functional recovery in patients with cardioembolic stroke 6.
• There is a need to improve the implementation of national cholesterol guidelines and increase the use of statin therapy in eligible patients with ischemic stroke 7.