What type of lipid-lowering agent is recommended for secondary prevention of stroke?

From the Guidelines

Statins are the preferred lipid-lowering agents for secondary prevention of stroke, with a goal to achieve a target LDL cholesterol consistently less than 2.0 mmol/L or >50% reduction of LDL cholesterol, from baseline. According to the most recent guideline from the American Heart Association/American Stroke Association 1, high-intensity statins such as atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily are recommended for patients who have experienced a stroke or transient ischemic attack (TIA), particularly those with atherosclerotic disease. The Canadian Stroke Best Practice Recommendations also support the use of statins for secondary prevention of stroke, with a target LDL cholesterol of less than 2.0 mmol/L or a >50% reduction from baseline 1.

Key Considerations

• For patients who cannot tolerate high-intensity statins, moderate-intensity options include atorvastatin 10-20 mg, rosuvastatin 5-10 mg, simvastatin 20-40 mg, or pravastatin 40-80 mg daily.
• Treatment should be initiated as soon as possible after the stroke event and continued indefinitely.
• The goal is to reduce LDL cholesterol by at least 50% from baseline or to achieve levels below 70 mg/dL.
• Statins work by inhibiting HMG-CoA reductase, reducing cholesterol synthesis in the liver and increasing LDL receptor expression, which enhances clearance of LDL from the bloodstream.
• Beyond lipid-lowering effects, statins provide additional benefits through anti-inflammatory, antithrombotic, and endothelial function-improving properties, which contribute to their effectiveness in preventing recurrent strokes.

Alternative Options

• For patients with complete statin intolerance, alternatives include ezetimibe 10 mg daily or PCSK9 inhibitors (evolocumab 140 mg every 2 weeks or alirocumab 75-150 mg every 2 weeks), though these should be considered second-line options.
• The choice of alternative therapy should be individualized based on patient-specific factors, such as comorbidities and concomitant medications.

Clinical Implications

• The use of statins for secondary prevention of stroke has been consistently shown to reduce the risk of recurrent stroke and other major cardiovascular events 1.
• Clinicians should prioritize the use of high-intensity statins and aim to achieve the recommended target LDL cholesterol levels to maximize the benefits of therapy.

From the FDA Drug Label

Atorvastatin calcium significantly reduced the risk of stroke by 48% (21 events in the atorvastatin calcium group vs. 39 events in the placebo group), HR 0.52,95% CI (0.31,0.89) (p=0. 016) The primary endpoint was the occurrence of any of the major cardiovascular events: myocardial infarction, acute CHD death, unstable angina, coronary revascularization, or stroke.

Statins, such as atorvastatin, are a type of lipid-lowering agent that can be used in the secondary prevention of stroke.

• The use of atorvastatin has been shown to significantly reduce the risk of stroke by 48% in patients with type 2 diabetes 2.
• The reduction in stroke risk was observed regardless of age, sex, or baseline lipid levels.
• Atorvastatin can be considered a suitable option for secondary prevention of stroke in patients with a history of cardiovascular disease or at high risk of cardiovascular events.

From the Research

Lipid Lowering Agents for Secondary Prevention of Stroke

• Statins are recommended for secondary prevention of stroke to reduce the risk of new stroke or major cardiovascular events 3, 4, 5, 6.
• Intensive statin therapy, which lowers LDL-cholesterol beyond 1.8 mmol/L (70 mg/dl), seems to be more effective than less intensive treatment without increasing the risk of side effects 3.
• The combination of atorvastatin 40 mg plus ezetimibe 10 mg may be more effective in reducing LDL-cholesterol levels than atorvastatin 80 mg alone 7.
• Statin-based lipid-lowering therapy is associated with a lower risk of ischemic stroke in both primary and secondary prevention settings 5.
• The use of statins, ezetimibe, or proprotein convertase subtilisin/kexin type 9 inhibitors may be considered for cholesterol-lowering therapy in secondary stroke prevention 6.

Considerations for Treatment

• The treatment should be individualized based on the patient's risk factors, such as carotid artery stenosis, and the presence of other cardiovascular diseases 3, 4.
• The risk of cerebral hemorrhage should be considered when initiating statin therapy, especially in patients with a history of hemorrhagic stroke 3, 4.
• The treatment goals should include achieving low levels of LDL-cholesterol, with a target of less than 1.8 mmol/L (70 mg/dl) 3, 5.