What is the role of HMG-CoA reductase inhibitors (statins) in the management of stroke?

From the Guidelines

Statins are strongly recommended for patients who have experienced a stroke or are at risk for stroke, with high-intensity statins like atorvastatin 80 mg daily being initiated promptly after an ischemic stroke or transient ischemic attack (TIA) to reduce stroke recurrence and major cardiovascular events. The 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack, published in the journal Stroke 1, supports the use of statins in secondary prevention, with a target LDL-C < 70 mg/dL. The SPARCL trial, also cited in the guideline, found that atorvastatin 80 mg daily reduced stroke recurrence in patients without another indication for statin therapy.

Key Points

• Statins should be continued indefinitely for secondary prevention of stroke, with a focus on high-intensity statins for patients with a history of ischemic stroke or TIA.
• The goal of statin therapy is to achieve a target LDL-C < 70 mg/dL or a reduction of at least 50% from baseline, as recommended by the 2021 guideline 1.
• Statins work by reducing LDL cholesterol levels, stabilizing atherosclerotic plaques, decreasing inflammation, and improving endothelial function, which helps prevent both first-time and recurrent strokes.
• Beyond cholesterol reduction, statins provide neuroprotective effects that may limit brain injury during acute stroke, as suggested by the Canadian Stroke Best Practice Recommendations 1.

Considerations

• Regular monitoring of lipid levels and liver function is recommended, with attention to potential side effects such as muscle pain, liver enzyme elevations, and slightly increased risk of diabetes.
• The choice of statin and dosage should be individualized based on patient characteristics, such as history of coronary heart disease, diabetes, and other risk factors, as outlined in the 2018 Canadian Stroke Best Practice Recommendations 1.
• Statin therapy is not indicated for prevention of intracerebral hemorrhage, as noted in the 2018 Canadian Stroke Best Practice Recommendations 1.

Evidence Summary

The evidence from recent studies, including the 2021 guideline 1 and the SPARCL trial, supports the use of high-intensity statins in secondary prevention of stroke, with a focus on reducing LDL-C levels and preventing major cardiovascular events. The 2018 Canadian Stroke Best Practice Recommendations 1 also emphasize the importance of statin therapy in secondary prevention, with a target LDL-C < 2.0 mmol/L or >50% reduction from baseline. Overall, the evidence suggests that statins play a critical role in the management of stroke, and their use should be guided by current guidelines and individual patient characteristics.

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. To reduce the risk of major adverse cardiovascular (CV) events (CV death, nonfatal myocardial infarction, nonfatal stroke, or an arterial revascularization procedure) in adults without established coronary heart disease who are at increased risk of CV disease

The role of HMG-CoA reductase inhibitors (statins) in the management of stroke is to reduce the risk of stroke in adults with multiple risk factors for coronary heart disease (CHD) or with type 2 diabetes mellitus, as well as in adults without established CHD who are at increased risk of CV disease 23. Key benefits of statins in stroke management include:

• Reducing the risk of nonfatal stroke
• Reducing the risk of major adverse cardiovascular events, including nonfatal stroke
• Slowing the progression of atherosclerosis, which can help reduce the risk of stroke

From the Research

Role of HMG-CoA Reductase Inhibitors (Statins) in Stroke Management

• Statins are widely recommended for the primary and secondary prevention of ischemic stroke in patients with increased cardiovascular risk 4, 5, 6.
• The use of statins has been shown to reduce the risk of major vascular events, including ischemic stroke, by 21.1% for each 1 mmol/L decrease in low-density lipoprotein cholesterol 5.
• Statins are effective in decreasing the risk of further strokes, with a significant benefit observed in men and women, aged patients, and possibly to a greater extent in patients with carotid artery stenosis 7.
• Intensive statin therapy, lowering LDL-cholesterol beyond 1.8 mmol/L, seems to be more effective than less intensive treatment without an increased risk of side effects 7.

Benefits and Risks of Statin Therapy in Stroke Prevention

• Statins have been shown to reduce the risk of recurrent stroke by 12-16% in patients with ischemic stroke or transient ischemic attacks (TIA) presumed to be of atherosclerotic origin or with other comorbid atherosclerotic cardiovascular disease 5, 6.
• The use of statins is not associated with an increased risk of intracranial bleeding in primary prevention studies, but may be associated with an increased incidence of non-fatal hemorrhagic stroke with high-dose statins in patients with a previous cerebrovascular event 6.
• A systematic review and meta-analysis found that statins reduce the risk of recurrent stroke of any type, mediated through a reduction of ischemic stroke, without a significant increase in the risk of hemorrhagic stroke 8.

Clinical Implications

• Statins are recommended for patients with established coronary heart disease, those with a previous cerebrovascular event, and those at high risk of stroke 4, 5, 6.
• Patients who experience a stroke while on statins should not discontinue statins, and statins may be associated with better survival and improved functional outcome when administered during the acute phase of stroke in statin-naive patients 6.