What are the statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor) recommendations for patients after a cerebrovascular accident (CVA) or stroke?

From the Guidelines

Statin therapy is strongly recommended for most patients after a stroke or transient ischemic attack (TIA) to prevent recurrent events, with high-intensity statins like atorvastatin 80mg daily being the preferred choice for secondary prevention, as evidenced by the SPARCL trial 1 and the 2021 guideline for the prevention of stroke 1. The goal of statin therapy in patients with atherosclerotic stroke is to reduce LDL cholesterol by at least 50% from baseline or to below 70 mg/dL, as recommended by the 2023 systematic review and synthesis of global stroke guidelines 1. Some key points to consider when prescribing statins for patients after a stroke or TIA include:

• Starting treatment as soon as possible after the stroke, ideally within 24-48 hours, and continuing indefinitely
• Monitoring liver function tests and creatine kinase regularly, especially in the first few months of therapy
• Considering moderate-intensity statins (such as atorvastatin 10-20mg, rosuvastatin 5-10mg, simvastatin 20-40mg, or pravastatin 40-80mg daily) for patients who cannot tolerate high-intensity therapy
• Adding ezetimibe to atorvastatin to reach the target LDL-cholesterol level of < 1.8 mmol/L (70 mg/dL) in patients with ischemic stroke and TIA and atherosclerotic disease of the extracranial or intracranial arteries, as recommended by the 2023 systematic review and synthesis of global stroke guidelines 1
• Referring patients to an expert in lipid management for consideration of adding a PCSK9 inhibitor if the target LDL-cholesterol level is not achievable, as recommended by the 2023 systematic review and synthesis of global stroke guidelines 1. The use of statins in patients after a stroke or TIA has been shown to have additional pleiotropic effects, including anti-inflammatory, antithrombotic, and endothelial function improvement, which contribute to stroke prevention beyond cholesterol reduction, as discussed in the 2021 guideline for the prevention of stroke 1.

From the FDA Drug Label

In SPARCL, 4,731 patients (age range 21 to 92 years, 40% female; 93% White, 3% Black or African American, 1% Asian, 3% other) without clinically evident CHD but with a stroke or transient ischemic attack (TIA) within the previous 6 months were treated with atorvastatin calcium 80 mg (n=2,365) or placebo (n=2,366) for a median follow-up of 4.9 years. In a post-hoc analysis, atorvastatin calcium 80 mg reduced the incidence of ischemic stroke (9.2% vs. 11.6%) and increased the incidence of hemorrhagic stroke (2.3% vs. 1. 4%) compared to placebo.

The statin recommendations for patients after a cerebrovascular accident (CVA) or stroke are to consider treatment with atorvastatin calcium 80 mg, as it reduced the incidence of ischemic stroke in the SPARCL trial 2. However, it also increased the incidence of hemorrhagic stroke, and patients who entered the trial with a hemorrhagic stroke appeared to be at increased risk for hemorrhagic stroke. Key points to consider are:

• Ischemic stroke reduction: atorvastatin calcium 80 mg reduced the incidence of ischemic stroke.
• Hemorrhagic stroke risk: atorvastatin calcium 80 mg increased the incidence of hemorrhagic stroke.
• Patient selection: consider the individual patient's risk factors and history before initiating treatment.

From the Research

Statin Recommendations After a Stroke

• The 2013 ACC/AHA cholesterol guideline recommends using high-intensity statin therapy to reduce atherosclerotic cardiovascular disease (ASCVD) risk in patients who have had a stroke or other clinical ASCVD event, up to age 75 years, unless there are safety concerns 3.
• A moderate-intensity statin is recommended if there are safety concerns or age is greater than 75 years 3.
• High-intensity statins, such as atorvastatin 40-80 mg and rosuvastatin 20-40 mg, are considered effective in reducing ASCVD risk 3.
• Statin therapy has been shown to reduce the risk of stroke in patients with coronary artery disease (CAD) and in patients without CAD but at high cardiovascular risk, or with diabetes mellitus 4.

Effectiveness of High-Intensity Statin Treatment

• A nationwide cohort study found that high-intensity statin treatment after ischemic stroke was associated with similar risks of most effectiveness outcomes, including stroke recurrence, compared to moderate-intensity statin treatment 5.
• However, high-intensity statin treatment was associated with a reduced risk of all-cause mortality and an increased risk of diabetes 5.
• A meta-analysis of randomized trials found that each 1 mmol/L (39 mg/dL) decrease in low-density lipoprotein cholesterol equates to a reduction in relative risk for stroke of 21.1% 6.

Safety of Statin Therapy in Patients with Hemorrhagic Stroke

• A study found that statin therapy in patients with acute intracerebral hemorrhage (ICH) with dyslipidemia can decrease mortality, with a reduced risk of 10-year mortality in patients who experienced acute hemorrhagic stroke 7.
• However, the safety of statin therapy in patients with hemorrhagic stroke is still a concern, and more research is needed to fully understand the benefits and risks of statin therapy in this population 3, 7.

Recommendations for Statin Therapy

• Statins are recommended for the primary prevention of ischemic stroke in patients estimated to have a high 10-year risk for cardiovascular events 6.
• Statins are also recommended among patients with ischemic stroke or TIA presumed to be of atherosclerotic origin or with other comorbid atherosclerotic cardiovascular disease 6.
• The choice of statin and intensity of therapy should be individualized based on the patient's risk factors, medical history, and potential safety concerns 3, 5.