What is the recommended statin regimen for patients who have had a stroke to reduce the risk of another cardiovascular event?

From the Guidelines

For patients who have had a stroke, high-intensity statin therapy with atorvastatin 80 mg daily is recommended to reduce the risk of recurrent cardiovascular events, as supported by the most recent guidelines 1. The preferred regimen is either atorvastatin 80 mg daily, as indicated in the 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack 1.

• The target LDL-cholesterol level in patients with ischemic stroke and TIA should be < 1.8 mmol/L (70 mg/dL) 1.
• Ezetimibe can be added to Atorvastatin to reach this goal, especially in patients with atherosclerotic disease of the extracranial or intracranial arteries 1.
• For patients who cannot tolerate high-intensity statins due to side effects, moderate-intensity statins such as atorvastatin 10-20 mg, rosuvastatin 5-10 mg, simvastatin 20-40 mg, or pravastatin 40-80 mg daily can be considered.
• It's essential to monitor liver function tests at baseline, 4-12 weeks after initiation, and periodically thereafter, as well as creatine kinase levels if muscle symptoms develop. The lipid-lowering effect of statins, along with their pleiotropic effects including improved endothelial function, reduced inflammation, and stabilization of atherosclerotic plaques, contributes to the reduction in stroke recurrence and other cardiovascular events, as demonstrated in studies such as the SPARCL trial 1.
• The SPARCL trial found that atorvastatin 80 mg daily reduced stroke recurrence in patients without another indication for statin therapy 1.
• The TST trial confirmed that target LDL-C <70 mg/dL was superior to a target of 90 to 110 mg/dL for preventing major cardiovascular events 1.

From the FDA Drug Label

In Study 4S, patients were treated with standard care, including lipid-lowering diet, and randomized to either simvastatin 20-40 mg/day (n=2,221) or placebo (n=2,223) for a median duration of 5.4 years. Simvastatin significantly reduced the risk of fatal plus non-fatal cerebrovascular events (combined stroke and transient ischemic attacks) by 28% (p=0. 033,75 vs 102 patients). The Heart Protection Study (Study HPS) was randomized, placebo-controlled, double-blind, multi-centered study with a mean duration of 5 years conducted in 10,269 patients on simvastatin 40 mg and 10,267 on placebo). Table 5: CHD Mortality and Cardiovascular Events in Adult Patients with High Risk of Developing a Major Coronary Event in Study HPS

• n = number of patients with indicated event Endpoint Simvastatin (N=10,269) n (%)* Placebo (N=10,267) n (%)* Risk Reduction (%) (95% CI) p-Value ... Stroke 444 (4.3%) 585 (5.7%) 25 (15 to 34%) p<0.0001 In the CARE study, the effect of pravastatin, 40 mg daily, on CHD death and nonfatal MI was assessed in 4,159 patients (3,583 men and 576 women) who had experienced a MI in the preceding 3 to 20 months and who had normal (below the 75th percentile of the general population) plasma total cholesterol levels. Table 8: CARE - Primary and Secondary Endpoints Number (%) of Subjects Event Pravastatin 40 mg (N=2,081) Placebo (N=2,078) Risk Reduction p-value ... Stroke or TIA 93 (4.5%) 124 (6.0%) 26% 0. 029

The recommended statin regimen for patients who have had a stroke to reduce the risk of another cardiovascular event is simvastatin 40 mg/day or pravastatin 40 mg/day, as these dosages have been shown to significantly reduce the risk of stroke and other cardiovascular events in patients with a history of stroke or at high risk of developing a major coronary event 2, 3.

• Key benefits of these statin regimens include:
  • Reduced risk of fatal and non-fatal cerebrovascular events
  • Reduced risk of CHD mortality and major coronary events
  • Improved lipid profiles, including decreased total cholesterol, LDL-C, and triglycerides, and increased HDL-C.

From the Research

Statin Regimen for Patients After a Stroke

The recommended statin regimen for patients who have had a stroke to reduce the risk of another cardiovascular event is a topic of ongoing research. Key findings from recent studies include:

• High-intensity statin therapy is often recommended for high-risk stroke patients to reduce the risk of stroke recurrence 4, 5, 6.
• However, the use of high-intensity statins may not always be necessary or appropriate for all patients, and moderate-intensity statins with ezetimibe may be a viable alternative 4.
• The choice of statin regimen should be individualized based on the patient's risk factors, medical history, and tolerance to different medications 7, 8.

Key Considerations

Some key considerations when selecting a statin regimen for patients after a stroke include:

• The patient's risk of future cardiovascular events, including stroke recurrence and myocardial infarction 5, 6.
• The patient's tolerance to different medications, including potential side effects and interactions 4, 7.
• The use of combination therapy, such as statins with ezetimibe, to achieve optimal lipid-lowering effects 4, 8.

Study Findings

Recent studies have reported the following findings:

• A randomized clinical trial found that moderate-intensity statin with ezetimibe was associated with a higher achievement rate of LDL-C targets and a greater reduction in LDL-C levels compared to high-intensity statin therapy 4.
• A nationwide cohort study found that high-intensity statin therapy was associated with a slightly reduced risk of all-cause mortality, but an increased risk of diabetes, compared to moderate-intensity statin therapy 5.
• Another nationwide cohort study found that more intense initial statin treatment was associated with improved long-term outcomes, including a lower risk of recurrent stroke and cardiovascular death 6.