What is the effect of statins (HMG-CoA reductase inhibitors) on stroke?

From the Guidelines

Statins should be prescribed for the primary prevention of ischemic stroke in patients estimated to have a high 10-year risk for cardiovascular events, as they reduce the risk of stroke by approximately 21%. This recommendation is based on the guidelines for the primary prevention of stroke from the American Heart Association/American Stroke Association 1. The use of statins has been shown to decrease the risk of all strokes by ≈21% (95% CI, 15–27) in a meta-analysis of 26 trials that included >90,000 patients 1.

Key Points

• Statins reduce the risk of stroke in patients with or at high risk for atherosclerosis
• The risk of all strokes is estimated to decrease by 15.6% (95% CI, 6.7–23.6) for each 10% reduction in LDL cholesterol
• The intensity of cholesterol lowering does not correlate with the risk of intracerebral hemorrhage (ICH)
• Statins should be prescribed in accordance with the 2013 “ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults” 1

Benefits of Statins

• Reduce progression or induce regression of atherosclerosis
• Slow the progression of carotid intima-media thickness (IMT)
• Improve plaque characteristics, such as depleting carotid plaque lipid and reducing carotid plaque inflammation
• Enhance cerebral blood flow and reduce oxidative stress in the brain

Other Lipid-Modifying Therapies

• The benefits of lipid-modifying therapies other than statins on the risk of ischemic stroke are not established
• Niacin increases HDL cholesterol and decreases plasma levels of lipoprotein(a) [Lp(a)], but its efficacy in preventing ischemic stroke is not established and it has serious safety concerns, such as an increased risk of myopathy 1
• Fibric acid derivatives lower triglyceride levels and increase HDL cholesterol, but their efficacy in preventing stroke is not established 1

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 effect of statins (HMG-CoA reductase inhibitors) on stroke is to reduce the risk of stroke, including both fatal and non-fatal stroke, in adults with multiple risk factors for coronary heart disease (CHD) and in adults with type 2 diabetes mellitus with multiple risk factors for CHD 2, 2.

• Key benefits include reducing the risk of stroke in adults with multiple risk factors for CHD and in adults with type 2 diabetes mellitus.
• Main uses of statins include reducing the risk of myocardial infarction, stroke, and other cardiovascular events.

From the Research

Effect of Statins on Stroke

• The effect of statins on stroke is not directly addressed in the provided studies, but the impact of statins on cardiovascular events, including stroke, can be inferred from the available evidence 3, 4, 5, 6, 7.
• Statins have been shown to reduce the risk of cardiovascular events, including coronary heart disease and stroke, by lowering LDL-cholesterol levels 3, 4, 5.
• The addition of ezetimibe to statin therapy has been found to further reduce LDL-cholesterol levels and decrease the risk of cardiovascular events, including stroke 5, 6, 7.
• A study comparing ezetimibe/simvastatin with atorvastatin found similar effects on achieving target LDL-cholesterol levels in patients with very high risk, but did not specifically address the effect on stroke 6.
• Another study found that atorvastatin and ezetimibe/simvastatin had similar major cardiovascular outcomes, including stroke, in patients with type 2 diabetes and extremely atherosclerotic risks 7.

Mechanism of Action

• Statins work by inhibiting the synthesis of cholesterol in the liver, which leads to a decrease in LDL-cholesterol levels 3, 4, 5.
• Ezetimibe, on the other hand, inhibits the absorption of cholesterol in the intestine, which also leads to a decrease in LDL-cholesterol levels 4, 5, 6.
• The combination of ezetimibe and statin therapy has been found to have a synergistic effect on reducing LDL-cholesterol levels and decreasing the risk of cardiovascular events, including stroke 5, 6, 7.

Clinical Implications

• The use of statins, with or without ezetimibe, is a common strategy for reducing the risk of cardiovascular events, including stroke, in patients with high cardiovascular risk 3, 4, 5, 6, 7.
• The choice of statin and ezetimibe therapy should be based on individual patient characteristics, including their level of cardiovascular risk and their ability to tolerate the medications 5, 6, 7.