What is the cornerstone treatment for patients with hyperlipidemia?

From the Guidelines

The cornerstone treatment for patients with hyperlipidemia is statin therapy. Statins such as atorvastatin (10-80 mg daily), rosuvastatin (5-40 mg daily), simvastatin (10-40 mg daily), and pravastatin (10-80 mg daily) are the first-line medications due to their proven efficacy in reducing LDL cholesterol and cardiovascular events, as recommended by the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1. Treatment should be individualized based on cardiovascular risk assessment, with higher intensity statins (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) recommended for patients with established cardiovascular disease or high risk factors.

Key Considerations

• Statins work by inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, thereby reducing LDL cholesterol production in the liver and increasing LDL receptor expression, which enhances cholesterol clearance from the bloodstream.
• Lifestyle modifications including a heart-healthy diet low in saturated fats, regular physical activity (150 minutes of moderate-intensity exercise weekly), weight management, smoking cessation, and limited alcohol consumption should accompany medication therapy.
• Patients should be monitored with lipid panels 4-12 weeks after initiating therapy and periodically thereafter, with liver function tests to assess for potential side effects, as supported by the 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation 1.
• The goal of treatment is to lower LDL-C to <1.4 mmol/L (<55 mg/dL) and to reduce it by at least 50% if the baseline LDL-C level is 1.8-3.5 mmol/L (70-135 mg/dL), as recommended by the 2020 ESC guidelines 1.

Additional Recommendations

• If goal LDL-C cannot be reached through lifestyle and statins, other lipid-modifying therapies (such as PCSK9 inhibitors or ezetimibe) should be considered, following general recommendations 1.
• Treatment of other lipid aberrations, including high triglyceride and lipoprotein(a) levels, should follow general recommendations 1.

From the Research

Cornerstone Treatment for Hyperlipidemia

The cornerstone treatment for patients with hyperlipidemia is statin therapy, which has been shown to significantly reduce the risk of cardiovascular disease by lowering low-density lipoprotein cholesterol (LDL-C) levels 2, 3.

Key Benefits of Statin Therapy

• Statins have been found to reduce the relative risk of cardiovascular disease by 24-37%, regardless of age, sex, prior history of coronary heart disease (CHD), or other co-morbid conditions 2.
• Statin treatment can also be effective in people whose LDL-C is not considered elevated under current guidelines, as demonstrated in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) and the Collaborative Atorvastatin Diabetes Study (CARDS) 2.
• More intensive lipid-lowering regimens using statins, such as atorvastatin, can provide additional clinical benefits, including a decrease in atherogenic lipoproteins and atheroma volume in patients with established CHD 2.

Combination Therapy Options

• Combination therapy with a statin and other lipid-lowering agents, such as bile-acid sequestrants or the cholesterol-absorption inhibitor ezetimibe, can be used to achieve greater LDL cholesterol reductions 3.
• Niacin or fenofibrate can be added to a statin for treatment of mixed dyslipidemia 3.
• The combination of PCSK9 inhibitors with robust statins like rosuvastatin and atorvastatin has been shown to markedly decrease LDL-C levels in patients with hyperlipidemia 4.

Efficacy and Safety of Statins

• Rosuvastatin has been found to have superior efficacy in lowering LDL-C levels compared to other statins, with a mean reduction of 45-63% at daily doses of 5-40 mg 5.
• Statins have been shown to be safe and well-tolerated, with a similar safety profile to other lipid-lowering agents 5, 4.
• The incidence of adverse events with statin therapy is similar to that observed with placebo or potent statin groups, with no significant differences identified in some studies 4.