What is the benefit of Crestor (Rosuvastatin) with Repatha (Evolocumab)?

From the Guidelines

Combining Crestor (rosuvastatin) with Repatha (evolocumab) can provide a significant reduction in LDL cholesterol levels, with Repatha reducing LDL-C by an additional 64% when administered at a dose of 140 mg every 2 weeks 1. This combination is particularly beneficial for patients with very high cholesterol levels, those with familial hypercholesterolemia, or individuals at high risk for cardiovascular events who haven't achieved target cholesterol levels with statins alone. The mechanism of action of Crestor involves reducing cholesterol production in the liver, while Repatha, a PCSK9 inhibitor, increases the liver's ability to remove LDL cholesterol from the blood. Key considerations for this combination therapy include:

• Monitoring for potential side effects such as injection site reactions with Repatha and muscle pain with Crestor
• Regular lipid panel testing to assess the effectiveness of this combination therapy
• Considering the cost and potential need for prior authorization for Repatha
• Advising latex-sensitive patients that the needle covers on the Repatha products contain latex 1. When used together, these medications can achieve greater LDL cholesterol reductions than either medication alone, which can lead to a reduced risk of cardiovascular events, as demonstrated by the FOURIER trial, which showed that the addition of evolocumab to statin therapy reduced the primary endpoint of CV death, MI, stroke, revascularization, or hospitalization for unstable angina 1.

From the FDA Drug Label

To reduce the risk of major adverse cardiovascular (CV) events (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization) in adults with established cardiovascular disease As an adjunct to diet, alone or in combination with other low-density lipoprotein cholesterol (LDL-C)-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C

The benefit of Crestor (Rosuvastatin) with Repatha (Evolocumab) is to reduce the risk of major adverse cardiovascular events and to lower LDL-C levels in adults with established cardiovascular disease or primary hyperlipidemia, including HeFH, as an adjunct to diet and other LDL-C-lowering therapies 2.

• The combination can be used to reduce the risk of CV events such as CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization.
• It can also be used to reduce LDL-C levels in adults with primary hyperlipidemia, including HeFH.

From the Research

Benefits of Combination Therapy

The combination of Crestor (Rosuvastatin) and Repatha (Evolocumab) may offer several benefits, including:

• Enhanced lipid-lowering effects: The combination of a statin (such as rosuvastatin) and a PCSK9 inhibitor (such as evolocumab) can lead to significant reductions in low-density lipoprotein cholesterol (LDL-C) levels 3, 4.
• Improved cardiovascular outcomes: Reducing LDL-C levels can help prevent cardiovascular events and improve atherosclerotic plaques 4.
• Increased likelihood of achieving LDL-C goals: Combination therapy with a statin and a non-statin LDL-C-lowering drug (such as evolocumab) can increase the number of patients who achieve their LDL-C goals 4.

Mechanisms of Action

The combination of rosuvastatin and evolocumab works by targeting different pathways in lipid metabolism:

• Rosuvastatin inhibits HMG-CoA reductase, reducing cholesterol synthesis in the liver 5, 6.
• Evolocumab inhibits PCSK9, increasing the liver's ability to remove LDL from the bloodstream 3, 4.
• The combination of these two mechanisms can lead to significant reductions in LDL-C levels and improved cardiovascular outcomes 3, 4.

Clinical Evidence

Several studies have demonstrated the efficacy and safety of combination therapy with rosuvastatin and ezetimibe, another lipid-lowering drug:

• A fixed-dose combination of rosuvastatin and ezetimibe has been shown to reduce LDL-C levels by up to 60-75% 5, 6.
• Combination therapy with rosuvastatin and ezetimibe has been associated with a good safety profile and improved adherence to medication 5, 6.
• While there is limited direct evidence on the combination of rosuvastatin and evolocumab, the available data suggest that this combination may offer similar benefits to combination therapy with rosuvastatin and ezetimibe 3, 4.