Is it common practice to use Repatha (evolocumab) and then add atorvastatin to the treatment regimen, given that Repatha availability could be reduced by 20 percent?

From the Guidelines

Combining Repatha (evolocumab) with atorvastatin is a common practice in lipid management, particularly in high-risk patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia, as supported by the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1. When patients have not achieved their LDL cholesterol targets with statin therapy alone, doctors typically add Repatha to the regimen. If Repatha availability is reduced by 20%, physicians might still maintain this combination but could consider adjusting the dosing schedule of Repatha (perhaps extending from every 2 weeks to every 3 weeks) while optimizing the atorvastatin dose. Alternatively, they might temporarily increase the atorvastatin dose while Repatha access is limited. This combination approach is physiologically sound because the medications work through complementary mechanisms - statins reduce cholesterol production in the liver, while Repatha enhances LDL receptor activity to remove more cholesterol from circulation. Some key points to consider in this approach include:

• The importance of a heart-healthy lifestyle across the life course, as emphasized in the guideline 1
• The use of high-intensity statin therapy or maximally tolerated statin therapy in patients with clinical ASCVD to reduce LDL-C levels by 50% 1
• The consideration of adding non-statins to statin therapy in very high-risk ASCVD patients, with a LDL-C threshold of 70 mg/dL (1.8 mmol/L) 1
• The potential benefits and risks of adjusting the dosing schedule of Repatha or temporarily increasing the atorvastatin dose, and the need for regular monitoring of lipid panels to ensure adequate cholesterol control during any period of limited Repatha availability. In terms of specific guidance, the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline recommends that in patients with severe primary hypercholesterolemia (LDL-C level ‡190 mg/dL [‡4.9 mmol/L]), without calculating 10-year ASCVD risk, high-intensity statin therapy should be started, and if the LDL-C level remains $100 mg/dL ($2.6 mmol/L), adding ezetimibe is reasonable, and if the LDL-C level on statin plus ezetimibe remains $100 mg/dL ($2.6 mmol/L) and the patient has multiple factors that increase subsequent risk of ASCVD events, a PCSK9 inhibitor may be considered 1. However, it's worth noting that the long-term safety (>3 years) of PCSK9 inhibitors is uncertain and economic value is low at mid-2018 list prices 1. In contrast, the study by 1 is older and focuses on the comparison of atorvastatin and pravastatin, which is not directly relevant to the current question of combining Repatha with atorvastatin. Therefore, the most recent and highest quality study, 1, should be prioritized in making clinical decisions. Patients should be monitored with regular lipid panels to ensure the modified regimen maintains adequate cholesterol control during any period of limited Repatha availability. Key considerations in this approach include:
• The importance of regular monitoring of lipid panels
• The need to adjust the dosing schedule of Repatha or temporarily increase the atorvastatin dose based on individual patient needs
• The potential benefits and risks of combining Repatha with atorvastatin, including the complementary mechanisms of action and the potential for improved cholesterol control.

From the Research

Treatment Regimen for Lowering Cholesterol

• The use of Repatha (evolocumab) in combination with atorvastatin is a common practice for intensive lipid-lowering therapy, as seen in studies such as 2 where evolocumab was added to atorvastatin and ezetimibe to strengthen lipid lowering in patients with extremely high-risk acute coronary syndrome.
• The study 2 found that the addition of evolocumab to atorvastatin and ezetimibe resulted in a significant reduction in LDL-C levels and improved cardiovascular prognosis.
• Another study 3 discusses the use of statins, ezetimibe, and evolocumab as a combination therapy for lowering cholesterol, highlighting the potential benefits of using these medications together to achieve optimal lipid-lowering effects.

Effectiveness of Combination Therapy

• The study 4 found that early combination therapy with atorvastatin and ezetimibe, followed by escalation with bempedoic acid or PCSK9 inhibitors, was effective in achieving recommended LDL-C targets in patients with ST-elevation myocardial infarction.
• The study 5 compared intensive lipid-lowering therapy with atorvastatin to moderate lipid-lowering therapy with pravastatin and found that the intensive therapy resulted in a greater reduction in LDL-C levels and a lower risk of major cardiovascular events.
• The study 6 also found that intensive lipid-lowering therapy with atorvastatin resulted in a significant reduction in major cardiovascular events in patients with stable coronary heart disease.

Reduction in Repatha Availability

• While the studies do not directly address the impact of a 20% reduction in Repatha availability, they do suggest that combination therapy with atorvastatin and other lipid-lowering medications can be effective in achieving optimal lipid-lowering effects, even if Repatha is not available at full capacity 4, 3, 2.