Is a patient with hyperlipidemia and intolerance to statin (HMG-CoA reductase inhibitor) therapy a candidate for Repatha (evolocumab)?

Is This Patient a Candidate for Repatha (Evolocumab)?

Yes, this patient with statin intolerance is a candidate for Repatha (evolocumab), but only after first trying ezetimibe and potentially bempedoic acid, depending on their cardiovascular risk level and LDL-C response to initial therapy. 1, 2

Current Lipid Profile Assessment

Your patient's lipid values show:

• Total cholesterol: 203 mg/dL
• Triglycerides: 224 mg/dL (elevated)
• LDL-C: 124 mg/dL (above goal for most risk categories)
• Calculated non-HDL-C: 158 mg/dL (203 - 45 = 158, assuming HDL ~45)

The elevated triglycerides (224 mg/dL) and LDL-C of 124 mg/dL indicate this patient needs additional lipid-lowering therapy beyond what statins would have provided. 1

Treatment Algorithm for Statin-Intolerant Patients

Step 1: Confirm True Statin Intolerance

Before proceeding, verify the patient has attempted at least 2 different statins, including at least one at the lowest approved daily dose, with adverse effects that resolved or improved upon discontinuation. 2, 3 This is critical because many patients labeled as "statin intolerant" can actually tolerate alternative statins, lower doses, or non-daily dosing. 1

Step 2: Initiate Ezetimibe First

Start with ezetimibe 10 mg daily as the first-line non-statin therapy. 2, 3 This will reduce LDL-C by approximately 15-20% and is well-tolerated with minimal side effects. 1, 3 For this patient with LDL-C of 124 mg/dL, ezetimibe alone would bring LDL-C down to approximately 99-105 mg/dL.

Reassess lipid profile at 4-8 weeks after starting ezetimibe. 2, 3

Step 3: Determine Cardiovascular Risk Category

The decision to add Repatha depends heavily on the patient's cardiovascular risk:

Very High-Risk Patients (established ASCVD, recent ACS, recurrent events):

• Target LDL-C: <55 mg/dL with ≥50% reduction from baseline 1, 2
• If LDL-C remains ≥55 mg/dL on ezetimibe, add bempedoic acid 180 mg daily (provides additional 15-25% LDL-C reduction) 1, 2
• If LDL-C still ≥55 mg/dL despite ezetimibe + bempedoic acid, then add Repatha 1, 2

High-Risk Patients (diabetes with target organ damage, severe single risk factor, 10-year ASCVD risk ≥20%):

• Target LDL-C: <70 mg/dL 1, 2
• If LDL-C remains ≥70 mg/dL on ezetimibe, add bempedoic acid 180 mg daily 1, 2
• Consider Repatha only if LDL-C remains significantly elevated after ezetimibe + bempedoic acid 1, 2

Moderate-Risk Patients (10-year ASCVD risk 7.5-20%):

• Target LDL-C: <100 mg/dL or ≥50% reduction 2
• Add bempedoic acid if needed after ezetimibe 2
• PCSK9 inhibitors like Repatha do NOT have an established role in primary prevention at moderate risk 2

Step 4: When Repatha Is Appropriate

Repatha is FDA-approved and guideline-recommended for statin-intolerant patients when: 1, 4

1. Primary hyperlipidemia/mixed dyslipidemia as adjunct to diet, alone or with other lipid-lowering therapies 4
2. Established ASCVD to reduce MI, stroke, and coronary revascularization risk 4
3. Heterozygous or homozygous familial hypercholesterolemia 4

Dosing options: 1, 4

• 140 mg subcutaneously every 2 weeks, OR
• 420 mg subcutaneously once monthly

Expected LDL-C reduction: approximately 50-60% 1, 2, 4

Evidence Supporting Repatha in Statin-Intolerant Patients

The ODYSSEY ALTERNATIVE trial demonstrated that PCSK9 inhibitors (alirocumab, similar mechanism to evolocumab) reduced LDL-C by 54.8% in statin-intolerant patients, with fewer skeletal muscle-related adverse events (32.5%) compared to ezetimibe (41.1%) or atorvastatin rechallenge (46%). 1 This suggests excellent tolerability in this population.

The FOURIER trial showed that evolocumab reduced major cardiovascular events by 15% in patients with established ASCVD, with a monotonic relationship between LDL-C reduction and clinical benefit even down to very low LDL-C levels (<25 mg/dL). 4, 5 Safety was excellent even at these very low LDL-C levels. 5

Important Caveats and Pitfalls

Triglyceride Consideration

With triglycerides of 224 mg/dL, this patient has moderate hypertriglyceridemia. 1 While Repatha will address the LDL-C, consider:

• Lifestyle modifications (weight loss, reduced refined carbohydrates, alcohol restriction) 2
• If triglycerides remain 135-499 mg/dL despite therapy and patient is high-risk with established ASCVD, consider adding icosapent ethyl for additional cardiovascular risk reduction 2
• If triglycerides exceed 500 mg/dL, prioritize fibrate therapy to prevent acute pancreatitis before focusing on LDL-C 2

Cost and Access Barriers

PCSK9 inhibitors are expensive. Try ezetimibe (generic available) and bempedoic acid first unless the patient has very high risk with markedly elevated LDL-C. 1, 2 The 2022 ACC Expert Consensus specifically recommends this stepwise approach to balance efficacy, safety, and cost. 1

Monitoring Requirements

Once on Repatha: 2

• Assess LDL-C response every 3-6 months initially
• Once at goal, annual lipid monitoring is sufficient
• Monitor for injection site reactions (generally mild) 4

When to Refer to Lipid Specialist

Consider referral if: 2

• Baseline LDL-C ≥190 mg/dL not due to secondary causes
• Complex mixed dyslipidemia
• Severe hypertriglyceridemia (>500 mg/dL)
• Suspected familial hypercholesterolemia

Bottom Line for This Patient

Start with ezetimibe 10 mg daily now. 2, 3 Reassess in 4-8 weeks. If the patient has established ASCVD (very high-risk) and LDL-C remains elevated, add bempedoic acid next. 1, 2 Repatha becomes appropriate if LDL-C goals are still not met after ezetimibe ± bempedoic acid, particularly if the patient has established cardiovascular disease. 1, 2, 4 For primary prevention without very high baseline LDL-C (≥190 mg/dL) or familial hypercholesterolemia, Repatha's role is less established and should be reserved for cases where other therapies have failed. 2