Repath (Evolocumab) Reduces Cardiovascular Event Risk in High-Risk Patients
Evolocumab (Repath) significantly reduces cardiovascular events by approximately 15% in patients with established atherosclerotic cardiovascular disease and residual hypercholesterolemia despite statin therapy. 1
Evidence for Cardiovascular Risk Reduction
Evolocumab is a monoclonal antibody that blocks PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9), producing rapid, potent, and sustained reduction of LDL cholesterol levels when used in combination with statin therapy 1
The FOURIER trial demonstrated that evolocumab significantly reduces the incidence of major adverse cardiovascular events by 15% (p<0.001) in patients with atherosclerotic cardiovascular disease and residual hypercholesterolemia despite statin therapy 1, 2
When added to statin therapy, evolocumab confers a 20% reduction in the composite endpoint of cardiovascular death, myocardial infarction, or stroke 2
During extended follow-up, evolocumab treatment resulted in a 23% reduction in cardiovascular mortality with no apparent LDL-C level below which there is no further cardiovascular risk reduction 2
Specific Patient Populations and Benefits
Patients with peripheral artery disease (PAD) show consistent benefits with evolocumab:
The absolute benefits of evolocumab are enhanced among various patient types at high and very high risk for secondary ASCVD, including those with:
- Recent myocardial infarction
- Multiple cardiovascular events
- Peripheral artery disease 2
Risk Stratification and Treatment Recommendations
For patients with very high risk (>20% five-year risk of major adverse cardiovascular events), guidelines suggest adding a second lipid-lowering drug, preferably ezetimibe first, followed by a PCSK9 inhibitor like evolocumab 4
For high-risk patients (15-20% five-year risk of MACE), guidelines suggest adding ezetimibe but recommend against adding a PCSK9 inhibitor to ezetimibe (strong recommendation) 4
For moderate-risk patients (5-15% five-year risk of MACE), guidelines suggest not using additional lipid-lowering drugs beyond statins, but if considering one, ezetimibe is preferred over PCSK9 inhibitors 4
For low-risk patients (<5% five-year risk of MACE), guidelines recommend against using additional lipid-lowering drugs 4
Safety Profile
Evolocumab has demonstrated an excellent safety profile, even in patients with very low LDL-C levels 1, 2
Real-world evidence shows a high treatment persistence rate of >90% with evolocumab 2
The only notable adverse effect is a small increase in local injection site reactions 2
Practical Considerations
Evolocumab is administered by subcutaneous injection every 2 weeks or monthly 4
Many patients may prefer oral medications to injectable drugs, which should be considered in treatment decisions 4
Regular blood samples or visits after starting evolocumab are encouraged to monitor adherence and potential adverse effects 4
Most patients will need to take this medication for the rest of their lives 4
Comparison to Other Cardiovascular Risk Reduction Strategies
For patients with elevated triglycerides, icosapent ethyl has shown cardiovascular risk reduction in the REDUCE-IT trial 5
Unlike evolocumab, which targets LDL-C, icosapent ethyl reduces cardiovascular risk in patients with elevated triglycerides (≥150 mg/dL) despite maximally tolerated statin treatment 5
SGLT2 inhibitors like empagliflozin have also demonstrated cardiovascular benefits, with empagliflozin reducing major adverse cardiovascular events by 14% and cardiovascular death by 38% in patients with type 2 diabetes and established cardiovascular disease 6