What is the efficacy of Repatha (evolocumab) in treating atherosclerosis in coronary, peripheral, and carotid arteries?

Efficacy of Repatha (Evolocumab) in Treating Atherosclerosis

Repatha (evolocumab) demonstrates robust efficacy in reducing cardiovascular events across all major arterial beds in patients with established atherosclerotic cardiovascular disease, with the strongest evidence supporting a 20% reduction in cardiovascular death, myocardial infarction, or stroke when added to statin therapy. 1

Coronary Artery Disease Efficacy

In patients with coronary atherosclerosis, evolocumab reduces major adverse cardiovascular events by 15% and the composite of cardiovascular death, MI, or stroke by 20%. 2, 1

• The landmark FOURIER trial enrolled 27,564 patients with established atherosclerotic disease and demonstrated that evolocumab reduced LDL cholesterol by 59% (from median 92 mg/dL to 30 mg/dL) over 2.2 years of follow-up 2, 1
• The primary composite outcome (cardiovascular death, MI, stroke, hospitalization for angina, or revascularization) occurred in 9.8% of evolocumab patients versus 11.3% of placebo patients (15% relative risk reduction, P<0.001) 2, 1
• Importantly, patients with diabetes showed consistent benefits, comprising 40% of the FOURIER trial population (11,031 patients), with similar relative risk reductions 2
• Extended follow-up data demonstrate incremental cardiovascular risk reductions over time, including a 23% reduction in cardiovascular mortality with no apparent LDL-C threshold below which further risk reduction ceases 3

Cerebrovascular (Carotid) Disease Efficacy

Evolocumab specifically reduces stroke risk by 21-25% in patients with atherosclerotic disease, with consistent effects in patients with or without prior ischemic stroke. 2

• All strokes were reduced from 1.9% to 1.5% (HR 0.79,95% CI 0.66-0.95, P=0.01) in the FOURIER trial 2
• Ischemic stroke specifically was reduced by 25% (from 1.6% to 1.2%; HR 0.75,95% CI 0.62-0.92, P=0.005) 2
• The stroke reduction benefit was consistent across all major subgroups, including those with and without baseline history of ischemic stroke 2
• In the context of carotid atherosclerotic disease management, evolocumab represents a critical component of triple medical therapy (antithrombotic, antihypertensive, and LDL-C lowering) that reduces stroke, MI, and death 2

Peripheral Artery Disease Efficacy

While the FOURIER trial included patients with symptomatic peripheral artery disease as part of the high-risk atherosclerotic disease population, evolocumab demonstrated consistent cardiovascular event reduction across all vascular territories. 1, 3

• Patients with peripheral artery disease represented a subset of the very high-risk population that derived enhanced absolute benefits from evolocumab therapy 3
• The composite cardiovascular outcomes (death, MI, stroke, revascularization) were reduced consistently regardless of the specific arterial bed involved 1

Primary Prevention in High-Risk Patients Without Prior Events

The recent VESALIUS-CV trial (2025) extends evolocumab's proven efficacy to patients with atherosclerosis or diabetes without prior MI or stroke, demonstrating a 25% reduction in 3-point MACE and 19% reduction in 4-point MACE. 4

• Among 12,257 patients followed for median 4.6 years, 3-point MACE occurred in 6.2% of evolocumab patients versus 8.0% of placebo patients (HR 0.75,95% CI 0.65-0.86, P<0.001) 4
• 4-point MACE (including revascularization) occurred in 13.4% versus 16.2% (HR 0.81,95% CI 0.73-0.89, P<0.001) 4
• This represents a critical expansion of evidence to lower-risk atherosclerotic populations 4

Safety Profile and Long-Term Use

Evolocumab demonstrates an excellent safety profile with no significant adverse events except injection-site reactions, even at very low achieved LDL-C levels. 1, 3

• No significant differences in adverse events including new-onset diabetes or neurocognitive events were observed between evolocumab and placebo groups 1
• Injection-site reactions were more common with evolocumab (2.1% vs 1.6%) but remained low overall 1
• Real-world evidence demonstrates treatment persistence rates exceeding 90% and confirms the favorable safety profile even at the lowest LDL-C levels achieved 3
• Long-term follow-up extending to 8.4 years shows maintained LDL-C reductions and continued safety 3

Clinical Application Algorithm

For patients with established atherosclerotic disease in any vascular bed (coronary, carotid, or peripheral) who remain above LDL-C targets despite maximally tolerated statin therapy:

1. Add evolocumab 140 mg subcutaneously every 2 weeks (or 420 mg monthly) to achieve LDL-C <55 mg/dL with ≥50% reduction from baseline 2, 5
2. Expect approximately 59% LDL-C reduction with median achieved levels around 30 mg/dL 2, 1
3. Anticipate 15-25% relative risk reduction in major cardiovascular events depending on baseline risk profile 1, 4
4. Monitor for injection-site reactions as the primary adverse effect 1

For patients with diabetes and atherosclerosis or high cardiovascular risk, evolocumab provides particularly robust absolute risk reductions (2.3% absolute reduction in primary endpoint versus 1.2% in non-diabetic patients). 2

Important Caveats

• The cardiovascular benefits of evolocumab are additive to optimized statin therapy, not a replacement for it 2, 1
• Benefits accrue over time, with greater absolute risk reductions observed during extended follow-up periods 3
• There is a monotonic relationship between LDL-C reduction and clinical event reduction, with no lower threshold identified below which benefit ceases 1, 3
• Patients with recent acute coronary syndrome, multiple prior events, or peripheral artery disease derive enhanced absolute benefits 3