Amgen's Repatha Phase 3 VESALIUS-CV Trial Data to be Presented at AHA 2025

Analysis reveals significant industry trends and economic implications

Release Date

2025-11-03

Category

Clinical Trial Event

Reference

Source

Breakthrough Clinical Results

Amgen announced that new data from its cardiovascular portfolio, including results from the Phase 3 VESALIUS-CV clinical trial of Repatha (evolocumab), will be presented at the American Heart Association Scientific Sessions in November 2025. The VESALIUS-CV trial met its dual primary endpoints, demonstrating that Repatha significantly reduces the risk of major adverse cardiovascular events (MACE) in individuals without a prior history of heart attack or stroke. Real-world data from the REPATHA-CE trial also demonstrates its effectiveness in reducing MACE in clinical practice.

Key Highlights

  • Repatha VESALIUS-CV trial met dual primary endpoints, reducing CV events in high-risk patients without prior heart attack or stroke.
  • Repatha is the first and only PCSK9 inhibitor to demonstrate an improvement over optimal lipid-lowering therapy to prevent a first heart attack or stroke.
  • Real-world evidence from the Repatha-CE trial reinforces its position as a leading LDL-C lowering therapy for reducing cardiovascular events.
  • Amgen is committed to advancing both the science and the system of CV care.

Incidence and Prevalence

Global Cardiovascular Disease Burden: Latest Estimates

Prevalence

Cardiovascular diseases (CVDs) remain the leading cause of mortality and morbidity globally. According to recent data, CVD affects over 523 million people worldwide, making it the leading cause of global deaths. The global crude prevalence of CVD is estimated at 6.6%, while age-standardized estimates are around 6.3%.

Prevalent cases of total CVD have nearly doubled from 271 million in 1990 to 523 million in 2019. Specifically, in 2019, there were 197 million prevalent cases of ischemic heart disease and 101 million prevalent cases of stroke.

The prevalence of heart failure is increasing due to population aging and worldwide spreading of risk factors. A systematic review of heart failure studies from 1990 to 2020 found that prevalence ranged from 0.2% to 17.7%, with the highest rate observed in a US study of Medicare beneficiaries aged 65+ from 2002 to 2013.

Incidence

Globally, CVD incident cases increased by 77.12% from 31.31 million in 1990 to 55.45 million in 2019. Despite this increase in absolute numbers, the overall age-standardized incidence rate (ASIR) of CVD decreased between 1990-2019 with an estimated annual percentage change of -0.56.

For stroke, there were 11.9 million incident strokes globally in 2021. Of these, ischemic stroke constituted 65.3%, intracerebral hemorrhage constituted 28.8%, and subarachnoid hemorrhage constituted 5.8%.

The incidence of heart failure ranged from 0.1% to 4.3%, with the highest rate in a US study of Medicare beneficiaries 65+ from 1994 to 2003.

Regional Variations

The number of CVD incident cases increased remarkably in low (108.3%), low-middle (114.81%), and middle (117.85%) sociodemographic index regions between 1990-2019.

Against the global trend of falling ASIR, some countries showed increasing trends, including Uzbekistan (EAPC, 1.24), Tajikistan (EAPC, 0.49), and Zimbabwe (EAPC, 0.42).

Regional differences in heart failure patient characteristics were observed across Western Europe, Central/Eastern Europe, North America, Latin America, and Asia-Pacific, with varying prevalence of comorbidities and outcomes.

The Asian Region had an estimated 22,246,127 cases of rheumatic heart disease in 2019 and 249,830 deaths.

Mortality

The number of CVD deaths steadily increased from 12.1 million in 1990, reaching 18.6 million in 2019, accounting for 32% of all deaths worldwide. Ischemic heart disease was the leading cause of death globally, followed by stroke.

Heart failure accounts for approximately 36% of all CVD-related deaths and stands as the foremost cause of hospitalization. One-year heart failure case fatality ranged from 4% to 45% with an average of 33% overall.

Stroke is a major contributor to cardiovascular mortality, with approximately 5 million fatalities occurring annually.

Despite the increase in absolute numbers, the overall age-standardized mortality rate (ASMR) decreased globally from 1990 to 2019, though the CVD burden continues to rise in almost all countries outside high-income regions.

Recent Studies

Recent Cardiovascular Disease Studies: Interventions, Safety, and Efficacy

ODYSSEY OUTCOMES (2021)

  • Intervention: PCSK9 inhibitor alirocumab
  • Efficacy: Decreased LDL-C by 48.5% vs. placebo; reduced risk of primary outcome (coronary heart disease death, non-fatal myocardial infarction, ischemic stroke, or unstable angina); fewer deaths observed in the alirocumab group; significant benefit in patients with eGFR ≥60 mL/min/1.73 m² but not in those with eGFR <60
  • Safety: Adverse events other than local injection-site reactions were similar across all eGFR categories

ASTERIAS Trial (2020)

  • Intervention: Triflusal versus aspirin
  • Efficacy: Equivalent efficacy between treatments for the primary endpoint (composite of MI, stroke, or death from vascular causes); triflusal significantly reduced the incidence of MI
  • Safety: Patients on triflusal were 50% less likely to develop bleeding events; showed a better safety profile compared with aspirin

Tirofiban Study (2021)

  • Intervention: Tirofiban versus aspirin plus clopidogrel
  • Efficacy: Tirofiban alone was noninferior to dual antiplatelet therapy for primary outcome (90-day modified Rankin Scale); mortality at 90 days was 8% in tirofiban group vs 10% in dual antiplatelet group
  • Safety: No difference in ICH rate between groups; tirofiban appeared safe as monotherapy

Vitamin K2 and D Supplementation Study (2023)

  • Intervention: Vitamin K2 (720 μg/day) and D (25 μg/day)
  • Efficacy: No significant reduction in mean coronary artery calcification progression overall; significant benefit in patients with CAC scores ≥400 AU
  • Safety: Safety events were fewer in participants receiving supplementation (1.9% vs 6.7%)

CEAG Supplement Study (2019)

  • Intervention: Curcumin, Eicosapentaenoic acid, Astaxanthin and Gamma-linoleic acid
  • Efficacy: Significant reduction in mean systolic blood pressure at 4 weeks compared to placebo; significant decrease in High sensitivity C Reactive Protein; blunted increase in IL-6
  • Safety: Not specifically mentioned in the context

Aleglitazar Study (2014)

  • Intervention: Aleglitazar
  • Efficacy: Did not reduce the risk of cardiovascular outcomes in patients with type 2 diabetes and recent ACS
  • Safety: Increased rates of serious adverse events, including heart failure, gastrointestinal hemorrhages, and renal dysfunction

Antiplatelet Therapy Studies (2021-2022)

  • Intervention: Dual loading dose of antiplatelet therapy; Ticagrelor vs. clopidogrel
  • Efficacy: No decreased MACE risk among elderly ACS patients; similar risk of in-hospital MACE
  • Safety: Increased major bleeding risk in elderly patients; ticagrelor showed 45% higher risk of in-hospital major bleeding compared to clopidogrel