EVOlocumab in Stable Heart Failure With Reduced Ejection Fraction of Ischemic Etiology: EVO-HF Pilot

Sponsor
Fundació Institut Germans Trias i Pujol
Study ID
NCT03791593
Phase
PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Evolocumab — DRUG
    Evolocumab is a human IgG2 monoclonal antibody, it will add to patient treatment during 12 months.

Study Details

Evolocumab has been able to reduce the incidence of cardiovascular events in patients that had at least one cardiovascular risk factor \[28\]. In patients with chronic HFrEF, as we mentioned before, treatment with statins is not recommended as it has not shown benefits in improving its prognosis. However, CAD control stands as an approach that could improve the course of the disease by preventing microlesions that further weaken the heart. A recent multicenter study, the BIOSTAT-CHF \[3436\], was performed to determine whether the PCSK9-LDLR axis could predict risk in patients with HF. A multivariate analysis, which included BIOSTAT risk scores, LDLR, and statin treatment as covariates, revealed a positive linear association between PCSK9 levels and the risk of mortality and the composite endpoint (death or HF-related hospitalization). A similar analysis for LDLR revealed a negative association with mortality and the composite endpoint. Future studies must assess whether PCSK9 inhibition will result in better outcomes in HF. There is an unmet clinical need: blockade of the neurohormonal activation has provided advances in patients with HFrEF, yet mortality and morbidity remain unacceptably high. Approaching a strict control of lipid levels and CAD with evolocumab in stable HFrEF of ischemic ethology may represent a complementary pathophysiological pathway to reduce mortality and morbidity. The burden of CAD provides a solid rationale for testing the value of evolocumab in HF patients. Therefore, a pilot trial is proposed to evaluate the beneficial effect of evolocumab by surrogate biological markers before considering an event analysis study. Evolocumab reduces the risk of cardiovascular events in patients with established atherosclerotic disease, so this drug could play a role in HFrEF of ischemic etiology, by limiting macro- and micro-vascular coronary disease progression. In HFrEF patients due to ischemic etiology, there is a continuous troponin release due to persistent myocyte injury, which has been associated with adverse outcomes. Our hypothesis is that evolocumab may have the potential to reduce circulating hs-TnT levels, as a surrogate of myocyte injury due to atheroma progression in HFrEF. A positive result in this EVO-HF Pilot study may lead to the set-up of a large-scale multicenter prospective and randomized events study analyzing the role of lipid-lowering treatment by means of evolocumab in HFrEF of ischemic etiology

Key Dates

Start date
Dec 3, 2018
Status verified
Feb 2023
Primary completion
Jun 30, 2021
Completion
Jul 20, 2022

Study Design

Enrollment
46 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Experimental group
    The patient will receive evolocumab 420 mg/month on top of guideline-driven medical treatment
  • No Intervention: Control group
    The patient will continue guideline-driven medical treatment

Primary Outcome Measure

Change in hs-TnT levels at 1 year [ Time Frame: at 12 months of follow-up ]

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