NCT03791593: EVO-HF

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

Completed Phase 2 Last updated 15 February 2023

What this trial tests

Phase 2 trial testing Evolocumab in Heart Failure With Reduced Ejection Fraction in 46 participants. Completed in 20 July 2022.

Timeline

3 December 2018

Primary endpoint
30 June 2021

20 July 2022

Quick facts

Lead sponsor	Fundació Institut Germans Trias i Pujol
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	46
Start date	3 December 2018
Primary completion	30 June 2021
Estimated completion	20 July 2022
Sites	3 locations across Spain

Drugs / interventions tested

• Evolocumab (EVOLOCUMAB) — full drug profile →

Conditions studied

• Heart Failure With Reduced Ejection Fraction — all drugs for Heart Failure With Reduced Ejection Fraction →

Sponsor

Fundació Institut Germans Trias i Pujol — full company profile →

Who can join

Adults 18 to 80, any sex, with Heart Failure With Reduced Ejection Fraction. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Proteome-wide mendelian randomization investigates potential associations in heart failure and its etiology: emphasis on PCSK9.
   Lin L, Yu H, Xue Y, Wang L, et al · · 2024 · cited 7× · PMID 38383373 · DOI 10.1186/s12920-024-01826-6