EVOlocumab in Stable Heart Failure With Reduced Ejection Fraction of Ischemic Etiology: EVO-HF Pilot
Condition: Heart Failure With Reduced Ejection Fraction
MeSH terms: Heart Failure
Study type: Interventional
Phase: Phase 2

Summary: 
      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
    

Detailed 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.

      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.

      Therefore, a pilot trial is proposed to evaluate the beneficial effect of evolocumab by
      surrogate biological markers before considering an event analysis study.
    

Intervention name(s): Evolocumab
Intervention type(s): Drug
Intervention description(s): Evolocumab is a human IgG2 monoclonal antibody, it will add to patient treatment during 12 months.
Other intervention name(s): Repatha
Intervention MeSH terms: Evolocumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment