Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT03791593 |
Other study ID # |
ICOR-2016-05 |
Secondary ID |
2017-004656-30 |
Status |
Completed |
Phase |
Phase 2
|
First received |
|
Last updated |
|
Start date |
December 3, 2018 |
Est. completion date |
July 20, 2022 |
Study information
Verified date |
February 2023 |
Source |
Fundació Institut Germans Trias i Pujol |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial 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
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.