Effect of PCSK9 InhibitorS On Calcific Aortic Valve DiseasE
Status:
Recruiting
Trial end date:
2024-01-01
Target enrollment:
Participant gender:
Summary
Calcific Aortic Stenosis (CAS) can cause severe adverse cardiac events, but there is
currently no effective drug that can prevent or delay the progression of the disease, aortic
valve replacement is still the only therapy.
The epidemiology of CAS shows that it is related with level of Lp(a)、LDL-C and PCSK9. Several
observational studies indicate that the use of statins to decrease the level of LDL-C is
associated with the reduced incidence of CAS, but no Randomized Control Trials(RCTs) show
that statins have any benefit on the progression or clinical outcome of CAS，so the
investigators speculated that this may be related to the limited reduction of LDL-C by
statins therapy. The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor has
emerged as a new lipid-lowing drug. On the basis of statin treatment, it can further reduces
LDL-C and Lp(a) concentrations by 50% to 60% and 20% to 30%,respectively. Some studies report
that elevated plasma PCSK9 levels are related to CAS and PCSK9 R46L loss-of-function mutation
are associated with lower rates of CAS, and other observational studies found that PCSK9
inhibitors can reduce the incidence of CAS.
The research, on the basis of statins therapy, intends to study the effect of PCSK9
inhibitors on delaying or preventing patients with CAS. A total of 160 patients are planned
to be selected for the presence of CAS that are confirmed by echocardiography but currently
do not need valve replacement, and with the diagnosis of hypercholesterolemia. All of the
patients were followed at 4 weeks、24 weeks 、48 weeks and 96 weeks for a minimum of 2 years.
The primary endpoint is the average annual change in aortic-jet velocity. Secondary endpoints
include average annual change of aortic valve calcification score that measured by Computed
Tomography and major adverse cardiovascular events (cardiovascular death, non-fatal stroke or
non-fatal myocardial infarction). The outcomes of the study will provide new ideas for the
treatment of patients with CAS, and will also provide an important theoretical basis for the
expansion of the clinical indications of PCSK9 inhibitors and the exploration their
extra-lipid-lowering effects.