Clinical trial NCT06648915: Lipoprotein(a) and Progression of Aortic Stenosis
Official title: Association of Lipoprotein(a) With Progression of Degenerative Aortic Valve Stenosis: Propensity-matched Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Aortic Valve Stenosis
Lipoprotein(a)
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2024-10-18
Enrollment: 364
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who underwent measurement of Lp(a) and had a diagnosis of mild to moderate, degenerative AVS between 2000 and 2020

Brief summary: This study is a prospective, observational, two arm parallel group, clinical study involving patients with measurements of Lp(a) and mild to moderate aortic stenosis. A total of 1381 patients underwent measurement of Lp(a) and had a diagnosis of mild to moderate, degenerative aortic stenosis between 2001 and 2020 in Asan Medical Center. Investigators selected a propensity-matched cohort of patients with Lp(a) \>70 mg/dL and those with Lp(a) \<30 mg/dL from the registry of patients with mild to moderate aortic stenosis to control risk factors for progression of aortic stenosis, and try to prospectively compare progression of aortic stenosis between the two groups (Lp(a) \>70 mg/dL versus Lp(a) \< 30 mg/dL). Investigators also evaluate interactions between Lp(a) groups and baseline clinical and echocardiographic variables for progression of aortic stenosis.

Detailed description: Observational and genetic studies suggest that high levels of lipoprotein(a) (Lp\[a\]) increase the risk of calcific aortic valve stenosis (AVS). With the advancements of novel, specific therapies targeting Lp(a), there has been a growing need for clinical trials evaluating the effect of Lp(a) lowering in AVS. Requirement of longer follow-up time, selection of target populations and estimation of effect size are challenging issues for conducting clinical trials in AVS, and previous trials of statin therapy, which included patients with mild to moderate AVS, showed no significant effect of lowering LDL-cholesterol on the progression of AVS. Although post hoc analyses of previous statin trials showed that elevated levels of Lp(a) was associated with faster AVS progression, Lp(a) was associated with initiation but not with progression of AV calcification in a population-based study including 922 individuals. Because of a critical logistical challenge to randomized trials focusing the pre-calcific stages of AV disease, a clinical trial testing the progression of preexisting AVS is more feasible. The Lp(a)FRONTIERS CAVS trial (Assessing the Impact of Lipoprotein(a) Lowering with Pelacarsen (TQJ230) on the Progression of Calcific AVS; NCT05646381) will determine if pelacarsen can slow down the progression of AVS in patients with mild to moderate calcific AVS compared to placebo. To ensure adequate power to test the hypothesis of the ongoing Lp(a)FRONTIERS CAVS trial, it is important to estimate differences in progression of AS according to Lp(a) levels. However, such information is lacking and a well-designed prospective observational study is needed to directly compare progression of AS between the target population (patients with Lp(a) \>70 mg/dL) of the Lp(a)FRONTIERS CAVS trial and control population (patients with mild to moderate AS and Lp(a) \<30 mg/dL).

Investigators' prospective registry, started in 2001 at Asan Medical Center, has included all consecutive patients with measurements of Lp(a) and echocardiographic diagnosis of AVS. A total of 1381 patients underwent measurement of Lp(a) and had a diagnosis of mild to moderate, degenerative AVS between 2001 and 2020. Of the 1381 patients, 831 had Lp(a) level \>70 mg/dL and 186 had Lp(a) level \< 30 mg/dL. To reduce the effect of bias and potential confounding in this observational study, investigators performed rigorous adjustment for the differences in baseline characteristics using propensity-score matching. The propensity-score matched pairs were created by matching patients with Lp(a) \>70 mg/dL and those with Lp(a) \< 30 mg/dL in a 1:1 ratio. The primary cohort comprised 182 propensity-score matched pairs. The primary objective is to test the hypothesis that, compared with patients with Lp(a) \< 30 mg/dL, those with Lp(a) \>70 mg/dL have a faster progression of AVS in a propensity-matched cohort of patients with mild to moderate AVS. Investigators also try to evaluate interactions between Lp(a) groups and baseline clinical and echocardiographic variables for progression of AVS.

Eligibility criteria: Inclusion Criteria:

* Mild to moderate degenerative AVS Aortic peak velocity greater than 2 m/s and smaller than 4 m/s
* LP(a) \>70 mg/dL or \<30 mg/dL
* Patients must provide written informed consent

Exclusion Criteria:

* Bicuspid AVS
* Rheumatic AVS
* Marked bradycardia, tachycardia or 2nd or 3rd degree AV block
* LV ejection fraction \< 40%
* Hypertrophic or restrictive cardiomyopathy

Primary outcomes:
measure: Annualized change in peak aortic jet velocity
timeFrame: From enrollment to the registry to performance of the last follow-up echocardiographic examination, assessed up to 36 months
Secondary outcomes:
measure: Annualized change in mean transvalvular gradient
timeFrame: From enrollment to the registry to performance of the last follow-up echocardiographic examination, assessed up to 36 months
measure: Occurrence of the composite of cardiovascular events (progression to severe aortic stenosis, aortic valve replacement, or cardiovascular mortality)
timeFrame: From enrollment to the registry to performance of the last follow-up echocardiographic examination, assessed up to 36 months
measure: Occurrence of all-cause mortality
timeFrame: From enrollment to the registry to performance of the last follow-up echocardiographic examination, assessed up to 36 months
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Asan Medical Center
name: Duk-Hyun Kang, MD. PhD.
role: PRINCIPAL_INVESTIGATOR
References: