Apabetalone lowers serum alkaline phosphatase and improves cardiovascular risk in patients with cardiovascular disease.
Aged
Alkaline Phosphatase
/ blood
Biomarkers
/ blood
Cardiovascular Diseases
/ blood
Clinical Trials, Phase II as Topic
Comorbidity
Dose-Response Relationship, Drug
Down-Regulation
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/ therapeutic use
Male
Middle Aged
Quinazolinones
/ adverse effects
Risk Assessment
Risk Factors
Time Factors
Treatment Outcome
Alkaline phosphatase
Epigenetic
Major adverse cardiovascular event
Residual cardiovascular risk
apabetalone
Journal
Atherosclerosis
ISSN: 1879-1484
Titre abrégé: Atherosclerosis
Pays: Ireland
ID NLM: 0242543
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
06
04
2019
revised:
19
08
2019
accepted:
12
09
2019
pubmed:
1
10
2019
medline:
4
8
2020
entrez:
1
10
2019
Statut:
ppublish
Résumé
In patients with cardiovascular disease, considerable residual risk remains despite evidence-based secondary prevention measures. Alkaline phosphatase (ALP) has been suggested as a modifiable cardiovascular risk factor. We sought to determine whether cardiovascular risk reduction by the bromodomain and extra-terminal (BET) protein inhibitor apabetalone is associated with the concomitant lowering of serum ALP. In a post-hoc analysis of 795 patients with established coronary heart disease and statin treatment, who participated in phase 2 placebo-controlled trials of apabetalone, we determined the effect of assigned treatment for up to 24 weeks on the incidence of major adverse cardiovascular events (MACE) and serum ALP. Baseline ALP (median 72 U/L) predicted MACE (death, non-fatal myocardial infarction, coronary revascularization, or hospitalization for cardiovascular causes), independent of high-sensitivity C-reactive protein (hsCRP), sex, age, race, study, cardiovascular risk factors, chronic kidney disease (CKD), liver function markers and treatment allocation (hazard ratio [HR] per standard deviation [SD] 1.6, 95% CI 1.19-2.16, p = 0.002). Mean placebo-corrected decreases in ALP from baseline were 9.2% (p < 0.001) after 12-14 weeks and 7.7% (p < 0.001) after 24-26 weeks of apabetalone treatment. In the apabetalone group, a 1-SD reduction in ALP was associated with a HR for MACE of 0.64 (95% CI 0.46-0.90, p = 0.009). Serum ALP predicts residual cardiovascular risk, independent of hsCRP, established cardiovascular risk factors and CKD, in patients with cardiovascular disease on statin treatment. Apabetalone lowers serum ALP, which was associated with a lower risk of cardiovascular events. Whether the beneficial cardiovascular effects of apabetalone are causally related to ALP reduction remains undetermined.
Sections du résumé
BACKGROUND AND AIMS
In patients with cardiovascular disease, considerable residual risk remains despite evidence-based secondary prevention measures. Alkaline phosphatase (ALP) has been suggested as a modifiable cardiovascular risk factor. We sought to determine whether cardiovascular risk reduction by the bromodomain and extra-terminal (BET) protein inhibitor apabetalone is associated with the concomitant lowering of serum ALP.
METHODS
In a post-hoc analysis of 795 patients with established coronary heart disease and statin treatment, who participated in phase 2 placebo-controlled trials of apabetalone, we determined the effect of assigned treatment for up to 24 weeks on the incidence of major adverse cardiovascular events (MACE) and serum ALP.
RESULTS
Baseline ALP (median 72 U/L) predicted MACE (death, non-fatal myocardial infarction, coronary revascularization, or hospitalization for cardiovascular causes), independent of high-sensitivity C-reactive protein (hsCRP), sex, age, race, study, cardiovascular risk factors, chronic kidney disease (CKD), liver function markers and treatment allocation (hazard ratio [HR] per standard deviation [SD] 1.6, 95% CI 1.19-2.16, p = 0.002). Mean placebo-corrected decreases in ALP from baseline were 9.2% (p < 0.001) after 12-14 weeks and 7.7% (p < 0.001) after 24-26 weeks of apabetalone treatment. In the apabetalone group, a 1-SD reduction in ALP was associated with a HR for MACE of 0.64 (95% CI 0.46-0.90, p = 0.009).
CONCLUSIONS
Serum ALP predicts residual cardiovascular risk, independent of hsCRP, established cardiovascular risk factors and CKD, in patients with cardiovascular disease on statin treatment. Apabetalone lowers serum ALP, which was associated with a lower risk of cardiovascular events. Whether the beneficial cardiovascular effects of apabetalone are causally related to ALP reduction remains undetermined.
Identifiants
pubmed: 31568963
pii: S0021-9150(19)31476-5
doi: 10.1016/j.atherosclerosis.2019.09.002
pii:
doi:
Substances chimiques
Biomarkers
0
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Quinazolinones
0
apabetalone
8R4A7GDZ1D
Alkaline Phosphatase
EC 3.1.3.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
59-65Informations de copyright
Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.