1. Apabetalone lowers serum alkaline phosphatase and improves cardiovascular risk in patients with cardiovascular disease
- Author
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Gregory G. Schwartz, Kenneth Lebioda, Srinivasan Beddhu, Jan O. Johansson, Christopher Halliday, Mathias Haarhaus, Kamyar Kalantar-Zadeh, Kausik K. Ray, Ewelina Kulikowski, Stephen J. Nicholls, Carmine Zoccali, Vincent Brandenburg, Marcello Tonelli, Norman C.W. Wong, and Michael O. Sweeney
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Time Factors ,Major adverse cardiovascular event ,Down-Regulation ,Comorbidity ,030204 cardiovascular system & hematology ,Lower risk ,Risk Assessment ,03 medical and health sciences ,Clinical Trials, Phase II as Topic ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Alkaline phosphatase ,Humans ,Medicine ,Myocardial infarction ,Risk factor ,1102 Cardiorespiratory Medicine and Haematology ,Aged ,Quinazolinones ,apabetalone ,Dose-Response Relationship, Drug ,business.industry ,Hazard ratio ,Epigenetic ,1103 Clinical Sciences ,Middle Aged ,medicine.disease ,Residual risk ,Treatment Outcome ,030104 developmental biology ,Cardiovascular System & Hematology ,Cardiovascular Diseases ,Residual cardiovascular risk ,Cardiology ,Female ,Liver function ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Mace ,Kidney disease - Abstract
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
- Published
- 2019