Individualized Dose-Response to Statins Associated with Cardiovascular Disease Outcomes.
JACC Adv
; 3(4)2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38737008
ABSTRACT
Background:
Statins reduce low-density lipoprotein cholesterol (LDL-C) and are efficacious in the prevention of atherosclerotic cardiovascular disease (ASCVD). Dose-response to statins varies among patients and can be modeled using three distinct pharmacological properties (1) E0 (baseline LDL-C), (2) ED50 (potency median dose achieving 50% reduction in LDL-C); and (3) Emax (efficacy maximum LDL-C reduction). However, individualized dose-response and its association with ASCVD events remains unknown.Objective:
We analyze the relationship between ED50 and Emax with real-world cardiovascular disease outcomes.Method:
We leveraged de-identified electronic health record data to identify individuals exposed to multiple doses of the three most commonly prescribed statins (atorvastatin, simvastatin, or rosuvastatin) within the context of their longitudinal healthcare. We derived ED50 and Emax to quantify the relationship with a composite outcome of ASCVD events and all-cause mortality.Results:
We estimated ED50 and Emax for 3,033 unique individuals (atorvastatin 1,632, simvastatin 1,089, and rosuvastatin 312) using a nonlinear, mixed effects dose-response model. Time-to-event analyses revealed that ED50 and Emax are independently associated with the primary endpoint. Hazard ratios were 0.85 (p < 0.01), 0.83 (p < 0.01), and 0.87 (p = 0.10) for ED50 and 1.13 (p < 0.001), 1.06 (p < 0.001), and 1.15 (p = 0.009) for Emax in the atorvastatin, simvastatin, and rosuvastatin cohorts, respectively.Conclusion:
The class-wide association of ED50 and Emax with clinical outcomes indicates that these measures influence the risk for ASCVD events in patients on statins.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article