Naslov
Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment

Autori
Schwartz, Gregory G. ; Szarek, Michael ; Bittner, Vera A. ; Bhatt, Deepak L. ; Diaz, Rafael ; Goodman, Shaun G. ; Jukema, J. Wouter ; Loy, Megan ; Manvelian, Garen ; Pordy, Robert ; White, Harvey D. ; Steg, Philippe Gabriel ; ODYSSEY OUTCOMES Committees and Investigators ; (Lukenda, Josip ; et al.)

Kolaboracija
ODYSSEY OUTCOMES Committees and Investigators

Izvornik
Diabetes Care (0149-5992) 44 (2021), 5; 1219-1227

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Antibodies, Monoclonal, Humanized Anticholesteremic Agents* Diabetes Mellitus, Type 2* / drug therapy Diabetes Mellitus, Type 2* / epidemiology Double-Blind Method Humans Lipoprotein(a) Proprotein Convertase 9 Treatment Outcome

Sažetak
Objective: In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor. Research design and methods: In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data. Results: Among 13, 480 patients without diabetes at baseline, 1, 324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02-1.06, P < 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85-1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment-baseline lipoprotein(a) interaction P = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03-1.12 ; P = 0.0002) for incident type 2 diabetes. Conclusions: In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment- related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined. Trial registration: ClinicalTrials.gov NCT01663402.

Izvorni jezik
Engleski

POVEZANOST RADA