| Contributors: |
G. G., Schwartz; M., Szarek; V. A., Bittner; D. L., Bhatt; R., Diaz; S. G., Goodman; J. W., Jukema; M., Loy; G., Manvelian; R., Pordy; H. D., White; ODYSSEY OUTCOMES Committees and Investigators: Gregory G Schwartz, Steg P. G.; Gabriel Steg, Philippe; L Bhatt, Deepak; A Bittner, Vera; Diaz, Rafael; G Goodman, Shaun; A Harrington, Robert; Wouter Jukema, J; Szarek, Michael; D White, Harvey; M Zeiher, Andrea; Tricoci, Pierluigi; T Roe, Matthew; W Mahaffey, Kenneth; M Edelberg, Jay; Hanotin, Corinne; Lecorps, Guillaume; Moryusef, Angèle; Pordy, Robert; J Sasiela, William; Tamby, Jean-Françoi; E Aylward, Philip; Drexel, Heinz; Sinnaeve, Peter; Dilic, Mirza; D Lopes, Renato; N Gotcheva, Nina; Prieto, Juan-Carlo; Yong, Huo; López-Jaramillo, Patricio; Pećin, Ivan; Reiner, Zeljko; Ostadal, Petr; Viigimaa, Margu; S Nieminen, Markku; Chumburidze, Vakhtang; Marx, Nikolau; Danchin, Nicola; Liberopoulos, Evangelo; Carlos Montenegro Valdovinos, Pablo; Tse, Hung-Fat; Gabor Kiss, Robert; Xavier, Deni; Zahger, Doron; Valgimigli, Marco; Kimura, Takeshi; Soo Kim, Hyo; Kim, Sang-Hyun; Erglis, Andrej; Laucevicius, Aleksandra; Kedev, Sasko; Yusoff, Khalid; Arturo Ramos López, Gabriel; Alings, Marco; Halvorsen, Sigrun; M Correa Flores, Roger; Budaj, Andrzej; Morais, Joao; Dorobantu, Maria; Karpov, Yuri; D Ristic, Arsen; Chua, Terrance; Murin, Jan; Fras, Zlatko; J Dalby, Anthony; Tuñón, José; Asita de Silva, H; Hagström, Emil; Landmesser, Ulf; Chiang, Chern-En; Sritara, Piyamitr; Guneri, Sema; Parkhomenko, Alexander; K Ray, Kausik; M Moriarty, Patrick; Vogel, Robert; Chaitman, Bernard; F Kelsey, Sheryl; G Olsson, Ander; Rouleau, Jean-Lucien; L Simoons, Maarten; Alexander, Karen; Meloni, Chiara; Rosenson, Robert; G Sijbrands, Eric J; H Alexander, John; Armaganijan, Luciana; Bagai, Akshay |
| Description: |
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. |