TY - JOUR
T1 - Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial
AU - Moriarty, Patrick M.
AU - Thompson, Paul D.
AU - Cannon, Christopher P.
AU - Guyton, John R.
AU - Bergeron, Jean
AU - Zieve, Franklin J.
AU - Bruckert, Eric
AU - Jacobson, Terry A.
AU - Kopecky, Stephen L.
AU - Baccara-Dinet, Marie T.
AU - Du, Yunling
AU - Pordy, Robert
AU - Gipe, Daniel A.
AU - AUTHOR GROUP
AU - Drexel, Heinz
AU - Kaser, Susanne
AU - Toplak, Hermann
AU - Baass, Alexis
AU - Gaudet, Daniel
AU - Farnier, Michel
AU - Krempf, Michel
AU - Moulin, Philippe
AU - Serusclat, Pierre
AU - Cohen, Hofit
AU - Gavish, Dov
AU - Hussein, Osama
AU - Maislos, Maximo
AU - Schurr, Daniel
AU - Arca, Marcello
AU - Averna, Maurizio
AU - Pozzi, Claudio
AU - Balsamo, Cinisello
AU - Heggen, Eli
AU - Langslet, Gisle
AU - Al-Bahrani, Ali
AU - Blagden, Mark
AU - O'Kane, Maurice
AU - Reynolds, Tim
AU - Viljoen, Adie
AU - Andersen, James
AU - Awasty, Vivek
AU - Bayron, Carlos
AU - Bestermann, William
AU - Bolster, Eric
AU - deGoma, Emil
AU - Dunn, Fredrick
AU - Duprez, Daniel
AU - Elam, Marshall
AU - El Shahawy, Mahfouz
AU - Faillace, Robert
AU - Kastelein, John J. P.
PY - 2015
Y1 - 2015
N2 - BACKGROUND: Statin intolerance limits many patients from achieving optimal low-density lipoprotein cholesterol (LDL-C) concentrations. Current options for such patients include using a lower but tolerated dose of a statin and adding or switching to ezetimibe or other non-statin therapies. METHODS: ODYSSEY ALTERNATIVE (NCT01709513) compared alirocumab with ezetimibe in patients at moderate to high cardiovascular risk with statin intolerance (unable to tolerate >= 2 statins, including one at the lowest approved starting dose) due to muscle symptoms. A placebo run-in and statin rechallenge arm were included in an attempt to confirm intolerance. Patients (n = 361) received single-blind subcutaneous (SC) and oral placebo for 4 weeks during placebo run-in. Patients reporting muscle-related symptoms during the run-in were to be withdrawn. Continuing patients were randomized (2:2:1) to double-blind alirocumab 75 mg SC every 2 weeks (Q2W; plus oral placebo), ezetimibe 10 mg/d (plus SC placebo Q2W), or atorvastatin 20 mg/d (rechallenge; plus SC placebo Q2W) for 24 weeks. Alirocumab dose was increased to 150 mg Q2W at week 12 depending on week 8 LDL-C values. Primary end point was percent change in LDL-C from baseline to week 24 (intent-to-treat) for alirocumab vs ezetimibe. RESULTS: Baseline mean (standard deviation) LDL-C was 191.3 (69.3) mg/dL (5.0 [1.8] mmol/L). Alirocumab reduced mean (standard error) LDL-C by 45.0% (2.2%) vs 14.6% (2.2%) with ezetimibe (mean difference 30.4% [3.1%], P <.0001). Skeletal muscle-related events were less frequent with alirocumab vs atorvastatin (hazard ratio 0.61, 95% confidence interval 0.38-0.99, P = .042). CONCLUSIONS: Alirocumab produced greater LDL-C reductions than ezetimibe in statin-intolerant patients, with fewer skeletal-muscle adverse events vs atorvastatin. (C) 2015 National Lipid Association. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
AB - BACKGROUND: Statin intolerance limits many patients from achieving optimal low-density lipoprotein cholesterol (LDL-C) concentrations. Current options for such patients include using a lower but tolerated dose of a statin and adding or switching to ezetimibe or other non-statin therapies. METHODS: ODYSSEY ALTERNATIVE (NCT01709513) compared alirocumab with ezetimibe in patients at moderate to high cardiovascular risk with statin intolerance (unable to tolerate >= 2 statins, including one at the lowest approved starting dose) due to muscle symptoms. A placebo run-in and statin rechallenge arm were included in an attempt to confirm intolerance. Patients (n = 361) received single-blind subcutaneous (SC) and oral placebo for 4 weeks during placebo run-in. Patients reporting muscle-related symptoms during the run-in were to be withdrawn. Continuing patients were randomized (2:2:1) to double-blind alirocumab 75 mg SC every 2 weeks (Q2W; plus oral placebo), ezetimibe 10 mg/d (plus SC placebo Q2W), or atorvastatin 20 mg/d (rechallenge; plus SC placebo Q2W) for 24 weeks. Alirocumab dose was increased to 150 mg Q2W at week 12 depending on week 8 LDL-C values. Primary end point was percent change in LDL-C from baseline to week 24 (intent-to-treat) for alirocumab vs ezetimibe. RESULTS: Baseline mean (standard deviation) LDL-C was 191.3 (69.3) mg/dL (5.0 [1.8] mmol/L). Alirocumab reduced mean (standard error) LDL-C by 45.0% (2.2%) vs 14.6% (2.2%) with ezetimibe (mean difference 30.4% [3.1%], P <.0001). Skeletal muscle-related events were less frequent with alirocumab vs atorvastatin (hazard ratio 0.61, 95% confidence interval 0.38-0.99, P = .042). CONCLUSIONS: Alirocumab produced greater LDL-C reductions than ezetimibe in statin-intolerant patients, with fewer skeletal-muscle adverse events vs atorvastatin. (C) 2015 National Lipid Association. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
U2 - https://doi.org/10.1016/j.jacl.2015.08.006
DO - https://doi.org/10.1016/j.jacl.2015.08.006
M3 - Article
C2 - 26687696
SN - 1933-2874
VL - 9
SP - 758
EP - 769
JO - Journal of clinical lipidology
JF - Journal of clinical lipidology
IS - 6
ER -