Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial
Steg, P. G.; Szarek, M.; Bhatt, D. L.; Bittner, V. A.; Bregeault, M. F.; Dalby, A. J.; Diaz, R.; Edelberg, J. M.; Goodman, S. G.; Hanotin, C.; Harrington, R. A.; Jukema, J. W.; Lecorps, G.; Mahaffey, K. W.; Moryusef, A.; Ostadal, P.; Parkhomenko, A.; Pordy, R.; Roe, M. T.; Tricoci, P.; Vogel, R.; White, H. D.; Zeiher, A. M.; Schwartz, G. G.; Iñiguez Romo, Andres; González Juanatey, José Ramón; González Juanatey, Carlos
Identifiers
Identifiers
Corporate author
ODYSSEY OUTCOMES Committees and InvestigatorsDate issued
2019Journal title
Circulation
Type of content
Artigo
DeCS
resultado del tratamiento | estudios de seguimiento | farmacoterapia | mediana edad | inyecciones | anticuerpos | método con doble ocultación | síndrome coronario agudo | anciano | hipercolesterolemia | humanos | inhibidores de las hidroximetilglutaril-CoA reductasas | colesterolMeSH
Injections | Hypercholesterolemia | Drug Therapy | Middle Aged | Humans | Antibodies | Treatment Outcome | Cholesterol | Hydroxymethylglutaryl-CoA Reductase Inhibitors | Follow-Up Studies | Acute Coronary Syndrome | Aged | Double-Blind MethodAbstract
BACKGROUND: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. METHODS: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. RESULTS: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for >/=3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths ( P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events ( P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C >/=100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined with achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). CONCLUSIONS: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for >/=3 years, if baseline LDL-C is >/=100 mg/dL, or if achieved LDL-C is low. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01663402.