Effect of Alirocumab on Mortality After Acute Coronary Syndromes.

Autor:	Steg PG; Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Université de Paris, FACT (French Alliance for Cardiovascular Trials), INSERM U1148, Paris, France (P.G.S.).; National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, United Kingdom (P.G.S.)., Szarek M; State University of New York, Downstate School of Public Health, Brooklyn (M.S.)., Bhatt DL; Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.)., Bittner VA; Division of Cardiovascular Disease, University of Alabama at Birmingham. (V.A.B.)., Brégeault MF; Sanofi, Paris, France (M.F.B., C.H., G.L.)., Dalby AJ; Milpark Hospital, Johannesburg, Republic of South Africa (A.J.D.)., Diaz R; Estudios Cardiológicos Latinoamérica, Instituto Cardiovascular de Rosario, Argentina (R.D.)., Edelberg JM; Sanofi, Bridgewater, NJ (J.M.E., A.M.)., Goodman SG; Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada and St. Michael's Hospital, University of Toronto, Canada (S.G.G.)., Hanotin C; Sanofi, Paris, France (M.F.B., C.H., G.L.)., Harrington RA; Stanford Center for Clinical Research, Department of Medicine, Stanford University, CA (R.A.H., K.W.M.)., Jukema JW; Department of Cardiology, Leiden University Medical Center, the Netherlands (J.W.J.)., Lecorps G; Sanofi, Paris, France (M.F.B., C.H., G.L.)., Mahaffey KW; Stanford Center for Clinical Research, Department of Medicine, Stanford University, CA (R.A.H., K.W.M.)., Moryusef A; Sanofi, Bridgewater, NJ (J.M.E., A.M.)., Ostadal P; Na Homolce Hospital, Prague, Czech Republic (P.O.)., Parkhomenko A; Institute of Cardiology, Kyiv, Ukraine (A.P.)., Pordy R; Regeneron Pharmaceuticals Inc, Tarrytown, NY (R.P.)., Roe MT; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (M.T.R., P.T.).; Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC (M.T.R.)., Tricoci P; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (M.T.R., P.T.)., Vogel R; University of Colorado Denver (R.V.)., White HD; Green Lane Cardiovascular Services Auckland City Hospital, New Zealand (H.D.W.)., Zeiher AM; Department of Medicine III, Goethe University, Frankfurt am Main, Germany (A.M.Z.)., Schwartz GG; Division of Cardiology, University of Colorado School of Medicine, Aurora (G.G.S.).
Jazyk:	angličtina
Zdroj:	Circulation [Circulation] 2019 Jul 09; Vol. 140 (2), pp. 103-112. Date of Electronic Publication: 2019 May 23.
DOI:	10.1161/CIRCULATIONAHA.118.038840
Abstrakt:	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; P interaction =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.
Databáze:	MEDLINE
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