Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab.

Autor:	Hagström E; Uppsala University, Department of Medical Sciences, and Uppsala Clinical Research Center, Sweden (E.H.)., Steg PG; Department of Cardiology, Université de Paris, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, FACT (French Alliance for Cardiovascular Trials), and INSERM U1148, France (P.G.S.).; Imperial College, Royal Brompton Hospital, London, UK (P.G.S.)., Szarek M; CPC Clinical Research (M. Szarek), University of Colorado School of Medicine, Aurora.; Division of Cardiology (M. Szarek, G.G.S.), University of Colorado School of Medicine, Aurora.; State University of New York, Downstate Health Sciences University, Brooklyn (M. Szarek)., Bhatt DL; Department of Medicine, 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.)., Danchin N; Department of Cardiology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France (N.D.).; Université Paris Descartes, France (N.D.)., Diaz R; Estudios Cardiológicos Latino América, Instituto Cardiovascular de Rosario, Argentina (R.D.)., Goodman SG; Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada (S.G.G.).; St. Michael's Hospital, University of Toronto, Ontario, Canada (S.G.G.)., Harrington RA; Stanford Center for Clinical Research, Department of Medicine, Stanford University, CA (R.A.H.)., Jukema JW; Department of Cardiology, Leiden University Medical Center, the Netherlands (J.W.J.).; Netherlands Heart Institute, Utrecht (J.W.J.)., Liberopoulos E; School of Medicine, National and Kapodistrian University of Athens, Greece (E.L.)., Marx N; University Hospital, RWTH Aachen University, Germany (N.M.)., McGinniss J; Regeneron Pharmaceuticals Inc, Tarrytown, NY (J.M., G.M., R.P.)., Manvelian G; Regeneron Pharmaceuticals Inc, Tarrytown, NY (J.M., G.M., R.P.)., Pordy R; Regeneron Pharmaceuticals Inc, Tarrytown, NY (J.M., G.M., R.P.)., Scemama M; Sanofi, Paris, France (M. Scemama)., White HD; Green Lane Cardiovascular Services, Auckland City Hospital and Auckland University, 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 (M. Szarek, G.G.S.), University of Colorado School of Medicine, Aurora.
Jazyk:	angličtina
Zdroj:	Circulation [Circulation] 2022 Aug 30; Vol. 146 (9), pp. 657-672. Date of Electronic Publication: 2022 Jun 30.
DOI:	10.1161/CIRCULATIONAHA.121.057807
Abstrakt:	Background: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. Methods: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score-matched models. Results: Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9-3.6], 4.0 [95% CI, 3.6-4.5], and 5.5 [95% CI, 5.0-6.1] events per 100 patient-years in strata <75, 75-<90, ≥90 mg/dL, respectively; P trend <0.0001) and after adjustment for low-density lipoprotein cholesterol ( P trend =0.035). Higher baseline apoB stratum was associated with greater relative ( P trend <0.0001) and absolute reduction in MACE with alirocumab versus placebo. In the alirocumab group, the incidence of MACE after month 4 decreased monotonically across decreasing achieved apoB strata (4.26 [95% CI, 3.78-4.79], 3.09 [95% CI, 2.69-3.54], and 2.41 [95% CI, 2.11-2.76] events per 100 patient-years in strata ≥50, >35-<50, and ≤35 mg/dL, respectively). Compared with propensity score-matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol but not vice versa. Conclusions: In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as ≤35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome. Registration: URL: https://www. Clinicaltrials: gov; Unique identifier: NCT01663402.
Databáze:	MEDLINE
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