Ulf Landmesser1, Jennifer McGinniss2, Ph. Gabriel Steg3,4, Deepak L. Bhatt5, Vera A. Bittner6, Rafael Diaz7, Mirza Dilic8, Shaun G. Goodman9,10, J. Wouter Jukema11,12, Megan Loy13, Ivan Pećin14, Robert Pordy15, Steen H. Poulsen16, Michael Szarek17,18, Harvey D. White19, Gregory G. Schwartz20, for the ODYSSEY OUTCOMES Investigators.
Background and Objectives:
- The 2019 ESC/EAS dyslipidemia guidelines lowered LDL-C treatment goals:
- In patients considered at very high risk (including those with ACS), LDL-C goal of <1.4 mmol/L is recommended together with >50% LDL-C reduction and a lower goal of <1.0 mmol/L may be considered for those with recurrent CV events within 2 years
- This analysis, using the data of ODYSSEY OUTCOMES trial:
- Examined how many patients not at goal with high-intensity or MTD statin treatment achieved new LDL-C treatment goals with alirocumab, according to baseline LDL-C values
- Projected how many would have achieved the new treatment goals with the use of ezetimibe when added to MTD statin therapy
- This sub analysis of the ODYSSEY OUTCOMES trial (multicentre, double-blind, randomized placebo-controlled trial in 18,924 patients of ≥40 years of age, hospitalized with an ACS 1–12 months before randomization) comprised of 17,589 patients with LDL-C ≥1.4 mmol/L at baseline who did not receive ezetimibe treatment
- 94.6% of patients receiving alirocumab achieved LDL-C goal <1.4 mmol/L at ≥1 post-baseline measurement vs. 17.3% patients receiving placebo
- 85.2% of patients with recurrent CV events vs 3.5% receiving placebo, can achieve the lower goal (<1.0 mmol/L)
- In contrast, addition of ezetimibe to optimized statin therapy was projected to achieve LDL-C <1.4 mmol/L in only 10.6% of patients at baseline
- Although the statin/ezetimibe combination is more cost effective than the statin/PCSK9i combination, a substantial number of patients will not achieve the LDL-C goal with this combination
In post ACS patients with residual dyslipidemia despite intensive or MTD statin, adding alirocumab treatment which has been shown to further reduce the risk of MACE and is associated with a reduction in all-cause mortality after ACS, enabled majority of the patients to reach the 2019 ESC guideline targets for LDL-C <1.4 mmol/L (<55 mg/dL) and <1.0 mmol/L (<40 mg/dL) compared to placebo or ezetimibe
ACS, acute coronary syndrome; CV, cardiovascular; EAS, European Atherosclerosis Society; European society of cardiology; ESC, LDL-C, low-density lipoprotein cholesterol; MACE, major adverse cardiac events; MTD, maximum tolerated dose; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor.
- Department of Cardiology, Charite Universitätsmedizin Berlin, Berlin, Germany.
- Regeneron Pharmaceuticals, Tarrytown, NJ, USA.
- Université de Paris, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, FACT (French Alliance for Cardiovascular Trials), INSERM U1148, Paris, France.
- National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, UK.
- Department of Medicine, Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
- University of Alabama at Birmingham, Birmingham, AL, USA.
- Estudios Clínicos Latino América, Instituto Cardiovascular de Rosario, Rosario, Argentina.
- University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina.
- Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.
- St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
- Leiden University Medical Center, Leiden, the Netherlands.
- Netherlands Heart Institute, Utrecht, the Netherlands.
- Sanofi, New Jersey, USA.
- University of Zagreb, Zagreb School of Medicine, University Hospital Center Zagreb, Zagreb, Croatia.
- Regeneron Pharmaceuticals, Tarrytown, NY, USA.
- Aarhus Universitetshospital Skejby, Aarhus N, Denmark.
- State University of New York, Downstate School of Public Health, Brooklyn, NY, USA.
- CPC Clinical Research and Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA.
- Green Lane Cardiovascular Services Auckland City Hospital, Auckland, New Zealand.
- University of Colorado School of Medicine, Aurora, CO, USA.