Abstract
Aims The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI.
| Original language | English |
|---|---|
| Pages (from-to) | 2801-2809 |
| Number of pages | 9 |
| Journal | European Heart Journal |
| Volume | 40 |
| Issue number | 33 |
| DOIs | |
| Publication status | Published - 1 Sept 2019 |
| Externally published | Yes |
Keywords
- Alirocumab
- Prevention
- MI types
- Mortality
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In: European Heart Journal, Vol. 40, No. 33, 01.09.2019, p. 2801-2809.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial
AU - White, Harvey D.
AU - Steg, Ph. Gabriel
AU - Szarek, Michael
AU - Bhatt, Deepak L.
AU - Bittner, Vera A.
AU - Diaz, Rafael
AU - Edelberg, Jay M.
AU - Erglis, Andrejs
AU - Goodman, Shaun G.
AU - Hanotin, Corinne
AU - Harrington, Robert A.
AU - Jukema, J. Wouter
AU - Lopes, Renato D.
AU - Mahaffey, Kenneth W.
AU - Moryusef, Angele
AU - Pordy, Robert
AU - Roe, Matthew T.
AU - Sritara, Piyamitr
AU - Tricoci, Pierluigi
AU - Zeiher, Andreas M.
AU - Schwartz, Gregory G.
AU - Aylward, Philip E.
AU - Drexel, Heinz
AU - Sinnaeve, Peter
AU - Dilic, Mirza
AU - Lopes, Renato D.
AU - Gotcheva, Nina N.
AU - Goodman, Shaun G.
AU - Prieto, Juan-Carlos
AU - Yong, Huo
AU - Lopez-Jaramillo, Patricio
AU - Pecin, Ivan
AU - Reiner, Zeljko
AU - Ostadal, Petr
AU - Poulsen, Steen Hvitfeldt
AU - Viigimaa, Margus
AU - Nieminen, Markku S.
AU - Danchin, Nicolas
AU - Chumburidze, Vakhtang
AU - Marx, Nikolaus
AU - Liberopoulos, Evangelos
AU - Montenegro Valdovinos, Pablo Carlos
AU - Tse, Hung-Fat
AU - Kiss, Robert Gabor
AU - Xavier, Denis
AU - Zahger, Doron
AU - Valgimigli, Marco
AU - Kimura, Takeshi
AU - Kim, Hyo Soo
AU - Alings, Marco
N1 - Funding Information: Supported by Sanofi and Regeneron Pharmaceuticals. Funding Information: The authors thank the patients, study coordinators, and investigators who participated in this trial. Sophie K. Rushton-Smith (MedLink Healthcare Communications, London, UK) and Michelle D’Souza (Green Lane Cardiovascular Research Unit, Auckland, New Zealand) provided editorial and secretarial assistance in the preparation of the manuscript (limited to formatting, editing for style, referencing, and figure and table editing and submission) and were funded by Fondation Assistance Publique – Hôpitaux de Paris, Paris, France and The Green Lane Research and Educational Fund, Auckland City Hospital, Auckland, New Zealand, respectively. Supported by Sanofi and Regeneron Pharmaceuticals. H.D.W.: receiving grant support paid to the institution and fees for serving on a steering committee for the ODYSSEY Trial from Sanofi-Aventis and Regeneron Pharmaceutical, for the ACCELERATE study from Eli Lilly, for the STRENGTH Trial from Omthera Pharmaceuticals, for the SPIRE Trial from Pfizer USA, for the HEART-FID Study from American Regent; for the CAMELIA Study from Eisai Inc., for the DalGenE Study from DalCor Pharma UK Inc. for the AEGIS-II study from CSL Behring, for the SCORED and SOLOIST Trials from Sanofi-Aventis Australia Pty Ltd, and for the CLEAROUT Study from Esperion Therapeutics Inc. P.G.S.: receiving grant support and fees for serving on a steering committee from Bayer, grant support and lecture fees from Merck, grant support, fees for serving as co-chair of the ODYSSEY OUTCOMES trial and the SCORED trial, consulting fees, and lecture fees from Sanofi, grant support and fees for serving as chair of the CLARIFY registry from Servier, grant support, consulting fees, and fees for serving on an executive steering committee from Amarin, consulting fees and lecture fees from Amgen, consulting fees, lecture fees, and fees for critical-event committee work from Bristol-Myers Squibb, fees for serving on an executive steering committee from Boehringer Ingelheim, fees for critical-event committee work from Pfizer, consulting fees and fees for serving on an executive steering committee from Novartis, consulting fees from Regeneron and Lilly, consulting fees and fees for serving as cochair of the THEMIS trial, and holding a patent (14/657192) on a method for reducing cardiovascular risk. M.S.: receiving consulting fees from CiVi and Esperion, and grant support, consulting fees, and fees for serving on a data and safety monitoring board from Resverlogix and Baxter. D.L.B.: discloses the following relationships—Advisory Board: Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, St. Jude Medical (now Abbott), Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Fractyl, Merck, Novo Nordisk, PLx Pharma, Takeda. V.A.B.: serving on a steering committee for Eli Lilly, serving as the national coordinator of the STRENGTH trial and the site principal investigator for the Artemis trial for AstraZeneca, serving as national coordinator of the Dalgene trial for DalCor, serving as national coordinator of the CLEAR trial for Esperion, serving as a site principal investigator for the COMPASS trial for Bayer, serving as an investigator for Amgen, and receiving advisory board fees from Sanofi. R.D.: receiving grant support from DalCor and TIMI Group, provision of antihypertensive therapy by LEPETIT, fees for serving as a former committee member from ASTRA and Eli Lilly, and receiving grant support and fees for serving as a former committee member from Amgen. J.M.E. (former employee), C.H., and A.M.: employees of Sanofi. A.E: consulting fees and honoraria from Abbott Vascular, Biosensors, Biotronik, Boston Scientific, and Johnson & Johnson/Cordis. S.G.G.: receiving grant support, lecture fees, consulting fees, and advisory board fees from Sanofi, honoraria from Regeneron, grant support, fees for serving on a steering committee, lecture fees, consulting fees, and advisory board fees from Amgen and Lilly, grant support, lecture fees, consulting fees, and advisory board fees from Merck, Pfizer, and AstraZeneca, and fees for serving on a steering committee and for serving as the Canadian national leader for a trial from Esperion. R.A.H.: receiving grant support, paid to his institution, from CSL, Apple, Portola, Janssen, and Novartis, grant support, paid to his institution, from and serving on a data and safety monitoring board for AstraZeneca and Bristol-Myers Squibb, and receiving consulting fees from Amgen, Bayer, Gilead, MyoKardia, and WebMD, and grant support, paid to his institution, and consulting fees from the Medicine Company. J.W.J.: receiving research grants from the Netherlands Heart Foundation, the Interuniversity Cardiology Institute of the Netherlands, the European Community Framework KP7 Program; and other research support from Amgen, Astellas, AstraZeneca, Daiichi Sankyo, Lilly, Merck-Schering-Plough, Pfizer, Roche, and Sanofi-Aventis. R.D.L: receiving research support from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer; consulting fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Medtronic, Merck, Pfizer, and Portola. K.W.M.: receiving consulting fees from Ablynx, Baim Institute, Boehringer Ingelheim, Bristol-Myers Squibb, Cardiometabolic Health Congress, Elsevier, GlaxoSmithKline, Medergy, Medscape, Mitsubishi, Myokardia, Oculeve, Portola, Radiometer, Springer Publishing, Theravance, and WebMD; grant support and consulting fees from AstraZeneca, Johnson & Johnson, Merck, and Novartis, equity in BioPrint Fitness, and grant support from Afferent, Amgen, Apple, Cardiva Medical, Daiichi, Ferring, Google (Verily), Luitpold, Medtronic, and Tenax. R.P.: employee of and shareholder in Regeneron Pharmaceuticals, Inc. M.T.R.: receiving grant support, paid to his institution, from Sanofi Aventis, Ferring Pharmaceuticals, and Myokardia, consulting fees from Janssen Pharmaceuticals, AstraZeneca, Amgen, Ardea Biosciences, and Flatiron, consulting fees and fees for serving on a data and safety monitoring board from Regeneron Pharmaceuticals, fees for serving on a data and safety monitoring board from Roche-Genentech, fees for clinical events adjudication from Eli Lilly, and fees for serving as chairman of the clinical event adjudication committee from Novo Nordisk. P.S.: none declared. P.T.: being employed by and receiving grant support from CSL Behring and grant support from Merck. A.M.Z.: receiving lecture fees from Sanofi, Amgen, Boehringer Ingelheim, and Bayer Healthcare, and advisory board fees and lecture fees from Novartis and Pfizer. G.G.S.: research grants to University of Colorado from Resverlogix, Sanofi, and Roche. Co-inventor of pending US patent application 14/657192 ‘Methods of Reducing Cardiovascular Risk’ assigned in full to University of Colorado. No other potential conflict of interest relevant to this article was reported. Funding Information: The authors thank the patients, study coordinators, and investigators who participated in this trial. Sophie K. Rushton-Smith (MedLink Healthcare Communications, London, UK) and Michelle D’Souza (Green Lane Cardiovascular Research Unit, Auckland, New Zealand) provided editorial and secretarial assistance in the preparation of the manuscript (limited to formatting, editing for style, referencing, and figure and table editing and submission) and were funded by Fondation Assistance Publique – Hôpitaux de Paris, Paris, France and The Green Lane Research and Educational Fund, Auckland City Hospital, Auckland, New Zealand, respectively. Publisher Copyright: © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Aims The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI.
AB - Aims The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI.
KW - Alirocumab
KW - Prevention
KW - MI types
KW - Mortality
UR - http://www.scopus.com/inward/record.url?scp=85070265173&partnerID=8YFLogxK
U2 - 10.1093/eurheartj/ehz299
DO - 10.1093/eurheartj/ehz299
M3 - Article
C2 - 31121022
SN - 0195-668X
VL - 40
SP - 2801
EP - 2809
JO - European Heart Journal
JF - European Heart Journal
IS - 33
ER -