PMID- 32756916 OWN - NLM STAT- MEDLINE DCOM- 20210202 LR - 20210806 IS - 2380-6591 (Electronic) IS - 2380-6583 (Print) VI - 5 IP - 11 DP - 2020 Nov 1 TI - Clinical Application of High-Sensitivity Troponin Testing in the Atherosclerotic Cardiovascular Disease Framework of the Current Cholesterol Guidelines. PG - 1255-1262 LID - 10.1001/jamacardio.2020.2981 [doi] AB - IMPORTANCE: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol management guidelines identified 2 distinct groups of patients with atherosclerotic cardiovascular disease (ASCVD) prompting different treatment recommendations. OBJECTIVE: To investigate whether the addition of high-sensitivity troponin (hsTn) testing to guideline-derived ASCVD risk can improve risk classification and downstream treatment recommendations. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort biomarker substudy was performed that included 8635 patients enrolled in the Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54) trial. Patients were assigned to risk groups of either very high-risk ASCVD or lower-risk ASCVD based on their cardiovascular history and comorbidities, in line with the 2018 AHA/ACC cholesterol management guidelines criteria. Patients were also classified on the basis of hsTnI level (ARCHITECT assay; Abbott) using cut points of 2 ng/L (limit of detection) and 6 ng/L (risk threshold), followed by joint classification on the basis of clinical features and hsTnI level. The setting was a nested prospective cohort study in a completed multinational trial. Participants were all patients who had a myocardial infarction 1 to 3 years before enrollment, were at least 50 years of age, and had at least 1 high-risk feature. The study dates were October 2010 to December 2014. The dates of analysis were June 2019 to January 2020. MAIN OUTCOMES AND MEASURES: The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. RESULTS: Among 8635 patients enrolled in the PEGASUS-TIMI 54 trial, the median age was 65 years (interquartile range, 58-71 years), and 6614 (76.6%) were men; 8340 (96.6%) were White individuals and 176 (2.0%) were Black individuals. Patients meeting clinical criteria for the very high-risk ASCVD group had a primary end point 3-year event rate of 8.8% compared with 5.0% in the lower-risk ASCVD group (hazard ratio, 2.01; 95% CI, 1.58-2.57; P < .001). When patients in the very high-risk ASCVD group were further risk stratified by hsTnI level, 614 of 6789 patients (9.0%) with an undetectable hsTnI level had a 3-year event rate of 2.7% (<1% per year), which was less than the overall rate in the lower-risk ASCVD group. Analogously, in the lower-risk ASCVD group, 417 of 1846 patients (22.6%) with an hsTnI level exceeding 6 ng/L had an event rate of 9.1%, comparable to the overall rate in the very high-risk ASCVD group. The addition of hsTnI to guideline-derived ASCVD risk led to a net reclassification index at event rate of 0.15 (95% CI, 0.10-0.21). Overall, use of hsTnI reclassified 1031 of 8635 patients (11.9%) (1 in 11 with very high-risk ASCVD and 1 in 4 with lower-risk ASCVD). CONCLUSIONS AND RELEVANCE: The findings of this cohort substudy suggest that a strategy incorporating hsTn into a guideline-derived ASCVD risk algorithm provides enhanced risk stratification and reclassifies 11.9% of patients into a more appropriate risk group. This application of hsTn testing might be used to optimize the care of patients with ASCVD. FAU - Marston, Nicholas A AU - Marston NA AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Bonaca, Marc P AU - Bonaca MP AD - Colorado Prevention Center (CPC) Clinical Research, Division of Cardiology, Department of Medicine, University of Colorado School of Medicine, Aurora. FAU - Jarolim, Petr AU - Jarolim P AD - Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Goodrich, Erica L AU - Goodrich EL AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Bhatt, Deepak L AU - Bhatt DL AD - Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Steg, Philippe G AU - Steg PG AD - Division of Cardiology, Assistance Publique-Hopitaux de Paris, Universite de Paris, Paris, France. FAU - Cohen, Marc AU - Cohen M AD - Newark Beth Israel Medical Center, Rutgers New Jersey Medical School, Newark. FAU - Storey, Robert F AU - Storey RF AD - Division of Cardiology, The University of Sheffield, Sheffield, United Kingdom. FAU - Johanson, Per AU - Johanson P AD - AstraZeneca R&D, Gothenburg, Sweden. FAU - Wiviott, Stephen D AU - Wiviott SD AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Braunwald, Eugene AU - Braunwald E AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Sabatine, Marc S AU - Sabatine MS AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Morrow, David A AU - Morrow DA AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. LA - eng GR - F32 HL144029/HL/NHLBI NIH HHS/United States GR - K08 HL153950/HL/NHLBI NIH HHS/United States GR - L30 HL143770/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Cardiol JT - JAMA cardiology JID - 101676033 RN - 0 (Biomarkers) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Troponin) RN - 97C5T2UQ7J (Cholesterol) SB - IM CIN - JAMA Cardiol. 2020 Nov 1;5(11):1263-1264. PMID: 32756911 MH - Adult MH - Aged MH - *Algorithms MH - Atherosclerosis/*blood/drug therapy/epidemiology MH - Biomarkers/blood MH - Cholesterol/*blood MH - Female MH - Follow-Up Studies MH - *Guideline Adherence MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use MH - Male MH - Middle Aged MH - Prospective Studies MH - Risk Assessment/*methods MH - Risk Factors MH - Troponin/*blood PMC - PMC7407328 COIS- Conflict of Interest Disclosures: Dr Marston reported receiving grant support from the National Institutes of Health. Dr Bonaca reported receiving grant support and consulting fees from Amgen, AstraZeneca, Bayer, and Sanofi. Dr Jarolim reported receiving research support through his institution from Abbott Laboratories, Amgen, AstraZeneca, Daiichi Sankyo, GlaxoSmithKline, LP, Merck, Roche, Takeda, and Waters and receiving consulting fees from Roche. Ms Goodrich reported receiving grants from AstraZeneca and being a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women's Hospital from Abbott Laboratories, Amgen, Aralez, AstraZeneca, Bayer, BRAHMS, Daiichi Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen, MedImmune, Merck, Novartis, Pfizer, Poxel, Quark Pharmaceuticals, Roche, Takeda, The Medicines Company, and Zora Biosciences. Dr Bhatt reported receiving grants from Abbott Laboratories, Afimmune, Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories/AstraZeneca, Fractyl, Icahn School of Medicine at Mount Sinai, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Synaptic, and The Medicines Company; receiving personal fees from the American College of Cardiology, Bayer, Belvoir Publications, Cleveland Clinic, CSL Behring, Duke Clinical Research Institute, Elsevier, Ferring Pharmaceuticals, Journal of the American College of Cardiology, Level Ex, Mayo Clinic, Medtelligence/ReachMD, MJH Life Sciences, Population Health Research Institute, Slack Publications, TobeSoft, and WebMD; and receiving personal fees and/or nonfinancial support from the American Heart Association, Boehringer Ingelheim, Harvard Clinical Research Institute (now Baim Institute for Clinical Research), HMP Global, and Society of Cardiovascular Patient Care. Dr Steg reported receiving research grants from Amarin, Bayer, Sanofi, and Servier and receiving speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer/Janssen, Boehringer Ingelheim, Bristol-Myers Squibb, Idorsia, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi, and Servier. Dr Cohen reported receiving honoraria for serving on speakers' bureaus and advisory boards for AstraZeneca. Dr Storey reported receiving research grants, consultancy fees, and honoraria from AstraZeneca, Bayer, and Bristol-Myers Squibb/Pfizer; receiving research grants and consultancy fees from GlyCardial Diagnostics and Thromboserin; receiving consultancy fees from Amgen, Haemonetics, and Portola; and receiving honoraria from Medscape. Dr Wiviott reported receiving grants from Amgen, Arena, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eisai, Eli Lilly, Janssen, Merck, and Sanofi; receiving consulting fees from Aegerion, Allergan, AngelMed, Arena, AstraZeneca, Boehringer Ingelheim, Boston Clinical Research Institute, Bristol-Myers Squibb, Daiichi Sankyo, Eisai, Eli Lilly, Icon Clinical, Janssen, Lexicon, Merck, Servier, St Jude Medical, and XOMA; and being a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women's Hospital from Abbott Laboratories, Amgen, Aralez, AstraZeneca, Bayer, BRAHMS, Daiichi Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen, MedImmune, Merck, Novartis, Pfizer, Poxel, Quark Pharmaceuticals, Roche, Takeda, The Medicines Company, and Zora Biosciences. Dr Braunwald reported receiving grants from AstraZeneca, Daiichi Sankyo, Merck, and Novartis and receiving personal fees from Amgen, Cardurion, MyoKardia, Novo Nordisk, and Verve. Dr Sabatine reported receiving research grant support through Brigham and Women's Hospital from Amgen, AstraZeneca, Bayer, Daiichi Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen, MedImmune, Merck, Novartis, Pfizer, Poxel, Quark Pharmaceuticals, Takeda, and The Medicines Company and receiving consulting fees from Amgen, Anthos Therapeutics, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, DalCor, Dyrnamix, Esperion, IFM Therapeutics, Intarcia, Ionis, Janssen, MedImmune, Merck, Novartis, and The Medicines Company. Dr Sabatine reported being a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women's Hospital from Abbott Laboratories, Aralez, Roche, and Zora Biosciences. Dr Morrow reported receiving grants to Brigham and Women's Hospital from Abbott Laboratories, AstraZeneca, BRAHMS, Daiichi Sankyo, Eisai, GlaxoSmithKline, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Roche, Takeda, The Medicines Company, and Zora Biosciences and receiving consulting fees from Aralez, AstraZeneca, Bayer, InCarda, Novartis, and Roche. No other disclosures were reported. EDAT- 2020/08/07 06:00 MHDA- 2021/02/03 06:00 PMCR- 2021/08/05 CRDT- 2020/08/07 06:00 PHST- 2020/08/07 06:00 [pubmed] PHST- 2021/02/03 06:00 [medline] PHST- 2020/08/07 06:00 [entrez] PHST- 2021/08/05 00:00 [pmc-release] AID - 2768907 [pii] AID - hoi200052 [pii] AID - 10.1001/jamacardio.2020.2981 [doi] PST - ppublish SO - JAMA Cardiol. 2020 Nov 1;5(11):1255-1262. doi: 10.1001/jamacardio.2020.2981.