presenting with isolated anterior ST-segment depressions. Circulation 2008; 118: S-654. Abstract 1999.
7 45. Chapman AR, Adamson PD, Mills NL. Assessment and classification of patients with myocardial injury and infarction in clinical practice. Heart 2017; 103:10–18. 0/3-hour hs-troponin protocol: single undetectable hs-troponin is enough to rule out MI if patient presents>2 hours after pain onset.
8 46. Ioannidis JPA, Salem D, Chew PW, et al. Accuracy of imaging technologies in the diagnosis of acute cardiac ischemia in the emergency department: a meta- analysis. Ann Emerg Med 2001; 37: 471–7. + Shiran A, Blondheim DS, Shimoni S, et al. Two-dimensional strain echocardiography for diagnosing chest pain in the emergency room: a multicentre prospective study by the Israeli echo research group. Eur Heart J Cardiovasc Imaging. 2017 Sep 1;18(9):1016-1024
Undetectable hs-troponin and hs-troponin algorithms (+references 28-30 and 45)
1 47. Chapman AR, Hesse K, Andrews J, et al. High-sensitivity cardiac troponin I and clinical risk scores in patients with suspected acute coronary syndrome. Circulation 2018; 138:1654-65. +Also: Modified HEART score and hs-troponin in suspected acute myocardial infarction. JACC 2019; 73: 873
2 48.Chapman AR, Anand A, Boeddinghaus J. Comparison of the efficacy and safety of early rule-out pathways for acute myocardial infarction. Circulation 2017; 135(17):1586–1596. This study validates the 0/3hr delta algorithm of reference 45 and 49, called High STEAS algorithm: negative predictive value 99.5% for MI, 100% for death (4 missed cases, all had detectable troponin with a delta troponin less than cutoff)
3 49. Shah ASV, Anand A, Chapman AR, et al. Measurement of cardiac troponin for exclusion of myocardial infarction—Authors’ reply. Lancet 2016; 387:2289–2291.
4 50. Bandstein N, Ljung R, Johansson M, Holzmann MJ. Undetectable high-sensitivity cardiac troponin T level in the emergency department and risk of myocardial infarction. J Am Coll Cardiol 2014; 63 (23): 2569–2578. Single admission non-detectable hs-troponin+nonischemic ECG → Negative predictive value 99.8% for MI, 100% for death.
5 51. Chapman AR, Lee KK, McAllister DA, et al. Association of high-sensitivity cardiac troponin I concentration with cardiac outcomes in patients with suspected acute coronary syndromes. JAMA 2017; 318(19):1913–1924. (Meta-analysis of undetectable hs-troponin on presentation).
6 52. Pickering JW, Than MP, Cullen L, et al. Rapid rule-out of acute myocardial infarction with a single high-sensitivity cardiac troponin T measurement below the limit of detection: a collaborative meta-analysis. Ann Intern Med 2017; 166(10):715–724.
7 53. Badertscher P, Boeddinghaus J, Twerenbold R, et al. Direct comparison of the 0/1h and 0/3h algorithms for early rule-out of acute myocardial infarction. Circulation 2018; 137:2536–2538: 0/1 hour is superior to old protocol (using MI cutoff). High negative predictive value of 99.8%.
8 54. Sandoval Y, Nowak R, deFellipi CR, et al. Myocardial infarction risk stratification with a single measurement of troponin I. J Am Coll Cardiol 2019; 74:271–282: A single very low hs-troponin I has a 30-day negative predictive value of 99.8% for MI/death, using troponin I US assays (very low defined as <0.005 ng/ml, the detection cutoff being 0.002). It seems <0.005 ng/ml is a good rule-out cutoff in all hs-troponin assays; hs troponin does not have to be undetectable, as assays are becoming more sensitive.
9 55. Twerenbold R., Costabel J.P., Nestelberger T., et al. Outcome of applying the ESC 0/1-hour algorithm in patients with suspected myocardial infarction. J Am Coll Cardiol 2019; 74:483–494. Very low cardiovascular death 0.1% at 30 days in the rule out group.
10 56.Antman EM, Tanasijevic MJ, Thompson B, et al. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med 1996; 201: 335: 1342–9.
11 57. Sabatine M.S., Morrow D.A., de Lemos J.A., et al. Detection of acute changes in circulating troponin in the setting of transient stress test-induced myocardial ischaemia using an ultrasensitive assay: results from TIMI 35. Eur Heart J 2009; 30:162–169.
12 58. Topol EJ, Yadav JS. Recognition of the importance of embolization in atherosclerotic vascular disease. Circulation 2000; 101: 570–80.
13 59. Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006; 355: 2203–16. ACUITY trial.
14 60. Giugliano RP, White JA, Boden C, et al. Early versus delayed, provisional eptifibatide in acute coronary syndromes. N Engl J Med 2009; 360: 2176–90. EARLY ACS trial.
15 61. Mehta SR, Granger CB, Boden WE, et al. Early versus delayed invasive intervention in acute coronary syndromes. N Engl J Med 2009; 360: 2165–75. TIMACS trial.
Invasive strategy vs conservative strategy
1 62. Cannon CP, Weintraub WS, Demopoulos LA, et al. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban (TACTICS-TIMI 18 trial). N Engl J Med 2001; 344: 1879–87.
2 63. Fox KA, Poole-Wilson P, Clayton TC, et al. 5-year outcome of an interventional strategy in non-ST-elevation acute coronary syndrome: the British Heart Foundation RITA 3 randomised trial. Lancet 2005; 366: 914–20.
3 64. Wallentin L, Lagerqvist B, Husted S, et al. Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial. FRISC II Investigators. Lancet 2000; 356: 9–16.
4 65. de Winter RJ, Windhausen F, Cornel JH, et al. Early invasive versus selectively invasive management for acute coronary syndromes. N Engl J Med 2005; 353: 1095–104. ICTUS trial.
Timing of initial invasive strategy
1 66. Kofoed KF, Kelbæk H, Hansen PR, et al. Early Versus Standard Care Invasive Examination and Treatment of Patients with Non-ST-Segment Elevation Acute Coronary Syndrome: The VERDICT Randomized Controlled Trial. Circulation 2018; 138: 2741–2750.
2 67. Lemesle G, Laine M, Pankert M, et al. Optimal timing of intervention in non-ST-segment elevation coronary syndromes without pretreatment with P2Y12-ADP receptor antagonists: the EARLY randomized trial. Presented at AHA 2018, Novemeber 11, 2018, Chicago, IL
3 68. Montalescot G., Cayla G., Collet J. P., Elhadad S., Beygui F., Le Breton H., et al. Immediate vs delayed intervention for acute coronary syndromes: a randomized clinical trial. JAMA 2009; 302, 947–954.
Initial medical therapy
1 69. Schüpke S, Neumann FJ, Menichelli M, et al., on behalf of the ISAR-REACT 5 Trial Investigators. Ticagrelor or Prasugrel in Patients With Acute Coronary Syndromes. N Engl J Med 2019; 381:1524–34.
2 70. Montalescot G, Bolognese L, Dudek D, et al. Pretreatment with prasugrel in non-ST segment elevation myocardial infarction. N Engl J Med 2013; 369: 999–1010. ACCOAST trial.+Also, SCAAR registry: Dworeck C, Redfors B, Angerås O, et al. Association of Pretreatment With P2Y12 Receptor Antagonists Preceding Percutaneous Coronary Intervention in Non-ST-Segment Elevation Acute Coronary Syndromes With Outcomes. JAMA Netw Open. 2020 Oct 1;3(10):e2018735.
3 71. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494–502. CURE trial.
4 72. Hanna EB, Rao SV, Manoukian SV, Saucedo JF. The evolving role of glycoprotein IIb-IIIa inhibitors in the setting of percutaneeous coronary intervention. Strategies to minimize bleeding and improve outcomes. J Am Coll Cardiol 2010; 3: 1209–19.
5 73. Chen ZM, Pan HC, Chen YP, et al. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005; 366: 1622–32. COMMIT-CCS trial.
6 74. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350: 1495.