Original article Herz 2014 DOI 10.1007/s00059-014-4161-7 Received: 17 June 2014 Revised: 25 August 2014 Accepted: 25 September 2014 © Urban & Vogel 2014
U. Zeymer1, 2 · H. Heuer3 · P. Schwimmbeck4 · S. Genth-Zotz5 · K. Wolff6 · C.A. Nienaber7 · The EPICOR Investigators 1 Klinikum Ludwigshafen, Ludwigshafen 2 Institut für Herzinfarktforschung, Ludwigshafen 3 Klinik für Innere Medizin I, St. Johannes-Hospital gGmbH, Dortmund 4 Klinik für Kardiologie, Klinikum Leverkusen, Leverkusen 5 Klinik für Innere Medizin I, Katholisches Klinikum Mainz, Mainz 6 Medizinische Abteilung, AstraZeneca GmbH, Wedel 7 Universitäres Herzzentrum Rostock, Universitätsmedizin Rostock, Rostock
Guideline-adherent therapy in patients with acute coronary syndromes The EPICOR registry in Germany
Despite sustained research efforts and clinical progress, cardiovascular diseases are still among the leading causes for death and morbidity in industrialized countries including Germany [1]. Among these, acute coronary syndrome (ACS) is a highly prevalent manifestation. The spectrum of ACS comprises, based on ECG criteria and troponin measurements, STsegment elevation (STEMI) and nonST-segment elevation myocardial infarction (NSTEMI) as well as unstable angina (UA) [2]. While the spectrum of conditions shares many pathophysiological similarities [3], management differs to a certain extent, reflected in the development of heterogeneous guidelines by the European Society for Cardiology and associated societies [2, 4, 5]. Nonetheless, antithrombotic agents are the mainstay therapy for all manifestations of ACS [6]. In agreement with the importance of ACS, a substantial body of data from observational studies and registries has been collected in projects such as the Global Registry of Acute Coronary Events (GRACE [7, 8]), and various national projects such as the US American Get with the Guidelines registry (GWTG [9]), the Canadian ACS-2 registry [10], the French FAST-MI
2010 registry [11], the Italian IN-ACS Outcome registry [12] or the Swiss AMIS-plus registry [13]. In Germany, ACS registries are partially limited to certain geographic areas such as the MONICA/CORA Myocardial Infarction registry in the Augsburg area [14], the Myocardial Infarction Network Essen [15], the German Heart Centre ACS registry [16], and national efforts such as the German Acute Coronary Syndromes registry (ACOS) [17] or, more recently, the quality control registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte (ALKK) [18]. In recent years, substantial progress has been made in the management of ACS, due to structural improvements (leading to reduced admission times), optimized interventional procedures, and also availability of new antithrombotic agents that are used alone or in combinations [6]. Thus, there is a need for current and representative observational data on utilization and patient outcomes. The EPICOR (Long-Term Follow-Up of Antithrombotic Management Patterns in Acute Coronary Syndrome Patients) was set up to generate a snapshot of such real-life data. In this article, we present the baseline data of the German cohort, with a descriptive
comparison between STEMI and NSTEMI/UA patients with regard to management and in-hospital outcomes. During the course of the study, the NSTEMI-ACS guidelines [2] were updated mid-2011 and the STEMI-ACS ESC guidelines in 2012 [4].
Methods Design EPICOR is a prospective, open, observational, nonrandomized cohort study conducted in 555 centers in 20 countries of four geographic regions (Northern Europe, Southern Europe, Eastern Europe, and Latin America). The recruitment phase was from September 2010 to March 2011, while the follow-up phase of study is on-going; 629 patients were included in Germany. The rationale, design, and aims of the study were described in greater detail recently [19]. In brief, participating centers were selected to achieve a sample of representative patients with ACS receiving antithrombotic management in their respective country. This study was conducted in accordance with the EU Note Herz 2014
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Original article Tab. 1 Demographics, medical history, and comorbidities
STEMI (N=296) n (%)
UA/NSTEMI (N=333) n (%)
Age, years ± SD Gender – Male – Female CV risk factors, any – Hypertension – Hypercholesterolemia – Diabetes mellitus – Family history of CVD – Smoking, current – Smoking, former – Obesity: BMI >30 kg/m2 Previous CVD – Myocardial infarction – Prior PCI – Prior CABG – Chronic angina – Heart failure – Atrial fibrillation – TIA/Stroke – Peripheral vascular disease Previous non-CVD disease, any – Chronic renal failure – COPD or other chronic lung disease – Severe liver disease – Esophageal varices – Major surgerya
58.7±12.0 229 (77.4) 67 (22.6) 248 (83.8) 177 (59.8) 159 (53.7) 48 (16.2) 118 (39.9) 137 (46.3) 62 (20.9) 76 (25.7) 57 (19.3) 20 (6.8) 27 (9.1) 7 (2.4) 9 (3.0) 8 (2.7) 7 (2.4) 10 (3.4) 12 (4.1) 79 (26.7) 9 (3.0) 23 (7.8) 1 (0.3%) 2 (0.7%) 3 (1.0%)
64.3±12.4 258 (77.5) 75 (22.5) 314 (94.3) 265 (79.6) 200 (60.1) 84 (25.2) 117 (35.1) 104 (31.2) 102 (30.6) 108 (32.4) 163 (48.9) 89 (26.7) 105 (31.5) 40 (12.0) 30 (9.0) 26 (7.8) 29 (8.7) 22 (6.6) 33 (9.9) 132 (39.6) 37 (11.1) 30 (9.0) 2 (0.6%) 0 (0.0%) 7 (2.1%)
Total (N=629) n (%) 61.7±12.5 487 (77.4) 142 (22.6) 562 (89.3) 442 (70.3) 359 (57.1) 132 (21.0) 235 (37.4) 241 (38.3) 164 (26.1) 184 (29.3) 220 (35.0) 109 (17.3) 132 (21.0) 47 (7.5) 39 (6.2) 34 (5.4) 36 (5.7) 32 (5.1) 45 (7.2) 211 (33.5) 46 (7.3) 53 (8.4) 3 (0.5%) 2 (0.3%) 10 (1.6%)
BMI body mass index, CABG coronary artery bypass graft, COPD chronic obstructive pulmonary disease, CV cardiovascular, CVD cardiovascular disease, NSTEMI non-ST-segment elevation myocardial infarction, SD standard deviation, STEMI ST-segment elevation myocardial infarction, TIA transient ischemic attack, UA unstable anginaaIn the 6 months prior to the index ACS event. None of the bleeding events was related to a medical/ surgical procedure
for Guidance on Good Clinical Practice CPMP/ECH/135/95, the Declaration of Helsinki revision, and applicable legislation for noninterventional studies. Since only hospital survivors were included, patients gave written informed consent prior to discharge. EPICOR was initiated at the site level only after local and ethics approval requirements had been obtained. Emphasis was placed on consecutive enrolment of patients at each site. The study was planned, steered, and its data interpreted and disseminated by a scientific committee [19] consisting of representatives from each country. The study is registered in ClinicalTrials.gov under the identifier NCT01171404.
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Patients Men and women of 18 years or older were eligible if they met the following criteria: (1) hospitalization within 24 h of onset of symptoms of the index event for the first time, with a final (discharge) diagnosis of STEMI or NSTEMI/UA, (2) written informed consent at the time of hospital discharge, (3) completion of a Contact Order Form, on which they agreed to be contacted by telephone for regular follow-up interviews during the postdischarge phase. Patients were excluded if (1) ACS was precipitated by or was a complication of surgery, trauma, gastrointestinal bleeding, or postpercutaneous coronary intervention (PCI); (2) ACS occurred during hospitalization for other reasons; (3)
any condition/circumstance which, in the opinion of the investigator, could significantly limit the complete follow-up of the patient was present (e.g., tourist, nonnative speaker or other insufficient understanding of the local language; psychiatric disturbances); (4) previous enrolment in the EPICOR study; (5) currently participating in another clinical trial; or (6) presence of serious/severe comorbidities which, in the opinion of the investigator, would limit short-term (i.e., 6-month) life expectancy. ACS definitions were as follows: F STEMI—Chest pain/discomfort and persistent ST-segment elevation (>30 min) of ≥0.1 mV in two or more contiguous ECG leads or presumed new left bundle branch block (LBBB) on admission, and elevation of cardiac biomarkers (CK-MB, troponins) at least one value above the 99th percentile of the upper reference limit. F NSTEMI—Chest pain/discomfort, and lack of persistent ST-segment elevation, LBBB or intraventricular conduction disturbances, and elevation of cardiac biomarkers (CK-MB, troponins) at least one value above the 99th percentile of the upper reference limit. F UA—Symptoms of angina at rest or on minimal exercise, and transient ST-T changes, and no significant increase in biomarkers of necrosis but objective evidence of ischemia by noninvasive imaging or significant coronary stenosis at angiography. Major bleeding events in the 6 months preceding the index event were bleedings that required hospitalization or urgent medical care and/or blood transfusion and/or caused a significant hematocrit drop in the previous 6 months.
Data collection Data were collected in an electronic case report form (eCRF), at baseline (admission to hospital), at discharge from hospital, and at follow-up telephone contacts made by well-trained interviewers (follow-up data not reported here). No onsite monitoring with source data verification was performed.
Abstract · Zusammenfassung Herz 2014 · [jvn]:[afp]–[alp] DOI 10.1007/s00059-014-4161-7 © Urban & Vogel 2014 U. Zeymer · H. Heuer · P. Schwimmbeck · S. Genth-Zotz · K. Wolff · C.A. Nienaber · The EPICOR Investigators
Guideline-adherent therapy in patients with acute coronary syndromes. The EPICOR registry in Germany Abstract Background. Representative data on the current management of patients with acute coronary syndromes (ACS) are of high interest. The EPICOR registry aimed to prospectively collect such real-life data with particular focus on antithrombotic drug utilization and outcomes. Methods. As part of the international prospective EPICOR registry, 29 hospitals in Germany documented 296 patients with ST-elevation myocardial infarction (STEMI)-ACS and 333 with unstable angina or non-STEMI (NSTEMI)-ACS surviving the hospital phase. The statistical analysis was performed in a descriptive manner. The ClinicalTrials.gov identifier is NCT01171404. Results. The mean age of patients was 62±13 years, and 77.4% were men. Treat-
ment with antithrombotic agents was initiated in the prehospital phase in 50.7% of STEMI and 33.3% of NSTEMI patients. During the hospital stay (median 7.0 days), cardiac catheterization was performed in 97.6%, percutaneous coronary intervention in 85.6%, thrombolysis in 4.6%, and coronary bypass surgery in 2.7% patients. The use of acetylic salicylic acid (ASA) was reported in 95.6% vs. 96.1%, clopidogrel in 60.8% vs. 73.0%, prasugrel in 45.6% vs. 22.5%, any GP IIb/IIIa inhibitor in 52.4% vs. 18.9% [any dual combination of ASA+(clopidogrel/prasugrel)in 94.0 vs. 91.0%], statins in 94.6% vs. 92.2%, beta blockers in 96.3% vs. 94.6%, and ACE-I/ARB in 91.6% vs. 87.7% of STEMI vs. NSTEMI patients, respectively. Combined use of the five drug classes recommended in the guidelines—
ASA, P2Y12 antagonists, statin, beta blocker, and ACE-I/ARB—was reported in 81.1% vs. 69.4% of STEMI vs. NSTEMI patients, respectively. Conclusion. In Germany a high proportion of patients with ACS are treated according to current guidelines, receiving primary revascularization as well as antithrombotic drugs and other agents for prevention of secondary events; associated bleeding complications were less frequent as compared with published registries. Keywords Acute coronary syndrome · Observation · Outcomes · Antithrombotic · Bleeding
Leitliniengerechte Therapie von Patienten mit akutem Koronarsyndrom. Das EPICOR-Register in Deutschland Zusammenfassung Hintergrund. Repräsentative Daten bezüglich der aktuellen Behandlung von Patienten mit akutem Koronarsyndrom („acute coronary syndrom“, ACS) sind von größtem Interesse. Das EPICOR-Register hat das Ziel, prospektive Real-life-Daten zu sammeln, mit besonderem Fokus auf die Verwendung antithrombotischer Medikamente und Outcomes. Methoden. Als Teil des internationalen prospektiven EPICOR-Registers haben 29 Kliniken in Deutschland 296 Patienten mit STEMI-ACS und 333 Patienten mit instabiler Angina pectoris oder NSTEMI-ACS dokumentiert, die die Krankenhausphase überlebten. Die statistische Analyse erfolgte deskriptiv. Die ClinicalTrials.gov Registriernummer ist NCT01171404. Ergebnisse. Das Durchschnittsalter der Patienten betrug 62±13 Jahre, 77,4% war-
Study variables and outcomes The main outcome variable is antithrombotic utilization patterns in STEMI and NSTEMI/UA patients during hospitalization and after discharge. Secondary prespecified outcomes include the associations of the most frequent antithrombotic drugs (alone or in combination) with the rates of clinical outcomes, levels of quali-
en Männer. Die Behandlung mit antithrombotischen Medikamenten wurde bei 50,7% der STEMI- und bei 33,3% der NSTEMI-Patienten in der prähospitalen Phase begonnen. Während des Krankenhausaufenthalts (Median: 7,0 Tage) wurde in 97,6% der Fälle eine kardiale Katheterisierung, in 85,6% eine perkutane koronare Intervention, in 4,6% eine Thrombolyse und in 2,7% eine Bypassoperation durchgeführt. Bei STEMI vs. NSTEMI wurde über die Anwendung von Acetylsalicylsäure (ASS) in 95,6% vs. 96,1% der Fälle berichtet, von Clopidogrel in 60,8% vs. 73,0%, von Prasugrel in 45,6% vs. 22,5%, von einem GP-IIb/IIIa-Inhibitor in 52,4% vs. 18,9% [eine beliebige Kombination von ASS + (Clopidogrel/Prasugrel) in 94,0% vs. 91,0%], von Statinen in 94,6 vs. 92,2%, von β-Blockern in 96,3% vs. 94,6% und von ACE-I/ARB in 91,6% vs. 87,7% der Fälle. Über eine kombinierte
ty of life and health resources consumption, the rates of antithrombotic treatment interruptions after discharge, their main causes and their clinical consequences. Clinical outcomes included ischemic events [myocardial infarction, UA, ischemic stroke, and transient ischemic attack (TIA)] and bleeding events during hospitalization. In-hospital events were adjudicated by the local investigators, but details
Anwendung der 5 in den Leitlinien empfohlenen Medikamentenklassen ASS, P2Y12-Antagonisten, Statine, β-Blocker und ACE-I/ ARB wurde bei 81,1% vs. 69,4% der Patienten berichtet. Schlussfolgerung. In Deutschland wird ein großer Teil der Patienten mit ACS gemäß den aktuellen Leitlinien behandelt, indem sie eine primäre Revaskularisation sowie antithrombotische Medikamente und andere Arzneimittel zur Prävention sekundärer Ereignisse erhalten. Blutungskomplikationen traten im Vergleich zu veröffentlichten Registern weniger häufig auf. Schlüsselwörter Akutes Koronarsyndrom · Beobachtung · Outcomes · Antithrombotisch · Blutung
for each bleeding event were adjudicated centrally (i.e., location, hemodynamic compromise, hemoglobin level, treatment required, etc.). Due to the noninterventional character of the study, there was no proactive collection of safety data, with the exception of treatment-associated bleeding events.
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Original article
Patient characteristics at baseline
Tab. 2 Prehospital medical management Prehospital care, reported in Time from symptom onset to first medical attention (h), median Time from symptom onset to first medical attention or prehospital ECG (h), median Killip class –I – II – III – IV – Unknown Any prehospital medication – Fibrinolysis – Acetylsalicylic acid – Clopidogrel – Prasugrel – GP IIb/IIIa inhibitor – Unfractionated heparin – Low-molecular-weight heparin – Fondaparinux
STEMI (N=296) n (%) 200 (67.6) 0.88
UA/NSTEMI (N=333) n (%) 170 (51.1) 1.60
Total (N=629) n (%) 370 (58.8) 1.15
1.06
1.62
1.25
189 (63.9) 20 (6.8) 1 (0.3) 3 (1.0) 83 (28.0) 150 (50.7) 2 (0.7) 147 (49.7) 39 (13.2) 4 (1.4) 2 (0.7) 142 (48.0) 2 (0.7) 0 (0.0)
230 (69.1) 20 (6.0) 3 (0.9) 2 (0.6) 78 (23.4) 111 (33.3) 0 (0.0) 106 (31.8) 23 (6.9) 3 (0.9) 0 (0.0) 98 (29.4) 4 (1.2) 1 (0.3)
419 (66.6) 40 (6.4) 4 (0.6) 5 (0.8) 161 (25.6) 261 (41.5) 2 (0.3) 253 (40.2) 62 (9.9) 7 (1.1) 2 (0.3) 240 (38.2) 6 (1.0) 1 (0.2)
NSTEMI non-ST-segment elevation myocardial infarction, STEMI ST-segment elevation myocardial infarction, UA unstable angina
Statistical considerations In the present analysis of data generated in Germany, the national subset of 29 centers and 629 patients was used. Continuous variables were summarized with descriptive statistics [absolute numbers (n), means, standard deviation (SD), or medians, with 25th and 75th percentile as appropriate]. Categorical data were described by the number (n) and percentage (%) of subjects in each category. Subgroups were formed according to STEMI and NSTEMI/UA criteria. No inferential statistical analyses were performed. The Statistical Analysis System (SAS Institute, Cary, N.C.), release 9.2 was used for analysis.
Results Site characteristics Of the 29 centers in Germany, 12 were university hospitals (41.4%), nine major community/regional hospitals (31.0%), seven nonuniversity general hospitals (24.1%), and one other type of hospital/clinic
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(3.4%). The size of the institutions varied considerably, as evidenced by the number of beds ranging from 77 to 1,500 (mean 457±351). All hospitals had a coronary/intensive care unit (100%), and 26 a coronary angiography catheterization laboratory (89.7%). Cardiac surgery was available in 15 sites (51.7%).
Inclusion process and patient flow A total of 629 ACS patients provided informed consent. The majority were treated at the primary hospital (534, 84.9%), while 72 patients (11.4%) were transferred to another hospital, and 23 patients (3.7%) transferred to another hospital and then back to the original institution. Reasons for transfer were primary PCI, rescue, or elective PCI in 82 patients. The median total length of hospital stay was 7.0 days (range, 2.0–39.0 days); in the STEMI group it was 8.0 days compared with 7.0 days in the NSTEMI group.
Almost all patients were Caucasian (99.4%). Men were more frequently seen with ACS than women were (77.4%/22.6%, . Tab. 1). The mean age of patients was 61.7±12.5 years (range, 33–89), and patients with STEMI were younger than those with NSTEMI (58.7 vs. 64.3 years). Hypertension, hypercholesterolemia, current smoking, and family history of CAD were the most frequent cardiovascular risk factors. In 35.0% of cases, cardiovascular disease was already known (in STEMI 19.3%, NSTEMI 48.9%); 5.1% had stroke/TIA and 7.2% peripheral arterial disease as other manifestations of atherothrombotic disease. Bleeding events and comorbidities possibly related to such events were rare within 6 months prior to the ACS index event; major bleeding was reported in two cases in the STEMI and three cases in the NSTEMI group (0.6% overall); however, none led to transfusion or surgical intervention.
Initial ACS presentation and prehospital management Median time from symptom onset to first medical attention was 69 min, and was shorter in the STEMI than in the NSTEMI group (53 min vs. 96 min, respectively, . Tab. 2). Most patients were classified as Killip class I (66.9%); however, in 25.6% the class was not identified. Prehospital medication for ACS was given to 41.5% of patients (STEMI 50.7% vs. NSTEMI 33.3%), most frequently acetylic salicylic acid (ASA) and/or unfractionated heparin.
In-hospital management . Tab. 3 displays interventions for ACS
during the hospital stay. Almost all patients received cardiac catheterization (97.6%); PCI was performed in 85.6% of patients (repeat procedures only in 8.0%), usually with reperfusion (PCI 85.4%, thrombolysis 4.6%), while acute CABG was the exception (2.7%). All procedures with the exception of CABG were reported more frequently in STEMI compared with NSTEMI patients. The median time
Tab. 3 In-hospital medical procedures and management Coronary angiography Number of procedures –1 –2 –3 Type of first procedure – Primary/direct – Routine early invasive strategy – Other Percutaneous coronary intervention (PCI) Coronary artery bypass graft Reperfusion (PCI and/or thrombolysis) Procedural results and features Vascular access, femoral Coronary stenosis >50% Number of vessels with disease –1 –2 –3 Left main disease Culprit lesion territory – Left main (LM) – Left anterior descending (LAD) – Left circumflex (LCX) – Right coronary arteries (RCA) Culprit artery TIMI flow occluded – TIMI 0/1 – TIMI 2 – Normal (TIMI 3) – Unknown Number of dilated vessels –0 –1 –2 – 3+ – Unknown Number of vessels successfully revascularized –0 –1 –2 – 3+ Number of stents –0 –1 –2 – 3+ Drug-eluting stent – Any –0 –1 –2 – 3+
STEMI (N=296) n (%) 295 (99.7)
UA/NSTEMI (N=333) n (%) 319 (95.8)
Total (N=629) n (%) 614 (97.6)
274 (92.9) 20 (6.8) 1 (0.3)
290 (90.9) 27 (8.5) 2 (0.6)
564 (91.9) 47 (7.7) 3 (0.5)
244 (82.7) 7 (2.4) 0 (0.0) 281 (94.9) 3 (1.0) 282 (95.3) 295 (99.7) 263 (89.2) 288 (97.6)
240 (75.2) 22 (6.9) 17 (5.3) 255 (76.6) 14 (4.2) 255 (76.6) 319 (95.8) 269 (84.3) 297 (93.1)
484 (78.8) 29 (4.7) 17 (2.8) 536 (85.2) 17 (2.7) 537 (85.4) 614 (97.6) 532 (86.6) 585 (95.3)
152 (51.5) 83 (28.1) 51 (17.3) 35 (11.9)
113 (35.4) 93 (29.2) 88 (27.6) 42 (13.2)
265 (43.2) 176 (28.7) 139 (22.6) 77 (12.5)
8 (2.7) 112 (38.0) 48 (16.3) 119 (40.3)
11 (3.4) 120 (37.6) 63 (19.7) 93 (29.2)
19 (3.1) 232 (37.8) 111 (18.1) 212 (34.5)
154 (52.2) 37 (12.5) 47 (15.9) 57 (19.3)
87 (27.3) 56 (17.6) 85 (26.6) 91 (28.5)
241 (39.3) 93 (15.1) 132 (21.5) 148 (24.1)
6 (2.0) 244 (82.7) 19 (6.4) 5 (1.7) 6 (2.0)
5 (1.6) 210 (65.8) 24 (7.5) 3 (0.9) 4 (1.3)
11 (1.8) 454 (73.9) 43 (7.0) 8 (1.3) 10 (1.6)
4 (1.4) 254 (86.1) 17 (5.8) 5 (1.7)
7 (2.2) 211 (66.1) 23 (7.2) 5 (1.6)
11 (1.8) 465 (75.7) 40 (6.5) 10 (1.6)
6 (2.0) 196 (66.4) 49 (16.6) 29 (9.8)
18 (5.6) 155 (48.6) 49 (15.4) 24 (7.5)
24 (3.9) 351 (57.2) 98 (16.0) 53 (8.6)
166 (56.3) 0 (0.0) 115 (39.0) 35 (11.9) 16 (5.4)
149 (46.7) 1 (0.3) 96 (30.1) 35 (11.0) 17 (5.3)
315 (51.3) 1 (0.2) 211 (34.4) 70 (11.4) 33 (5.4)
NSTEMI non-ST-segment elevation myocardial infarction, STEMI ST-segment elevation myocardial infarction, TIMI thrombolysis in myocardial infarction, UA unstable angina
Original article Tab. 4 Medication during hospitalization and at discharge
Antiplatelets Any ASA Clopidogrel Prasugrel GP IIb/IIIa Any Abciximab Eptifibatide Tirofiban Anticoagulant Any drug Total number, 1 Total number, 2 Total number, 3 Unfractionated heparin Low-molecular-weight heparin Bivalirudin Fondaparinux Warfarin/acenocoumarol Dabigatran Other CV therapy Any Beta blockers ACE inhibitor/ARB Statins Other lipid-lowering drugs Aldosterone inhibitors Diuretics – Loop diuretics – Non-loop diuretics Calcium channel blocker Other agent At least one non-CV therapy
STEMI (N=296) n (%) Hospital
Discharge
UA/NSTEMI (N=333) n (%) Hospital Discharge
Total (N=629) n (%) Hospital
Discharge
296 (100) 283 (95.6) 180 (60.8) 135 (45.6)
294 (99.3) 143 (48.3) 137 (46.3)
332 (99.7) 320 (96.1) 243 (73.0) 75 (22.5)
317 (95.2) 209 (62.8) 68 (20.4)
628 (99.8) 603 (95.9) 423 (67.2) 210 (33.4)
611 (97.1) 352 (56.0) 205 (32.6)
155 (52.4) 66 (22.3) 43 (14.5) 45 (15.2)
63 (18.9) 15 (4.5) 23 (6.9) 24 (7.2)
218 (34.7) 81 (12.9) 66 (10.5) 69 (11.0)
283 (95.6) 69 (23.3) 90 (30.4) 68 (23.0) 230 (77.7) 174 (58.8) 14 (4.7) 36 (12.2) 8 (2.7) 0 (0.0)
9 (3.0) 0 (0.0)
322 (96.7) 88 (26.4) 120 (36.0) 68 (20.4) 261 (78.4) 167 (50.2) 6 (1.8) 70 (21.0) 18 (5.4) 0 (0.0)
19 (5.7) 0 (0.0)
605 (96.2) 157 (25.0) 210 (33.4) 136 (21.6) 491 (78.1) 341 (54.2) 20 (3.2) 106 (16.9) 26 (4.1) 0 (0.0)
28 (4.5) 0 (0.0)
294 (99.3) 285 (96.3) 271 (91.6) 280 (94.6) 21 (7.1) 46 (15.5) 58 (19.6) 33 (11.1) 23 (7.8) 52 (17.6) 141 (47.6)
287 (97.0) 274 (92.6) 278 (93.9) 14 (4.7) 43 (14.5) 60 (20.3) 21 (7.1)
333 (100) 315 (94.6) 292 (87.7) 307 (92.2) 26 (7.8) 32 (9.6) 102 (30.6) 48 (14.4) 84 (25.2) 82 (24.6) 163 (48.9)
304 (91.3) 298 (89.5) 307 (92.2) 13 (3.9) 33 (9.9) 136 (40.8) 77 (23.1)
627 (99.7) 600 (95.4) 563 (89.5) 587 (93.3) 47 (7.5) 78 (12.4) 160 (25.4) 81 (12.9) 107 (17.0) 134 (21.3) 304 (48.3)
591 (94.0) 572 (90.9) 585 (93.0) 27 (4.3) 76 (12.1) 196 (31.2) 98 (15.6)
ASA acetylic salicylic acid ACE angiotensin-converting enzyme, ARB angiotensin receptor blocker, CV cardiovascular, NSTEMI non-ST-segment elevation myocardial infarction, STEMI ST-segment elevation myocardial infarction, UA unstable angina
from onset to first PCI was 7.4 h overall, but was much shorter in the STEMI than in the NSTEMI group (2.8 vs. 21.8 h). Femoral access was more frequently chosen than radial access (86.6% vs. 8.6%, in 4.7% not reported). Stents were reported in 79.8% of patients overall.
(9.2%), treadmill exercise in 48 patients (7.6%), angio-computed tomography in eight patients (1.3%), stress echocardiography in ten patients (1.6%), nuclear imaging in four patients (0.6%), and other examinations in 141 patients (22.4%).
Diagnostic procedures
Cardiovascular medication including antiplatelets
Diagnostic procedures were done before revascularization. They involved echocardiography in 541 patients (86.0%), magnetic resonance imaging in 58 patients
Statins, beta-blockers, and ACE inhibitors/ARBs, all of which are recommended for secondary prevention in ACS patients, were administered in over 90% of
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patients during hospitalization and at discharge (. Tab. 4). Use of acetylic salicylic acid (ASA) was reported in 95.6% vs. 96.1%, clopidogrel in 60.8% vs. 73.0%, prasugrel in 45.6% vs. 22.5%, and any GP IIb/IIIa inhibitor in 52.4% vs. 18.9% of STEMI vs. NSTEMI patients, respectively. A summary of the use of antiplatelet combinations during hospital stay is provided in . Fig. 1 and in . Tab. 4 and . Tab. 5. Any dual combination of ASA+ (clopidogrel/prasugrel) was used in 94.0% vs. 91.0% of STEMI vs. NSTEMI patients, respectively.
20
0
40
60
80
Total NSTEMI STEMI
64.7
ASA + Clopidogrel
100 %
70.6 58.1
32.1
ASA + Prasugrel
21.9 43.6
Discussion
92.0 91.0
Dual antiplatelet
94.0
32.1 16.8
Dual antiplatelet + GPIIb/IIIa
49.3
Fig. 1 8 Combinations of antiplatelet drugs during hospital stay. Antiplatelets: acetylic salicylic acid (ASA), clopidogrel, prasugrel, ticlopidine, or GP IIb/IIIa inhibitors. ACS acute coronary syndrome, NSTEMI non-ST-segment elevation myocardial infarction, STEMI ST-segment elevation myocardial infarction 0 Myocardial Infarction
1 0.3
Cardiogenic Shock
2
4
6
7
8 %
Total NSTEMI-ACS STEMI-ACS
1.4
0.6
1.3 2.0 1.9 2.1
1.7 1.3
Recurrent Ischemia
1.8
0.7 0.5 0.0
0.9 5.1
Bleeding Heart Failure
1.5
1.4
2.7
2.7
Sustained Ventricular Tachycardia
2.4 0.6
6.1
3.4
4.9
Atrial Fibrillation/Flutter
5.6
2.4 2.1
Dyspnea Other Causes*
High-Degree AV Block
5
0.8
Cardiac Arrest/VF
Stroke
3
6.9
3.0 3.7
1.6 2.7
Fig. 2 8 In-hospital outcomes of acute coronary syndrome (ACS) survivors. *Dyspnea not due to heart failure or cardiogenic shock. ACS acute coronary syndrome, NSTEMI non-ST-segment elevation myocardial infarction, STEMI ST-segment elevation myocardial infarction, VF ventricular fibrillation
Complications During hospitalization, recurrent ischemia was reported in 1.3%, recurrent myocardial infarction in 0.8%, cardiogen-
on 19 patients (3.0%; STEMI 2.7% vs. NSTEMI 3.3%), and cardiac surgery on 18 patients (2.9%; STEMI 1.4% vs. NSTEMI 1.8%). Hemorrhagic complications during hospitalization occurred in 35 cases (5.6%), and eight of these cases were nonminimal (. Tab. 6). Blood transfusions were required in 14 patients, and surgical vessel repair in three cases.
ic shock in 1.3%, and cardiac arrest in 1.9% of patients (. Fig. 2). Resuscitation was performed on 24 patients (overall 3.8%; STEMI 4.7% vs. NSTEMI 3.0%), mechanical ventilation
This contemporary registry is a representative sample of patients with ACS surviving the hospital stay and indicates a high therapeutic standard considering guideline-adherent management prior to and during hospitalization for ACS. The time to first medical attention was short in STEMI and NSTEMI (53 vs. 96 min, respectively) patients, and is shorter than, for example, in the French FAST-MI 2010 survey (time to first call or contact STEMI 74 vs. NSTEMI 105 min). In line with the high prevalence of PCI centers in Germany, the great majority of hospitals initiated in-house specific therapy, and only 15.1% of patients needed transfer to other hospitals potentially resulting in delayed intervention. Antithrombotic and antiplatelet drugs have increasingly become the mainstay of ACS management in line with current guidelines, leading to substantially improved outcomes. Antithrombotic agents were initiated in the prehospital phase in 50.7% of STEMI and 33.3% of NSTEMI patients. During hospital stay, almost all patients received such drugs, with a high proportion of dual antiplatelet combination therapy, and with no major differences between STEMI and NSTEMI patients. One third (34.5%) of the STEMI patients received two to four antiplatelet agents and three to four anticoagulants, indicating a lot of switching during the hospital stay. Of note, in the latest guidelines, the highest level of evidence in the group of antithrombotic agents in NSTEMI-ACS patients was assigned to fondaparinux (IA), and in STEMI-ACS patients to bivalirudin (IB), while the uptake of the data in EPICOR (and other sources) was very low. Further, the rates of other cardiovascular drugs as recommended in the Herz 2014
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Original article Tab. 5 Anticoagulant and antiplatelet use Group
Number of antiplateletsa
Total (N=629) STEMI (N=296) NSTEMI (N=333)
0 1 2–4 0 1 2–4 0 1 2–4
Number of anticoagulantsb 0–1 2 (0.3%) 21 (3.3%) 13 (2.1%) 0 (0%) 4 (1.35%) 4 (1.35%) 2 (0.6%) 17 (5.11%) 9 (2.7%)
2 9 (1.4%) 125 (19.9%) 229 (36.4%) 2 (0.7%) 34 (11.5%) 88 (29.7%) 7 (2.1%) 91 (27.3%) 141 (42.3%)
3–4 4 (0.6%) 83 (13.2%) 143 (22.7%) 2 (0.7%) 60 (20.3%) 102 (34.5%) 2 (0.6%) 23 (6.9%) 41 (12.3%)
aASA, clopidogrel, prasugrel, ticlopidine, or GP IIb/IIIa inhibitorsbUnfractionated heparin, low-molecular-weight
heparin, fondaparinux, or bivalirudin
Tab. 6 In-hospital bleedingsa Hemorrhagic complications Related to a medical procedure Clinical significance – Minimal – Nonminimal Hemodynamic compromise – Minimal – Nonminimal Bleeding management – Blood transfusion – Red blood Urgent surgery Interruption of antithrombotic therapy
STEMI (N=296) n (%) 18 (6.1) 10 (55.6)
UA/NSTEMI (N=333) n (%) 17 (5.1) 10 (58.8)
Total (N=629) n (%) 35 (5.6) 20 (57.1)
13 (72.2) 5 (27.8)
14 (82.4) 3 (17.6)
27 (77.1) 8 (22.9)
15 (83.3) 3 (16.7)
16 (94.1) 1 (5.9)
31 (88.6) 4 (11.4)
9 (50.0) 9 (50.0) 0 (0.0) 2 (11.1)
5 (29.4) 5 (29.4) 3 (17.6) 2 (11.8)
14 (40.0) 14 (40.0) 3 (8.6) 4 (11.4)
NSTEMI non-ST-segment elevation myocardial infarction, STEMI ST-segment elevation myocardial infarction, UA unstable anginaaA subject could be reported in multiple categories
ACS guidelines (beta blockers, ACE inhibitors or angiotensin receptor blockers, statins) surpassed 90% each and were (e.g., compared with the GRACE results [20]) among the highest reported to date during hospital stay and at discharge. The high prescription rates of beta blockers in patients with UA/NSTEMI might indicate overtreatment, as the ESC guidelines recommend these drugs in patients with left ventricular dysfunction. In view of possible contraindications (e.g., no beta blockers in patients in Killip class ≥ III [2]), it seems difficult to increase the respective treatment rates further. Overall the performance measures as explicitly stipulated in the NSTEMI guidelines were fulfilled to a high degree [2]. In this EPICOR cohort, the proportion of patients with bleeding complications was considerably lower (5.6% over-
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all, 2.2% of patients requiring transfusion), despite the fact that a high rate of dual antiplatelet therapy (± GP IIb/IIIa inhibitors) was reported. In other registries, major bleeding was a relatively frequent and severe event: for example, in the ACTION-GWTG in an analysis of 90,000 STEMI and NSTEMI patients, 10.7% had major bleeding during hospital stay [21]. The risk of major bleeding was increased by about 60% in patients with triple antiplatelet vs. dual therapy in an analysis of the GRACE registry [20]. Recent studies have identified major bleeding after PCI as an important predictor of increased mortality [22]. The great majority of patients received PCI (85.6%), while CABG (2.7%) and thrombolysis (4.6%) played only a minor role. This is in agreement with guideline recommendations for STEMI where prima-
ry angioplasty is superior to fibrinolysis if performed early [4], and for NSTEMI where invasive management is indicated in all patients except those at low risk [2]. Even in rural infarction networks, primary angioplasty has been reported to be feasible and efficient [23].
Conclusion Methodical considerations have to be taken into account when discussing the current data. The registry follows a naturalistic approach to avoid protocol-induced procedures or outcomes to achieve high external validity of the findings [19]. As participation in the study was on a voluntary basis, a “positive” selection of centers with interest in the topic and possibly over-average standards is likely [24], and centers with a low volume of ACS patients might be less inclined to participate [11]. As the inclusion period ended in March 2011, not all of the newer antithrombotic drugs mentioned in the ACS guidelines such as dabigatran were documented. Further, the registry did not capture data on ACS patients who died during their hospital stay (usually older and sicker patients), which impacts survival rates. Lastly, the present cohort was rather small and thus subject to various unaccounted confounders typical for such an analysis.
Corresponding address Prof. Dr. U. Zeymer Klinikum Ludwigshafen Bremser Str. 79, 67063 Ludwigshafen Germany [email protected]
Acknowledgments. The study was financially supported by Astra Zeneca.
Compliance with ethical guidelines Conflict of interest. U. Zeymer, H. Heuer, P. Schwimmbeck, S. Genth-Zotz, K. Wolff, and C.A. Nienaber state that there are no conflicts of interest. All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.
References 1. Statistisches Bundesamt Deutschland Ten leading causes of mortality 2012 in Germany (Todesursachen: Sterbefälle insgesamt 2012 nach den 10 häufigsten Todesursachen der International Statistical Classification of Diseases and Related Health Problems (ICD-10)). https://www.destatis.de/DE/ ZahlenFakten/GesellschaftStaat/Gesundheit/ Todesursachen/Tabellen/SterbefaelleInsgesamt. html. Accessed 25 Aug 2014 2. Hamm CW, Bassand JP, Agewall S et al (2011) ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 32(23):2999–3054 3. Thygesen K, Alpert JS, Jaffe AS et al (2012) Third universal definition of myocardial infarction. Eur Heart J 33(20):2551–2567 4. Steg PG, James SK, Atar D et al (2012) ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 33(20):2569–2619 5. Wijns W, Kolh P, Danchin N et al (2010) Guidelines on myocardial revascularization. Eur Heart J 31(20):2501–2555 6. Brieger D (2012) Antithrombotic strategies to reduce adverse clinical outcomes in patients with acute coronary syndrome. Am J Cardiol 110(8):1200–1206 7. Eggers KM, Kempf T, Venge P et al (2010) Improving long-term risk prediction in patients with acute chest pain: the Global Registry of Acute Coronary Events (GRACE) risk score is enhanced by selected nonnecrosis biomarkers. Am Heart J 160(1):88–94 8. Goodman SG, Huang W, Yan AT et al (2009) The expanded Global Registry of Acute Coronary Events: baseline characteristics, management practices, and hospital outcomes of patients with acute coronary syndromes. Am Heart J 158(2):193–201 e191–195 9. Lewis WR, Peterson ED, Cannon CP et al (2008) An organized approach to improvement in guideline adherence for acute myocardial infarction: results with the get with the guidelines quality improvement program. Arch Intern Med 168(16):1813– 1819 10. Yan AT, Yan RT, Huynh T et al (2009) Understanding physicians’ risk stratification of acute coronary syndromes: insights from the Canadian ACS 2 Registry. Arch Intern Med 169(4):372–378 11. Hanssen M, Cottin Y, Khalife K et al (2012) French registry on acute ST-elevation and non ST-elevation myocardial infarction 2010. FAST-MI 2010. Heart 98(9):699–705 12. Sciahbasi A, Rizzello V, Gonzini L et al (2014) Chronic aspirin and statin therapy in patients with impaired renal function and acute coronary syndromes: results from the IN-ACS outcome registry. Eur J Prev Cardiol 21(2):214–221 13. Stauffer JC, Goy JJ, Duvoisin N et al (2012) Dramatic effect of early clopidogrel administration in reducing mortality and MACE rates in ACS patients. Data from the Swiss registry AMIS-Plus. Swiss Med Wkly 142:w13573 14. Kirchberger I, Meisinger C, Heier M et al (2011) Patient-reported symptoms in acute myocardial infarction: differences related to ST-segment elevation: the MONICA/KORA myocardial infarction registry. J Intern Med 270(1):58–64
15. Hailer B, Naber C, Koslowski B et al (2011) Gender-related differences in patients with ST-elevation myocardial infarction: results from the registry study of the ST elevation myocardial infarction network Essen. Clin Cardiol 34(5):294–301 16. Ndrepepa G, Mehilli J, Schulz S et al (2009) Patterns of presentation and outcomes of patients with acute coronary syndromes. Cardiology 113(3):198–206 17. Bauer T, Hoffmann R, Junger C et al (2009) Efficacy of a 24-h primary percutaneous coronary intervention service on outcome in patients with ST elevation myocardial infarction in clinical practice. Clin Res Cardiol 98(3):171–178 18. Schwarz AK, Zahn R, Hochadel M et al (2011) Agerelated differences in antithrombotic therapy, success rate and in-hospital mortality in patients undergoing percutaneous coronary intervention: results of the quality control registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte (ALKK). Clin Res Cardiol 100(9):773–780 19. Bueno H, Danchin N, Tafalla M et al (2013) EPICOR (long-tErm follow-up of antithrombotic management Patterns In acute CORonary syndrome patients) study: rationale, design, and baseline characteristics. Am Heart J 165(1):8–14 20. Lim MJ, Eagle KA, Gore JM et al (2005) Treating patients with acute coronary syndromes with aggressive antiplatelet therapy (from the Global Registry of Acute Coronary Events). Am J Cardiol 96(7):917– 921 21. Mathews R, Peterson ED, Chen AY et al (2011) Inhospital major bleeding during ST-elevation and non-ST-elevation myocardial infarction care: derivation and validation of a model from the ACTION Registry(R)-GWTG. Am J Cardiol 107(8):1136–1143 22. Doyle BJ, Ting HH, Bell MR et al (2008) Major femoral bleeding complications after percutaneous coronary intervention: incidence, predictors, and impact on long-term survival among 17,901 patients treated at the Mayo Clinic from 1994 to 2005. JACC Cardiovasc Interv 1(2):202–209 23. Birkemeyer R, Rillig A, Koch A et al (2010) Primary angioplasty for any patient with ST-elevation myocardial infarction? Guideline-adherent feasibility and impact on mortality in a rural infarction network. Clin Res Cardiol 99(12):833–840 24. Delgado-Rodriguez M, Llorca J (2004) Bias. J Epidemiol Community Health 58(8):635–641
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U. Zeymer1, 2 · H. Heuer3 · P. Schwimmbeck4 · S. Genth-Zotz5 · K. Wolff6 · C.A. Nienaber7 · The EPICOR Investigators 1 Klinikum Ludwigshafen, Ludwigshafen 2 Institut für Herzinfarktforschung, Ludwigshafen 3 Klinik für Innere Medizin I, St. Johannes-Hospital gGmbH, Dortmund 4 Klinik für Kardiologie, Klinikum Leverkusen, Leverkusen 5 Klinik für Innere Medizin I, Katholisches Klinikum Mainz, Mainz 6 Medizinische Abteilung, AstraZeneca GmbH, Wedel 7 Universitäres Herzzentrum Rostock, Universitätsmedizin Rostock, Rostock
Guideline-adherent therapy in patients with acute coronary syndromes The EPICOR registry in Germany
Despite sustained research efforts and clinical progress, cardiovascular diseases are still among the leading causes for death and morbidity in industrialized countries including Germany [1]. Among these, acute coronary syndrome (ACS) is a highly prevalent manifestation. The spectrum of ACS comprises, based on ECG criteria and troponin measurements, STsegment elevation (STEMI) and nonST-segment elevation myocardial infarction (NSTEMI) as well as unstable angina (UA) [2]. While the spectrum of conditions shares many pathophysiological similarities [3], management differs to a certain extent, reflected in the development of heterogeneous guidelines by the European Society for Cardiology and associated societies [2, 4, 5]. Nonetheless, antithrombotic agents are the mainstay therapy for all manifestations of ACS [6]. In agreement with the importance of ACS, a substantial body of data from observational studies and registries has been collected in projects such as the Global Registry of Acute Coronary Events (GRACE [7, 8]), and various national projects such as the US American Get with the Guidelines registry (GWTG [9]), the Canadian ACS-2 registry [10], the French FAST-MI
2010 registry [11], the Italian IN-ACS Outcome registry [12] or the Swiss AMIS-plus registry [13]. In Germany, ACS registries are partially limited to certain geographic areas such as the MONICA/CORA Myocardial Infarction registry in the Augsburg area [14], the Myocardial Infarction Network Essen [15], the German Heart Centre ACS registry [16], and national efforts such as the German Acute Coronary Syndromes registry (ACOS) [17] or, more recently, the quality control registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte (ALKK) [18]. In recent years, substantial progress has been made in the management of ACS, due to structural improvements (leading to reduced admission times), optimized interventional procedures, and also availability of new antithrombotic agents that are used alone or in combinations [6]. Thus, there is a need for current and representative observational data on utilization and patient outcomes. The EPICOR (Long-Term Follow-Up of Antithrombotic Management Patterns in Acute Coronary Syndrome Patients) was set up to generate a snapshot of such real-life data. In this article, we present the baseline data of the German cohort, with a descriptive
comparison between STEMI and NSTEMI/UA patients with regard to management and in-hospital outcomes. During the course of the study, the NSTEMI-ACS guidelines [2] were updated mid-2011 and the STEMI-ACS ESC guidelines in 2012 [4].
Methods Design EPICOR is a prospective, open, observational, nonrandomized cohort study conducted in 555 centers in 20 countries of four geographic regions (Northern Europe, Southern Europe, Eastern Europe, and Latin America). The recruitment phase was from September 2010 to March 2011, while the follow-up phase of study is on-going; 629 patients were included in Germany. The rationale, design, and aims of the study were described in greater detail recently [19]. In brief, participating centers were selected to achieve a sample of representative patients with ACS receiving antithrombotic management in their respective country. This study was conducted in accordance with the EU Note Herz 2014
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Original article Tab. 1 Demographics, medical history, and comorbidities
STEMI (N=296) n (%)
UA/NSTEMI (N=333) n (%)
Age, years ± SD Gender – Male – Female CV risk factors, any – Hypertension – Hypercholesterolemia – Diabetes mellitus – Family history of CVD – Smoking, current – Smoking, former – Obesity: BMI >30 kg/m2 Previous CVD – Myocardial infarction – Prior PCI – Prior CABG – Chronic angina – Heart failure – Atrial fibrillation – TIA/Stroke – Peripheral vascular disease Previous non-CVD disease, any – Chronic renal failure – COPD or other chronic lung disease – Severe liver disease – Esophageal varices – Major surgerya
58.7±12.0 229 (77.4) 67 (22.6) 248 (83.8) 177 (59.8) 159 (53.7) 48 (16.2) 118 (39.9) 137 (46.3) 62 (20.9) 76 (25.7) 57 (19.3) 20 (6.8) 27 (9.1) 7 (2.4) 9 (3.0) 8 (2.7) 7 (2.4) 10 (3.4) 12 (4.1) 79 (26.7) 9 (3.0) 23 (7.8) 1 (0.3%) 2 (0.7%) 3 (1.0%)
64.3±12.4 258 (77.5) 75 (22.5) 314 (94.3) 265 (79.6) 200 (60.1) 84 (25.2) 117 (35.1) 104 (31.2) 102 (30.6) 108 (32.4) 163 (48.9) 89 (26.7) 105 (31.5) 40 (12.0) 30 (9.0) 26 (7.8) 29 (8.7) 22 (6.6) 33 (9.9) 132 (39.6) 37 (11.1) 30 (9.0) 2 (0.6%) 0 (0.0%) 7 (2.1%)
Total (N=629) n (%) 61.7±12.5 487 (77.4) 142 (22.6) 562 (89.3) 442 (70.3) 359 (57.1) 132 (21.0) 235 (37.4) 241 (38.3) 164 (26.1) 184 (29.3) 220 (35.0) 109 (17.3) 132 (21.0) 47 (7.5) 39 (6.2) 34 (5.4) 36 (5.7) 32 (5.1) 45 (7.2) 211 (33.5) 46 (7.3) 53 (8.4) 3 (0.5%) 2 (0.3%) 10 (1.6%)
BMI body mass index, CABG coronary artery bypass graft, COPD chronic obstructive pulmonary disease, CV cardiovascular, CVD cardiovascular disease, NSTEMI non-ST-segment elevation myocardial infarction, SD standard deviation, STEMI ST-segment elevation myocardial infarction, TIA transient ischemic attack, UA unstable anginaaIn the 6 months prior to the index ACS event. None of the bleeding events was related to a medical/ surgical procedure
for Guidance on Good Clinical Practice CPMP/ECH/135/95, the Declaration of Helsinki revision, and applicable legislation for noninterventional studies. Since only hospital survivors were included, patients gave written informed consent prior to discharge. EPICOR was initiated at the site level only after local and ethics approval requirements had been obtained. Emphasis was placed on consecutive enrolment of patients at each site. The study was planned, steered, and its data interpreted and disseminated by a scientific committee [19] consisting of representatives from each country. The study is registered in ClinicalTrials.gov under the identifier NCT01171404.
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Patients Men and women of 18 years or older were eligible if they met the following criteria: (1) hospitalization within 24 h of onset of symptoms of the index event for the first time, with a final (discharge) diagnosis of STEMI or NSTEMI/UA, (2) written informed consent at the time of hospital discharge, (3) completion of a Contact Order Form, on which they agreed to be contacted by telephone for regular follow-up interviews during the postdischarge phase. Patients were excluded if (1) ACS was precipitated by or was a complication of surgery, trauma, gastrointestinal bleeding, or postpercutaneous coronary intervention (PCI); (2) ACS occurred during hospitalization for other reasons; (3)
any condition/circumstance which, in the opinion of the investigator, could significantly limit the complete follow-up of the patient was present (e.g., tourist, nonnative speaker or other insufficient understanding of the local language; psychiatric disturbances); (4) previous enrolment in the EPICOR study; (5) currently participating in another clinical trial; or (6) presence of serious/severe comorbidities which, in the opinion of the investigator, would limit short-term (i.e., 6-month) life expectancy. ACS definitions were as follows: F STEMI—Chest pain/discomfort and persistent ST-segment elevation (>30 min) of ≥0.1 mV in two or more contiguous ECG leads or presumed new left bundle branch block (LBBB) on admission, and elevation of cardiac biomarkers (CK-MB, troponins) at least one value above the 99th percentile of the upper reference limit. F NSTEMI—Chest pain/discomfort, and lack of persistent ST-segment elevation, LBBB or intraventricular conduction disturbances, and elevation of cardiac biomarkers (CK-MB, troponins) at least one value above the 99th percentile of the upper reference limit. F UA—Symptoms of angina at rest or on minimal exercise, and transient ST-T changes, and no significant increase in biomarkers of necrosis but objective evidence of ischemia by noninvasive imaging or significant coronary stenosis at angiography. Major bleeding events in the 6 months preceding the index event were bleedings that required hospitalization or urgent medical care and/or blood transfusion and/or caused a significant hematocrit drop in the previous 6 months.
Data collection Data were collected in an electronic case report form (eCRF), at baseline (admission to hospital), at discharge from hospital, and at follow-up telephone contacts made by well-trained interviewers (follow-up data not reported here). No onsite monitoring with source data verification was performed.
Abstract · Zusammenfassung Herz 2014 · [jvn]:[afp]–[alp] DOI 10.1007/s00059-014-4161-7 © Urban & Vogel 2014 U. Zeymer · H. Heuer · P. Schwimmbeck · S. Genth-Zotz · K. Wolff · C.A. Nienaber · The EPICOR Investigators
Guideline-adherent therapy in patients with acute coronary syndromes. The EPICOR registry in Germany Abstract Background. Representative data on the current management of patients with acute coronary syndromes (ACS) are of high interest. The EPICOR registry aimed to prospectively collect such real-life data with particular focus on antithrombotic drug utilization and outcomes. Methods. As part of the international prospective EPICOR registry, 29 hospitals in Germany documented 296 patients with ST-elevation myocardial infarction (STEMI)-ACS and 333 with unstable angina or non-STEMI (NSTEMI)-ACS surviving the hospital phase. The statistical analysis was performed in a descriptive manner. The ClinicalTrials.gov identifier is NCT01171404. Results. The mean age of patients was 62±13 years, and 77.4% were men. Treat-
ment with antithrombotic agents was initiated in the prehospital phase in 50.7% of STEMI and 33.3% of NSTEMI patients. During the hospital stay (median 7.0 days), cardiac catheterization was performed in 97.6%, percutaneous coronary intervention in 85.6%, thrombolysis in 4.6%, and coronary bypass surgery in 2.7% patients. The use of acetylic salicylic acid (ASA) was reported in 95.6% vs. 96.1%, clopidogrel in 60.8% vs. 73.0%, prasugrel in 45.6% vs. 22.5%, any GP IIb/IIIa inhibitor in 52.4% vs. 18.9% [any dual combination of ASA+(clopidogrel/prasugrel)in 94.0 vs. 91.0%], statins in 94.6% vs. 92.2%, beta blockers in 96.3% vs. 94.6%, and ACE-I/ARB in 91.6% vs. 87.7% of STEMI vs. NSTEMI patients, respectively. Combined use of the five drug classes recommended in the guidelines—
ASA, P2Y12 antagonists, statin, beta blocker, and ACE-I/ARB—was reported in 81.1% vs. 69.4% of STEMI vs. NSTEMI patients, respectively. Conclusion. In Germany a high proportion of patients with ACS are treated according to current guidelines, receiving primary revascularization as well as antithrombotic drugs and other agents for prevention of secondary events; associated bleeding complications were less frequent as compared with published registries. Keywords Acute coronary syndrome · Observation · Outcomes · Antithrombotic · Bleeding
Leitliniengerechte Therapie von Patienten mit akutem Koronarsyndrom. Das EPICOR-Register in Deutschland Zusammenfassung Hintergrund. Repräsentative Daten bezüglich der aktuellen Behandlung von Patienten mit akutem Koronarsyndrom („acute coronary syndrom“, ACS) sind von größtem Interesse. Das EPICOR-Register hat das Ziel, prospektive Real-life-Daten zu sammeln, mit besonderem Fokus auf die Verwendung antithrombotischer Medikamente und Outcomes. Methoden. Als Teil des internationalen prospektiven EPICOR-Registers haben 29 Kliniken in Deutschland 296 Patienten mit STEMI-ACS und 333 Patienten mit instabiler Angina pectoris oder NSTEMI-ACS dokumentiert, die die Krankenhausphase überlebten. Die statistische Analyse erfolgte deskriptiv. Die ClinicalTrials.gov Registriernummer ist NCT01171404. Ergebnisse. Das Durchschnittsalter der Patienten betrug 62±13 Jahre, 77,4% war-
Study variables and outcomes The main outcome variable is antithrombotic utilization patterns in STEMI and NSTEMI/UA patients during hospitalization and after discharge. Secondary prespecified outcomes include the associations of the most frequent antithrombotic drugs (alone or in combination) with the rates of clinical outcomes, levels of quali-
en Männer. Die Behandlung mit antithrombotischen Medikamenten wurde bei 50,7% der STEMI- und bei 33,3% der NSTEMI-Patienten in der prähospitalen Phase begonnen. Während des Krankenhausaufenthalts (Median: 7,0 Tage) wurde in 97,6% der Fälle eine kardiale Katheterisierung, in 85,6% eine perkutane koronare Intervention, in 4,6% eine Thrombolyse und in 2,7% eine Bypassoperation durchgeführt. Bei STEMI vs. NSTEMI wurde über die Anwendung von Acetylsalicylsäure (ASS) in 95,6% vs. 96,1% der Fälle berichtet, von Clopidogrel in 60,8% vs. 73,0%, von Prasugrel in 45,6% vs. 22,5%, von einem GP-IIb/IIIa-Inhibitor in 52,4% vs. 18,9% [eine beliebige Kombination von ASS + (Clopidogrel/Prasugrel) in 94,0% vs. 91,0%], von Statinen in 94,6 vs. 92,2%, von β-Blockern in 96,3% vs. 94,6% und von ACE-I/ARB in 91,6% vs. 87,7% der Fälle. Über eine kombinierte
ty of life and health resources consumption, the rates of antithrombotic treatment interruptions after discharge, their main causes and their clinical consequences. Clinical outcomes included ischemic events [myocardial infarction, UA, ischemic stroke, and transient ischemic attack (TIA)] and bleeding events during hospitalization. In-hospital events were adjudicated by the local investigators, but details
Anwendung der 5 in den Leitlinien empfohlenen Medikamentenklassen ASS, P2Y12-Antagonisten, Statine, β-Blocker und ACE-I/ ARB wurde bei 81,1% vs. 69,4% der Patienten berichtet. Schlussfolgerung. In Deutschland wird ein großer Teil der Patienten mit ACS gemäß den aktuellen Leitlinien behandelt, indem sie eine primäre Revaskularisation sowie antithrombotische Medikamente und andere Arzneimittel zur Prävention sekundärer Ereignisse erhalten. Blutungskomplikationen traten im Vergleich zu veröffentlichten Registern weniger häufig auf. Schlüsselwörter Akutes Koronarsyndrom · Beobachtung · Outcomes · Antithrombotisch · Blutung
for each bleeding event were adjudicated centrally (i.e., location, hemodynamic compromise, hemoglobin level, treatment required, etc.). Due to the noninterventional character of the study, there was no proactive collection of safety data, with the exception of treatment-associated bleeding events.
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Original article
Patient characteristics at baseline
Tab. 2 Prehospital medical management Prehospital care, reported in Time from symptom onset to first medical attention (h), median Time from symptom onset to first medical attention or prehospital ECG (h), median Killip class –I – II – III – IV – Unknown Any prehospital medication – Fibrinolysis – Acetylsalicylic acid – Clopidogrel – Prasugrel – GP IIb/IIIa inhibitor – Unfractionated heparin – Low-molecular-weight heparin – Fondaparinux
STEMI (N=296) n (%) 200 (67.6) 0.88
UA/NSTEMI (N=333) n (%) 170 (51.1) 1.60
Total (N=629) n (%) 370 (58.8) 1.15
1.06
1.62
1.25
189 (63.9) 20 (6.8) 1 (0.3) 3 (1.0) 83 (28.0) 150 (50.7) 2 (0.7) 147 (49.7) 39 (13.2) 4 (1.4) 2 (0.7) 142 (48.0) 2 (0.7) 0 (0.0)
230 (69.1) 20 (6.0) 3 (0.9) 2 (0.6) 78 (23.4) 111 (33.3) 0 (0.0) 106 (31.8) 23 (6.9) 3 (0.9) 0 (0.0) 98 (29.4) 4 (1.2) 1 (0.3)
419 (66.6) 40 (6.4) 4 (0.6) 5 (0.8) 161 (25.6) 261 (41.5) 2 (0.3) 253 (40.2) 62 (9.9) 7 (1.1) 2 (0.3) 240 (38.2) 6 (1.0) 1 (0.2)
NSTEMI non-ST-segment elevation myocardial infarction, STEMI ST-segment elevation myocardial infarction, UA unstable angina
Statistical considerations In the present analysis of data generated in Germany, the national subset of 29 centers and 629 patients was used. Continuous variables were summarized with descriptive statistics [absolute numbers (n), means, standard deviation (SD), or medians, with 25th and 75th percentile as appropriate]. Categorical data were described by the number (n) and percentage (%) of subjects in each category. Subgroups were formed according to STEMI and NSTEMI/UA criteria. No inferential statistical analyses were performed. The Statistical Analysis System (SAS Institute, Cary, N.C.), release 9.2 was used for analysis.
Results Site characteristics Of the 29 centers in Germany, 12 were university hospitals (41.4%), nine major community/regional hospitals (31.0%), seven nonuniversity general hospitals (24.1%), and one other type of hospital/clinic
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(3.4%). The size of the institutions varied considerably, as evidenced by the number of beds ranging from 77 to 1,500 (mean 457±351). All hospitals had a coronary/intensive care unit (100%), and 26 a coronary angiography catheterization laboratory (89.7%). Cardiac surgery was available in 15 sites (51.7%).
Inclusion process and patient flow A total of 629 ACS patients provided informed consent. The majority were treated at the primary hospital (534, 84.9%), while 72 patients (11.4%) were transferred to another hospital, and 23 patients (3.7%) transferred to another hospital and then back to the original institution. Reasons for transfer were primary PCI, rescue, or elective PCI in 82 patients. The median total length of hospital stay was 7.0 days (range, 2.0–39.0 days); in the STEMI group it was 8.0 days compared with 7.0 days in the NSTEMI group.
Almost all patients were Caucasian (99.4%). Men were more frequently seen with ACS than women were (77.4%/22.6%, . Tab. 1). The mean age of patients was 61.7±12.5 years (range, 33–89), and patients with STEMI were younger than those with NSTEMI (58.7 vs. 64.3 years). Hypertension, hypercholesterolemia, current smoking, and family history of CAD were the most frequent cardiovascular risk factors. In 35.0% of cases, cardiovascular disease was already known (in STEMI 19.3%, NSTEMI 48.9%); 5.1% had stroke/TIA and 7.2% peripheral arterial disease as other manifestations of atherothrombotic disease. Bleeding events and comorbidities possibly related to such events were rare within 6 months prior to the ACS index event; major bleeding was reported in two cases in the STEMI and three cases in the NSTEMI group (0.6% overall); however, none led to transfusion or surgical intervention.
Initial ACS presentation and prehospital management Median time from symptom onset to first medical attention was 69 min, and was shorter in the STEMI than in the NSTEMI group (53 min vs. 96 min, respectively, . Tab. 2). Most patients were classified as Killip class I (66.9%); however, in 25.6% the class was not identified. Prehospital medication for ACS was given to 41.5% of patients (STEMI 50.7% vs. NSTEMI 33.3%), most frequently acetylic salicylic acid (ASA) and/or unfractionated heparin.
In-hospital management . Tab. 3 displays interventions for ACS
during the hospital stay. Almost all patients received cardiac catheterization (97.6%); PCI was performed in 85.6% of patients (repeat procedures only in 8.0%), usually with reperfusion (PCI 85.4%, thrombolysis 4.6%), while acute CABG was the exception (2.7%). All procedures with the exception of CABG were reported more frequently in STEMI compared with NSTEMI patients. The median time
Tab. 3 In-hospital medical procedures and management Coronary angiography Number of procedures –1 –2 –3 Type of first procedure – Primary/direct – Routine early invasive strategy – Other Percutaneous coronary intervention (PCI) Coronary artery bypass graft Reperfusion (PCI and/or thrombolysis) Procedural results and features Vascular access, femoral Coronary stenosis >50% Number of vessels with disease –1 –2 –3 Left main disease Culprit lesion territory – Left main (LM) – Left anterior descending (LAD) – Left circumflex (LCX) – Right coronary arteries (RCA) Culprit artery TIMI flow occluded – TIMI 0/1 – TIMI 2 – Normal (TIMI 3) – Unknown Number of dilated vessels –0 –1 –2 – 3+ – Unknown Number of vessels successfully revascularized –0 –1 –2 – 3+ Number of stents –0 –1 –2 – 3+ Drug-eluting stent – Any –0 –1 –2 – 3+
STEMI (N=296) n (%) 295 (99.7)
UA/NSTEMI (N=333) n (%) 319 (95.8)
Total (N=629) n (%) 614 (97.6)
274 (92.9) 20 (6.8) 1 (0.3)
290 (90.9) 27 (8.5) 2 (0.6)
564 (91.9) 47 (7.7) 3 (0.5)
244 (82.7) 7 (2.4) 0 (0.0) 281 (94.9) 3 (1.0) 282 (95.3) 295 (99.7) 263 (89.2) 288 (97.6)
240 (75.2) 22 (6.9) 17 (5.3) 255 (76.6) 14 (4.2) 255 (76.6) 319 (95.8) 269 (84.3) 297 (93.1)
484 (78.8) 29 (4.7) 17 (2.8) 536 (85.2) 17 (2.7) 537 (85.4) 614 (97.6) 532 (86.6) 585 (95.3)
152 (51.5) 83 (28.1) 51 (17.3) 35 (11.9)
113 (35.4) 93 (29.2) 88 (27.6) 42 (13.2)
265 (43.2) 176 (28.7) 139 (22.6) 77 (12.5)
8 (2.7) 112 (38.0) 48 (16.3) 119 (40.3)
11 (3.4) 120 (37.6) 63 (19.7) 93 (29.2)
19 (3.1) 232 (37.8) 111 (18.1) 212 (34.5)
154 (52.2) 37 (12.5) 47 (15.9) 57 (19.3)
87 (27.3) 56 (17.6) 85 (26.6) 91 (28.5)
241 (39.3) 93 (15.1) 132 (21.5) 148 (24.1)
6 (2.0) 244 (82.7) 19 (6.4) 5 (1.7) 6 (2.0)
5 (1.6) 210 (65.8) 24 (7.5) 3 (0.9) 4 (1.3)
11 (1.8) 454 (73.9) 43 (7.0) 8 (1.3) 10 (1.6)
4 (1.4) 254 (86.1) 17 (5.8) 5 (1.7)
7 (2.2) 211 (66.1) 23 (7.2) 5 (1.6)
11 (1.8) 465 (75.7) 40 (6.5) 10 (1.6)
6 (2.0) 196 (66.4) 49 (16.6) 29 (9.8)
18 (5.6) 155 (48.6) 49 (15.4) 24 (7.5)
24 (3.9) 351 (57.2) 98 (16.0) 53 (8.6)
166 (56.3) 0 (0.0) 115 (39.0) 35 (11.9) 16 (5.4)
149 (46.7) 1 (0.3) 96 (30.1) 35 (11.0) 17 (5.3)
315 (51.3) 1 (0.2) 211 (34.4) 70 (11.4) 33 (5.4)
NSTEMI non-ST-segment elevation myocardial infarction, STEMI ST-segment elevation myocardial infarction, TIMI thrombolysis in myocardial infarction, UA unstable angina
Original article Tab. 4 Medication during hospitalization and at discharge
Antiplatelets Any ASA Clopidogrel Prasugrel GP IIb/IIIa Any Abciximab Eptifibatide Tirofiban Anticoagulant Any drug Total number, 1 Total number, 2 Total number, 3 Unfractionated heparin Low-molecular-weight heparin Bivalirudin Fondaparinux Warfarin/acenocoumarol Dabigatran Other CV therapy Any Beta blockers ACE inhibitor/ARB Statins Other lipid-lowering drugs Aldosterone inhibitors Diuretics – Loop diuretics – Non-loop diuretics Calcium channel blocker Other agent At least one non-CV therapy
STEMI (N=296) n (%) Hospital
Discharge
UA/NSTEMI (N=333) n (%) Hospital Discharge
Total (N=629) n (%) Hospital
Discharge
296 (100) 283 (95.6) 180 (60.8) 135 (45.6)
294 (99.3) 143 (48.3) 137 (46.3)
332 (99.7) 320 (96.1) 243 (73.0) 75 (22.5)
317 (95.2) 209 (62.8) 68 (20.4)
628 (99.8) 603 (95.9) 423 (67.2) 210 (33.4)
611 (97.1) 352 (56.0) 205 (32.6)
155 (52.4) 66 (22.3) 43 (14.5) 45 (15.2)
63 (18.9) 15 (4.5) 23 (6.9) 24 (7.2)
218 (34.7) 81 (12.9) 66 (10.5) 69 (11.0)
283 (95.6) 69 (23.3) 90 (30.4) 68 (23.0) 230 (77.7) 174 (58.8) 14 (4.7) 36 (12.2) 8 (2.7) 0 (0.0)
9 (3.0) 0 (0.0)
322 (96.7) 88 (26.4) 120 (36.0) 68 (20.4) 261 (78.4) 167 (50.2) 6 (1.8) 70 (21.0) 18 (5.4) 0 (0.0)
19 (5.7) 0 (0.0)
605 (96.2) 157 (25.0) 210 (33.4) 136 (21.6) 491 (78.1) 341 (54.2) 20 (3.2) 106 (16.9) 26 (4.1) 0 (0.0)
28 (4.5) 0 (0.0)
294 (99.3) 285 (96.3) 271 (91.6) 280 (94.6) 21 (7.1) 46 (15.5) 58 (19.6) 33 (11.1) 23 (7.8) 52 (17.6) 141 (47.6)
287 (97.0) 274 (92.6) 278 (93.9) 14 (4.7) 43 (14.5) 60 (20.3) 21 (7.1)
333 (100) 315 (94.6) 292 (87.7) 307 (92.2) 26 (7.8) 32 (9.6) 102 (30.6) 48 (14.4) 84 (25.2) 82 (24.6) 163 (48.9)
304 (91.3) 298 (89.5) 307 (92.2) 13 (3.9) 33 (9.9) 136 (40.8) 77 (23.1)
627 (99.7) 600 (95.4) 563 (89.5) 587 (93.3) 47 (7.5) 78 (12.4) 160 (25.4) 81 (12.9) 107 (17.0) 134 (21.3) 304 (48.3)
591 (94.0) 572 (90.9) 585 (93.0) 27 (4.3) 76 (12.1) 196 (31.2) 98 (15.6)
ASA acetylic salicylic acid ACE angiotensin-converting enzyme, ARB angiotensin receptor blocker, CV cardiovascular, NSTEMI non-ST-segment elevation myocardial infarction, STEMI ST-segment elevation myocardial infarction, UA unstable angina
from onset to first PCI was 7.4 h overall, but was much shorter in the STEMI than in the NSTEMI group (2.8 vs. 21.8 h). Femoral access was more frequently chosen than radial access (86.6% vs. 8.6%, in 4.7% not reported). Stents were reported in 79.8% of patients overall.
(9.2%), treadmill exercise in 48 patients (7.6%), angio-computed tomography in eight patients (1.3%), stress echocardiography in ten patients (1.6%), nuclear imaging in four patients (0.6%), and other examinations in 141 patients (22.4%).
Diagnostic procedures
Cardiovascular medication including antiplatelets
Diagnostic procedures were done before revascularization. They involved echocardiography in 541 patients (86.0%), magnetic resonance imaging in 58 patients
Statins, beta-blockers, and ACE inhibitors/ARBs, all of which are recommended for secondary prevention in ACS patients, were administered in over 90% of
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patients during hospitalization and at discharge (. Tab. 4). Use of acetylic salicylic acid (ASA) was reported in 95.6% vs. 96.1%, clopidogrel in 60.8% vs. 73.0%, prasugrel in 45.6% vs. 22.5%, and any GP IIb/IIIa inhibitor in 52.4% vs. 18.9% of STEMI vs. NSTEMI patients, respectively. A summary of the use of antiplatelet combinations during hospital stay is provided in . Fig. 1 and in . Tab. 4 and . Tab. 5. Any dual combination of ASA+ (clopidogrel/prasugrel) was used in 94.0% vs. 91.0% of STEMI vs. NSTEMI patients, respectively.
20
0
40
60
80
Total NSTEMI STEMI
64.7
ASA + Clopidogrel
100 %
70.6 58.1
32.1
ASA + Prasugrel
21.9 43.6
Discussion
92.0 91.0
Dual antiplatelet
94.0
32.1 16.8
Dual antiplatelet + GPIIb/IIIa
49.3
Fig. 1 8 Combinations of antiplatelet drugs during hospital stay. Antiplatelets: acetylic salicylic acid (ASA), clopidogrel, prasugrel, ticlopidine, or GP IIb/IIIa inhibitors. ACS acute coronary syndrome, NSTEMI non-ST-segment elevation myocardial infarction, STEMI ST-segment elevation myocardial infarction 0 Myocardial Infarction
1 0.3
Cardiogenic Shock
2
4
6
7
8 %
Total NSTEMI-ACS STEMI-ACS
1.4
0.6
1.3 2.0 1.9 2.1
1.7 1.3
Recurrent Ischemia
1.8
0.7 0.5 0.0
0.9 5.1
Bleeding Heart Failure
1.5
1.4
2.7
2.7
Sustained Ventricular Tachycardia
2.4 0.6
6.1
3.4
4.9
Atrial Fibrillation/Flutter
5.6
2.4 2.1
Dyspnea Other Causes*
High-Degree AV Block
5
0.8
Cardiac Arrest/VF
Stroke
3
6.9
3.0 3.7
1.6 2.7
Fig. 2 8 In-hospital outcomes of acute coronary syndrome (ACS) survivors. *Dyspnea not due to heart failure or cardiogenic shock. ACS acute coronary syndrome, NSTEMI non-ST-segment elevation myocardial infarction, STEMI ST-segment elevation myocardial infarction, VF ventricular fibrillation
Complications During hospitalization, recurrent ischemia was reported in 1.3%, recurrent myocardial infarction in 0.8%, cardiogen-
on 19 patients (3.0%; STEMI 2.7% vs. NSTEMI 3.3%), and cardiac surgery on 18 patients (2.9%; STEMI 1.4% vs. NSTEMI 1.8%). Hemorrhagic complications during hospitalization occurred in 35 cases (5.6%), and eight of these cases were nonminimal (. Tab. 6). Blood transfusions were required in 14 patients, and surgical vessel repair in three cases.
ic shock in 1.3%, and cardiac arrest in 1.9% of patients (. Fig. 2). Resuscitation was performed on 24 patients (overall 3.8%; STEMI 4.7% vs. NSTEMI 3.0%), mechanical ventilation
This contemporary registry is a representative sample of patients with ACS surviving the hospital stay and indicates a high therapeutic standard considering guideline-adherent management prior to and during hospitalization for ACS. The time to first medical attention was short in STEMI and NSTEMI (53 vs. 96 min, respectively) patients, and is shorter than, for example, in the French FAST-MI 2010 survey (time to first call or contact STEMI 74 vs. NSTEMI 105 min). In line with the high prevalence of PCI centers in Germany, the great majority of hospitals initiated in-house specific therapy, and only 15.1% of patients needed transfer to other hospitals potentially resulting in delayed intervention. Antithrombotic and antiplatelet drugs have increasingly become the mainstay of ACS management in line with current guidelines, leading to substantially improved outcomes. Antithrombotic agents were initiated in the prehospital phase in 50.7% of STEMI and 33.3% of NSTEMI patients. During hospital stay, almost all patients received such drugs, with a high proportion of dual antiplatelet combination therapy, and with no major differences between STEMI and NSTEMI patients. One third (34.5%) of the STEMI patients received two to four antiplatelet agents and three to four anticoagulants, indicating a lot of switching during the hospital stay. Of note, in the latest guidelines, the highest level of evidence in the group of antithrombotic agents in NSTEMI-ACS patients was assigned to fondaparinux (IA), and in STEMI-ACS patients to bivalirudin (IB), while the uptake of the data in EPICOR (and other sources) was very low. Further, the rates of other cardiovascular drugs as recommended in the Herz 2014
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Original article Tab. 5 Anticoagulant and antiplatelet use Group
Number of antiplateletsa
Total (N=629) STEMI (N=296) NSTEMI (N=333)
0 1 2–4 0 1 2–4 0 1 2–4
Number of anticoagulantsb 0–1 2 (0.3%) 21 (3.3%) 13 (2.1%) 0 (0%) 4 (1.35%) 4 (1.35%) 2 (0.6%) 17 (5.11%) 9 (2.7%)
2 9 (1.4%) 125 (19.9%) 229 (36.4%) 2 (0.7%) 34 (11.5%) 88 (29.7%) 7 (2.1%) 91 (27.3%) 141 (42.3%)
3–4 4 (0.6%) 83 (13.2%) 143 (22.7%) 2 (0.7%) 60 (20.3%) 102 (34.5%) 2 (0.6%) 23 (6.9%) 41 (12.3%)
aASA, clopidogrel, prasugrel, ticlopidine, or GP IIb/IIIa inhibitorsbUnfractionated heparin, low-molecular-weight
heparin, fondaparinux, or bivalirudin
Tab. 6 In-hospital bleedingsa Hemorrhagic complications Related to a medical procedure Clinical significance – Minimal – Nonminimal Hemodynamic compromise – Minimal – Nonminimal Bleeding management – Blood transfusion – Red blood Urgent surgery Interruption of antithrombotic therapy
STEMI (N=296) n (%) 18 (6.1) 10 (55.6)
UA/NSTEMI (N=333) n (%) 17 (5.1) 10 (58.8)
Total (N=629) n (%) 35 (5.6) 20 (57.1)
13 (72.2) 5 (27.8)
14 (82.4) 3 (17.6)
27 (77.1) 8 (22.9)
15 (83.3) 3 (16.7)
16 (94.1) 1 (5.9)
31 (88.6) 4 (11.4)
9 (50.0) 9 (50.0) 0 (0.0) 2 (11.1)
5 (29.4) 5 (29.4) 3 (17.6) 2 (11.8)
14 (40.0) 14 (40.0) 3 (8.6) 4 (11.4)
NSTEMI non-ST-segment elevation myocardial infarction, STEMI ST-segment elevation myocardial infarction, UA unstable anginaaA subject could be reported in multiple categories
ACS guidelines (beta blockers, ACE inhibitors or angiotensin receptor blockers, statins) surpassed 90% each and were (e.g., compared with the GRACE results [20]) among the highest reported to date during hospital stay and at discharge. The high prescription rates of beta blockers in patients with UA/NSTEMI might indicate overtreatment, as the ESC guidelines recommend these drugs in patients with left ventricular dysfunction. In view of possible contraindications (e.g., no beta blockers in patients in Killip class ≥ III [2]), it seems difficult to increase the respective treatment rates further. Overall the performance measures as explicitly stipulated in the NSTEMI guidelines were fulfilled to a high degree [2]. In this EPICOR cohort, the proportion of patients with bleeding complications was considerably lower (5.6% over-
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all, 2.2% of patients requiring transfusion), despite the fact that a high rate of dual antiplatelet therapy (± GP IIb/IIIa inhibitors) was reported. In other registries, major bleeding was a relatively frequent and severe event: for example, in the ACTION-GWTG in an analysis of 90,000 STEMI and NSTEMI patients, 10.7% had major bleeding during hospital stay [21]. The risk of major bleeding was increased by about 60% in patients with triple antiplatelet vs. dual therapy in an analysis of the GRACE registry [20]. Recent studies have identified major bleeding after PCI as an important predictor of increased mortality [22]. The great majority of patients received PCI (85.6%), while CABG (2.7%) and thrombolysis (4.6%) played only a minor role. This is in agreement with guideline recommendations for STEMI where prima-
ry angioplasty is superior to fibrinolysis if performed early [4], and for NSTEMI where invasive management is indicated in all patients except those at low risk [2]. Even in rural infarction networks, primary angioplasty has been reported to be feasible and efficient [23].
Conclusion Methodical considerations have to be taken into account when discussing the current data. The registry follows a naturalistic approach to avoid protocol-induced procedures or outcomes to achieve high external validity of the findings [19]. As participation in the study was on a voluntary basis, a “positive” selection of centers with interest in the topic and possibly over-average standards is likely [24], and centers with a low volume of ACS patients might be less inclined to participate [11]. As the inclusion period ended in March 2011, not all of the newer antithrombotic drugs mentioned in the ACS guidelines such as dabigatran were documented. Further, the registry did not capture data on ACS patients who died during their hospital stay (usually older and sicker patients), which impacts survival rates. Lastly, the present cohort was rather small and thus subject to various unaccounted confounders typical for such an analysis.
Corresponding address Prof. Dr. U. Zeymer Klinikum Ludwigshafen Bremser Str. 79, 67063 Ludwigshafen Germany [email protected]
Acknowledgments. The study was financially supported by Astra Zeneca.
Compliance with ethical guidelines Conflict of interest. U. Zeymer, H. Heuer, P. Schwimmbeck, S. Genth-Zotz, K. Wolff, and C.A. Nienaber state that there are no conflicts of interest. All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.
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