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| ID | Type | Description | Link |
|---|---|---|---|
| EDITORS | Other Identifier | The Danish Council for Strategic Research (09-066994) |
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| Name | Class |
|---|---|
| University Hospital, Gentofte, Copenhagen | OTHER |
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The aim of this study is to evaluate if acute invasive coronary evaluation and treatment conducted within 12 hours of diagnosis improves clinical outcome compared to a deferred, subacute strategy in patients with unstable angina pectoris (UAP) / non-ST segment elevation myocardial infarction (NSTEMI) Acute coronary syndrome (ACS) Furthermore, in an observational design the potential clinical benefit of coronary computed tomography angiography (CCTA) to select patients for invasive investigation and treatment in the two treatment arms (acute vs deferred) is evaluated.
The following main hypothesis will be tested:
MATERIAL Consecutive patients suspected of UAP/NSTEMI will be screened for participation in the study. Only patients deemed clinically suited for invasive coronary evaluation and treatment will be included. A total of 2500 patients will be included in the trial at Departments of Cardiology of Danish Hospitals.
METHODS If the patients accept participation in the trial a computerized 1:1 randomization for acute invasive coronary evaluation (Intervention group - within 12 hours from time of diagnosis) or for deferred invasive evaluation (Control group - no later than 72 hours from time of diagnosis). All included patients undergo CCTA prior to invasive coronary evaluation, except for patient with moderately reduced renal function (se below). The treating invasive cardiologist will remain blinded to observational CCTA data. Patients with endstage renal disease in dialysis may undergo CCTA. CCTA data recorded as part of the research protocol will not be made available for the treating physician.
SECONDARY EXCLUSION Based on post-hoc expert clinical evaluation patients not having UAP/NSTEMI-ACS (arrythmias, pulmonary oedema, missed STEMI, pneumonia, Pulmonary emboli) will be excluded from analysis of difference between outcome measures in treatment strategy groups.
STATISTICAL METHODS Patients with UAP/NSTEMI-ACS are based on previous studies expected to have an event rate of 15% within 1 year and 50% at 4 years of the primary combined endpoint: all cause mortality, non-fatal recurrent myocardial infarction, hospitalisation for refractory ischemia or heart failure. In order to demonstrate a reduction of 25% within 3 years 711 patients in each group are needed. The study is powered to detect a clinical relevant reduction in mortality or heart failure hospitalization with a total of 2500 patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Deferred invasive evaluation | Active Comparator | Deferred invasive coronary evaluation and revascularization (PCI/CABG) within 72 hours from time of clinical diagnosis (CONTROL group) |
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| Very early invasive evaluation | Experimental | Acute invasive coronary evaluation within 12 hours from time of diagnosis - INTERVENTION group |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Invasive coronary evaluation (Deferred) | Procedure | Invasive coronary angiography and revascularization (PCI/CABG) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Composite clinical endpoint | Composite endpoint of all cause mortality, non-fatal recurrent acute myocardial infarction, hospitalisation for refractory ischemia (acute coronary syndrome) or heart failure | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Bleeding | Major and minor bleeding according to TIMI and BARC classification systems | During index hospitalization - an expected average of 5 days |
| Non-bleeding, invasive procedure related complications |
| Measure | Description | Time Frame |
|---|---|---|
| CCTA diagnostic accuracy | Determinants of diagnostic accuracy of CCTA for the identification of >50% and >70% coronary artery stenosis by invasive coronary angiography in both treatment strategy groups | Within 30 days after performed CCTA and ICA |
| CCTA guided treatment strategy |
Inclusion Criteria:
Patients with clinical suspicion of of UAP/NSTEMI acute coronary syndrome deemed suitable for invasive evaluation and treatment will be included in the study.
Exclusion Criteria:
Patients with known eGFR below 60 ml/min will not undergo CCTA, whereas patients in dialysis will undergo the entire study protocol
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| Name | Affiliation | Role |
|---|---|---|
| Lars V Køber, MD, DmSc | Department of Cardiology, Rigshospitalet, The Heart Center, Capital Region of Copenhagen, University of Copenhagen, Denmark | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Cardiology and Radiology, Rigshospitalet, The Heart Center, Capital Region of Copenhagen, University of Copenhagen | Copenhagen | 2100 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23420234 | Background | Navarese EP, Gurbel PA, Andreotti F, Tantry U, Jeong YH, Kozinski M, Engstrom T, Di Pasquale G, Kochman W, Ardissino D, Kedhi E, Stone GW, Kubica J. Optimal timing of coronary invasive strategy in non-ST-segment elevation acute coronary syndromes: a systematic review and meta-analysis. Ann Intern Med. 2013 Feb 19;158(4):261-70. doi: 10.7326/0003-4819-158-4-201302190-00006. | |
| 19458363 |
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| Invasive coronary evaluation (Acute) | Procedure | Invasive coronary angiography and revascularization (PCI/CABG) |
|
Invasive procedure related acute myocardial infarction, embolic stroke, cardiac arrest
| During index hospitalization - an expected average of 5 days |
| Death | All-cause death | 3 and 5 years |
| Non-fatal acute myocardial infarction | 3 and 5 years |
| Hospital admittance due to refractory myocardial ischemia (acute coronary syndrome) | 3 and 5 years |
| Repeat coronary revascularization | Recorded from 30 days post-index procedure | 3 and 5 years |
| Hospital admittance due to left ventricular heart failure | 3 and 5 years |
| GRACE Risk Score | All primary and secondary endpoints stratified by GRACE score at a threshold of 140 | 3 and 5 years |
Prediction of clinical treatment strategy based on CCTA - and the potential value of CCTA guided triage in terms of optimized patient management. Evaluation will be performed blinded to ICA findings. |
| Within 30 days after performed CCTA and ICA |
| CCTA prediction of clinical outcome | Clinical prognostic value of coronary pathology, cardiac and non-cardiac pathology identified by CCTA | 3 and 5 years |
| Background |
| Mehta SR, Granger CB, Boden WE, Steg PG, Bassand JP, Faxon DP, Afzal R, Chrolavicius S, Jolly SS, Widimsky P, Avezum A, Rupprecht HJ, Zhu J, Col J, Natarajan MK, Horsman C, Fox KA, Yusuf S; TIMACS Investigators. Early versus delayed invasive intervention in acute coronary syndromes. N Engl J Med. 2009 May 21;360(21):2165-75. doi: 10.1056/NEJMoa0807986. |
| 21777748 | Background | Kristensen TS, Kofoed KF, Kuhl JT, Nielsen WB, Nielsen MB, Kelbaek H. Prognostic implications of nonobstructive coronary plaques in patients with non-ST-segment elevation myocardial infarction: a multidetector computed tomography study. J Am Coll Cardiol. 2011 Jul 26;58(5):502-9. doi: 10.1016/j.jacc.2011.01.058. |
| 36351794 | Derived | Ratcovich H, Sadjadieh G, Linde JJ, Joshi FR, Kelbaek H, Kofoed KF, Kober L, Hansen PR, Torp-Pedersen C, Elming H, Gislason GH, Hofsten DE, Engstrom T, Holmvang L. Coronary CT and timing of invasive coronary angiography in patients >/=75 years old with non-ST segment elevation acute coronary syndromes. Heart. 2023 Feb 23;109(6):457-463. doi: 10.1136/heartjnl-2022-321640. |
| 34585591 | Derived | Butt JH, Kofoed KF, Kelbaek H, Hansen PR, Torp-Pedersen C, Hofsten D, Holmvang L, Pedersen F, Bang LE, Sigvardsen PE, Clemmensen P, Linde JJ, Heitmann M, Hove JD, Abdulla J, Gislason G, Engstrom T, Kober L. Importance of Risk Assessment in Timing of Invasive Coronary Evaluation and Treatment of Patients With Non-ST-Segment-Elevation Acute Coronary Syndrome: Insights From the VERDICT Trial. J Am Heart Assoc. 2021 Oct 5;10(19):e022333. doi: 10.1161/JAHA.121.022333. Epub 2021 Sep 29. |
| 33632478 | Derived | Kofoed KF, Engstrom T, Sigvardsen PE, Linde JJ, Torp-Pedersen C, de Knegt M, Hansen PR, Fritz-Hansen T, Bech J, Heitmann M, Nielsen OW, Hofsten D, Kuhl JT, Raymond IE, Kristiansen OP, Svendsen IH, Dominguez Vall-Lamora MH, Kragelund C, Hove JD, Jorgensen T, Fornitz GG, Steffensen R, Jurlander B, Abdulla J, Lyngbaek S, Elming H, Therkelsen SK, Jorgensen E, Klovgaard L, Bang LE, Helqvist S, Galatius S, Pedersen F, Abildgaard U, Clemmensen P, Saunamaki K, Holmvang L, Gislason G, Kelbaek H, Kober LV. Prognostic Value of Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes. J Am Coll Cardiol. 2021 Mar 2;77(8):1044-1052. doi: 10.1016/j.jacc.2020.12.037. |
| 32029126 | Derived | Linde JJ, Kelbaek H, Hansen TF, Sigvardsen PE, Torp-Pedersen C, Bech J, Heitmann M, Nielsen OW, Hofsten D, Kuhl JT, Raymond IE, Kristiansen OP, Svendsen IH, Vall-Lamora MHD, Kragelund C, de Knegt M, Hove JD, Jorgensen T, Fornitz GG, Steffensen R, Jurlander B, Abdulla J, Lyngbaek S, Elming H, Therkelsen SK, Jorgensen E, Klovgaard L, Bang LE, Hansen PR, Helqvist S, Galatius S, Pedersen F, Abildgaard U, Clemmensen P, Saunamaki K, Holmvang L, Engstrom T, Gislason G, Kober LV, Kofoed KF. Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome. J Am Coll Cardiol. 2020 Feb 11;75(5):453-463. doi: 10.1016/j.jacc.2019.12.012. |
| 30565996 | Derived | Kofoed KF, Kelbaek H, Hansen PR, Torp-Pedersen C, Hofsten D, Klovgaard L, Holmvang L, Helqvist S, Jorgensen E, Galatius S, Pedersen F, Bang L, Saunamaki K, Clemmensen P, Linde JJ, Heitmann M, Wendelboe Nielsen O, Raymond IE, Kristiansen OP, Svendsen IH, Bech J, Dominguez Vall-Lamora MH, Kragelund C, Hansen TF, Dahlgaard Hove J, Jorgensen T, Fornitz GG, Steffensen R, Jurlander B, Abdulla J, Lyngbaek S, Elming H, Therkelsen SK, Abildgaard U, Jensen JS, Gislason G, Kober LV, Engstrom T. Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome. Circulation. 2018 Dec 11;138(24):2741-2750. doi: 10.1161/CIRCULATIONAHA.118.037152. |
| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| D023921 | Coronary Stenosis |
| D054058 | Acute Coronary Syndrome |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
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