Very Early veRsus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes

Conditions

Coronary Artery Disease

Keywords

Coronary Stenosis, Coronary Artery Disease, Acute coronary syndrome, Percutaneous Coronary Intervention, Multidetector Computed Tomography

Brief summary

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: * Very early invasive coronary investigation improves clinical outcome in patients with UAP/NSTEMI-ACS * CCTA performed before invasive coronary investigation will improve clinical management of patients with UAP/NSTEMI-ACS

Detailed description

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.

Jawad H. Butt, Klaus F. Kofoed, Henning Kelbæk, Peter R. Hansen, Christian Torp‐Pedersen et al. (18 authors)

Journal of the American Heart Association2021-09-2914 citations

10.1161/jaha.121.022333

Prognostic Value of Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

Kofoed KF, Engstrøm T, Sigvardsen PE, Linde JJ, Torp-Pedersen C, de Knegt M, Hansen PR, Fritz-Hansen T, Bech J, Heitmann M, Nielsen OW, Høfsten D, Kühl JT, Raymond IE, Kristiansen OP, Svendsen IH, Domínguez Vall-Lamora MH, Kragelund C, Hove JD, Jørgensen T, Fornitz GG, Steffensen R, Jurlander B, Abdulla J, Lyngbæk S, Elming H, Therkelsen SK, Jørgensen E, Kløvgaard L, Bang LE, Helqvist S, Galatius S, Pedersen F, Abildgaard U, Clemmensen P, Saunamäki K, Holmvang L, Gislason G, Kelbæk H, Køber LV.

2021-03-0135 citations

10.1016/j.jacc.2020.12.037

Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

Linde JJ, Kelbæk H, Hansen TF, Sigvardsen PE, Torp-Pedersen C, Bech J, Heitmann M, Nielsen OW, Høfsten D, Kühl JT, Raymond IE, Kristiansen OP, Svendsen IH, Vall-Lamora MHD, Kragelund C, de Knegt M, Hove JD, Jørgensen T, Fornitz GG, Steffensen R, Jurlander B, Abdulla J, Lyngbæk S, Elming H, Therkelsen SK, Jørgensen E, Kløvgaard L, Bang LE, Hansen PR, Helqvist S, Galatius S, Pedersen F, Abildgaard U, Clemmensen P, Saunamäki K, Holmvang L, Engstrøm T, Gislason G, Køber LV, Kofoed KF.

2020-02-01135 citations

10.1016/j.jacc.2019.12.012

86Coronary CT angiography as the first-line diagnostic strategy in patients with non-ST-segment Elevation Acute Coronary Syndrome - The VERDICT trial

Klaus F. Kofoed, Henning Kelbæk, Per Ejlstrup Sigvardsen, Christian Torp‐Pedersen, Peter RiisHansen et al. (12 authors)

European Heart Journal2019-10-01

10.1093/eurheartj/ehz747.0016

3335First-line coronary computed tomography predicts long-term clinical outcome in patients with Non-ST-segment elevation acute coronary syndrome - The VERDICT trial

Klaus F. Kofoed, Thomas Engstroem, Per Ejlstrup Sigvardsen, Christian Torp‐Pedersen, Jesper J. Linde et al. (12 authors)

European Heart Journal2019-10-01

10.1093/eurheartj/ehz745.0087

Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome

Klaus F. Kofoed, Henning Kelbæk, Peter Riis Hansen, Christian Torp‐Pedersen, Dan Eik Høfsten et al. (38 authors)

Circulation2018-12-10261 citations

10.1161/circulationaha.118.037152

Interventions

PROCEDUREInvasive coronary evaluation (Deferred)

Invasive coronary angiography and revascularization (PCI/CABG)

PROCEDUREInvasive coronary evaluation (Acute)

Invasive coronary angiography and revascularization (PCI/CABG)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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. * Age\> 18 years * At least one of the following: * ECG abnormalities suggestive of myocardial ischemia (newly developed ST segment depression, horizontal or descending \>= 0,05mV in two anatomically adjacent leads and/or T-wave inversion \>0,01 mV in two leads with prominent R wave or R/S ratio \>1 * Elevated myocardial ischemia biomarkers (Troponin, CK-MB)

Exclusion criteria

* Pregnancy * Circumstances preventing the patient from reading and/or understanding the research protocol information * Clinical indication for acute invasive coronary angiography - severe chest pain despite intravenous nitroglycerin infusion or hemodynamic instability * Expected survival of less than 1 year * Known allergy/hypersensitivity of pharmacological platelet inhibitors and/or iodine contrast that cannot be prevented medically Patients with known eGFR below 60 ml/min will not undergo CCTA, whereas patients in dialysis will undergo the entire study protocol

Design outcomes

Primary

Measure	Time frame	Description
Composite clinical endpoint	3 years	Composite endpoint of all cause mortality, non-fatal recurrent acute myocardial infarction, hospitalisation for refractory ischemia (acute coronary syndrome) or heart failure

Secondary

Measure	Time frame	Description
Non-fatal acute myocardial infarction	3 and 5 years	—
Repeat coronary revascularization	3 and 5 years	Recorded from 30 days post-index procedure
Hospital admittance due to left ventricular heart failure	3 and 5 years	—
GRACE Risk Score	3 and 5 years	All primary and secondary endpoints stratified by GRACE score at a threshold of 140
Bleeding	During index hospitalization - an expected average of 5 days	Major and minor bleeding according to TIMI and BARC classification systems
Non-bleeding, invasive procedure related complications	During index hospitalization - an expected average of 5 days	Invasive procedure related acute myocardial infarction, embolic stroke, cardiac arrest
Death	3 and 5 years	All-cause death
Hospital admittance due to refractory myocardial ischemia (acute coronary syndrome)	3 and 5 years	—

Other

Measure	Time frame	Description
CCTA prediction of clinical outcome	3 and 5 years	Clinical prognostic value of coronary pathology, cardiac and non-cardiac pathology identified by CCTA
CCTA guided treatment strategy	Within 30 days after performed CCTA and ICA	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.
CCTA diagnostic accuracy	Within 30 days after performed CCTA and ICA	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

Countries

Denmark

Outcome results

None listed