Paper: Kofoed KF et al. Prognostic Value of Coronary CT Angiography In Patients With Non-ST-Segment Elevation Acute Coronary Syndromes. JACC 2021. PMID: 33632478 [Access in Read by QxMD]
Clinical Question: Is CCTA equivalent to invasive coronary angiography (ICA) for risk assessment in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS)?
What They Did:
- Original RCT [2]:
- Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography (VERDICT) trial
- In the original VERDICT trial, 2100 patients with NSTEACS from 9 hospitals in Denmark were randomized to acute invasive strategy within 12h or deferred invasive strategy within 48 to 72h
- Primary Endpoint: Combination of all-cause death, nonfatal recurrent MI, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure
- Primary outcome occurred in 27.5% of in early ICA group vs 29.5% in the standard care group (not statistically significant)
- This data is from an observational component of the original VERDICT trial where all patients who were deemed eligible for early ICA received a blinded CCTA prior to ICA
- Severity of CAD defined as:
- Obstructive: ≥1 coronary with ≥50% stenosis
- Nonobstructive: <50% stenosis
- Extent of CAD defined as:
- High Risk: Obstructive LM or proximal LAD stenosis and/or multivessel disease
- Non-High Risk: All other patients
Outcomes:
- Primary: Composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure
Inclusion:
- ICA clinically indicated withing 12h from time of diagnosis
- Age ≥18 years
- Clinical suspicion of NSTEACS
- ≥1 of the following high-risk criteria:
- ECG changes indicating new ischemia (New ST segment depression, horizontal or down sloping ≥0.5mV in 2 consecutive leads, and/or T-wave inversion >0.01mV in 2 leads with prominent R-wave or R/S ratio >1)
- Increase in troponin levels
Exclusion:
- Pregnancy
- Inability to understand trial information
- Indication for acute ICA
- Expected survival <1 year
- Known intolerance to platelet inhibitors, heparin, or x-ray contrast
- For CCTA
- Previous CABG
- Plasma creatinine >150umol/L
- Known atrial fibrillation
- Women <45 years of age
Results:
- 978 patients had CCTA and angiography performed
- Median time interval between CCTA and ICA = 2h
- Median follow-up time = 4.2 years
- Primary Endpoint occurred in 208 patients (21.3%)
- CAD Severity:
- CCTA identified 73.4% of patients as having obstructive disease
- ICA identified 66.9% of patients as having obstructive disease
- CCTA and ICA were concordant in their findings in 88.5% of all patients
- Extent of CAD:
- CCTA identified 51% of patients as high risk
- ICA identified 36.8% of patients as high risk
- CCTA and ICA were concordant in their findings in 76.8% of all patients
- Obstructive disease and high-risk CAD were more commonly found in:
- Men who were slightly older
- Smokers
- Diabetics
- Previous history of PCI
- Ischemic ECG changes
- GRACE score >140 at clinical presentation
- Rate of primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with patients with nonobstructive CAD as defined by:
- CCTA (HR: 1.74; 95% CI 1.22 to 2.49; p = 0.002)
- Angiography (HR 1.54; 95% CI 1.13 to 2.11; p = 0.007)
- Among patients with nonobstructive CAD by CCTA, subsequent ICA did not identify patients at increased risk (HR 1.66; 95% CI 0.88 to 3.13; p = 0.117)
- In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non-high-risk CAD as defined by:
- CCTA (HR 1.56; 95% CI 1.18 to 2.07; p = 0.002)
- Angiography: HR 1.28; 95% CI 0.98 to 1.69; p = 0.07
- Among patients with non-high-risk CAD by CCTA, subsequent ICA did not identify patients at increased risk (HR 1.60; 95% CI 0.63 to 3.10; p = 0.167)
- Mortality Based on CAD Severity:
- CCTA Nonobstructive CAD: 7.7%
- ICA Nonobstructive CAD: 9.3%
- CCTA Obstructive CAD: 9.9%
- ICA Obstructive CAD: 9.3%
- Not statistically significant
- Mortality Based on Extent of CAD:
- CCTA Non-High-Risk CAD: 7.5%
- ICA Non-High-Risk CAD: 8.1%
- CCTA High-Risk CAD: 11.0%
- ICA High-Risk CAD: 11.4%
- Not statistically significant
Strengths:
- 1st study to compare the prognostic value of CCTA vs ICA in patients with NSTEACS
- Adjudication of events performed by an event committee blinded to coronary CTA and ICA findings and index management strategy
- In randomized part of the trial, there were no significant differences in CCTA diagnostic accuracy or in clinical outcomes between patients undergoing early vs standard treatment strategies
Limitations:
- Excluded patients with impaired renal function, known atrial fibrillation, previous CABG and women <45 years of age
- Functional assessment of coronary artery stenosis hemodynamic significance using invasive or noninvasive fractional flow reserve were not systematically conducted
- Primary outcome is a composite of non-equal outcomes. For example, death is not the same as hospital admission
- Selection bias: Only patients in whom cardiologist deemed that ICA was clinically indicated and logistically possible in 12hrs were included. This could bias results, but unclear exactly how
- Did not look at individual patient data on prognostication. What we really want to know is the individual patient at increased risk?
- If ICA is considered the gold standard, how many patients were ICA (+) but CCTA (-) and vice versa? HRs are not as helpful as sensitivity/specificity and LRs. Essentially this is a non-inferiority study, but the stats used are not helpful in advising the individual clinician what to do
Discussion:
- In this observational trial of CCTA vs ICA in patients with NSTEACS, CCTA was equivalent but not identical to ICA for assessment of long-term risk
- More obstructive CAD was found with CCTA compared to ICA. This could lead to more downstream testing and interventions
- Subsequent ICA in patients with nonobstructive CAD by CCTA or ICA did not provide further risk stratification
- CCTA is an anatomic study whereas ICA is not only an anatomic study but a functional study as well. This is important to understand because there may be some nonobstructive lesions seen on CCTA that are attributable to cardiovascular events from unstable plaques. Advantages of ICA include looking at coronary plaque morphology such as intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy looking at vascular calcification, plaque volume or high-risk plaque features all of which have prognostic implications
Author Conclusion: “Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS.”
Clinical Take Home Point: This multicenter observational substudy from the VERDICT trial shows that CCTA can identify severity and extent of CAD in an equivalent fashion to ICA in assessing long-term risk in patients with NSTEACS. HOWEVER, without individual patient data, evaluating false negatives, and false positives, statistically significant hazard ratios do not help guide us on what to do at the bedside. We should not be substituting CCTA for ICA based on this data.
References:
- Kofoed KF et al. Prognostic Value of Coronary CT Angiography I Patients With Non-ST-Segment Elevation Acute Coronary Syndromes. JACC 2021. PMID: 33632478
- Koefed KF et al. Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome. Circ 2018. PMID: 30565996
Post Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)
