On-site computed tomography-derived fractional flow reserve to guide the management of patients with stable coronary artery disease: The TARGET randomized trial
Reported from ACC.23/WCC
Mirvat Alasnag provides her take on this clinical trial presented by Yundai Chen at the American College of Cardiology Scientific Session (ACC.23/WCC).
The current guidelines incorporated the use of FFR-CT (Computed tomography-determined Fractional flow reserve) in the 2021 edition. The objective of the TARGET Trial, which was presented as a late-breaking trial at ACC23 scientific sessions, is to determine whether a strategy of on-site machine learning (ML)-based FFR-CT would improve clinical and economic outcomes when compared with a stress test-based standard pathway in stable patients with intermediate stenosis by cardiac computed tomographic angiography (CCTA). Stable patients presenting with chest pain and a CCTA indicating stenosis of 30-90% were randomized to a standard-of-care group (Stress cardiac MRI, SPECT, exercise ECG) or on-site FFR-CT.
The main inclusion criteria included the following:
- Consecutive patients with new-onset chest pain suspicious of coronary artery disease (CAD).
- Subjects with intermediate-to-high pretest probability of CAD were recruited based on the CAD Consortium basic pretest probability score.
- CCTA result 30-90% diameter stenosis in at least one major coronary artery (coronary artery diameter ≥ 2.5 mm).
The main exclusion criteria are summarized below:
- Diagnosed or suspected acute coronary syndrome requiring hospitalization or emergent testing
- Hemodynamically or clinically unstable condition systolic blood pressure < 90 mmHg or serious atrial or ventricular arrhythmias
- Known CAD with prior myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or any angiographic evidence of ≥ 50% stenosis in any major coronary artery
- Patients with left main branch stenosis ≥ 50% or one major coronary stenosis > 90% by CCTA
- Known severe congenital, valvular (moderate and above), or cardiomyopathy process (hypertrophic cardiomyopathy or reduced systolic left ventricular function ≤ 40%) which could explain cardiac symptoms
- Unable to provide written informed consent or participate in long-term follow-up
Those in the standard group with a positive test would undergo invasive coronary angiography and those with an FFR-CT of < 0.8 would undergo invasive coronary angiography (ICA). The primary endpoint was the rate of ICA without obstructive CAD or intervention within 90 days. The secondary endpoint was Major adverse cardiovascular events (MACE), quality of life and medical expenditure within 1 year.
Of the 7683 patients screened, 1216 patients met the inclusion criteria with 608 assigned to each arm. Of those undergoing FFR-CT, 412 completed the test which yielded a positive result, 2 didn’t complete the test and 194 had a negative result. On ICA, 333 had obstructive CAD of whom 302 underwent revascularization (291 percutaneous and 11 bypass surgery) and 31 received guideline-directed medical therapy. The mean age was 59 years with men accounting for 65% of the total cohort. 23% were diabetic, 61% hyperlipidemic and 32% smokers.
Disappointingly, medical therapy fell short in the majority with 80-83% receiving antiplatelet therapy, 65% receiving statins and only 40% beta-blockers. The majority of patients had atypical or non-anginal chest pain (53% and 28% respectively). 61% had class 2 angina and 38% were reported to have class 3 angina. The majority of the standard care group underwent exercise stress test 88% and only 15% had SPECT and 9% had stress echo. All 3 coronary artery territories were noted to have ischemia with >50% occurring in the Left Anterior Descending artery territory. Invasive FFR was performed in a small portion of the patients (9-13%).
As compared with the standard group, the proportion of patients undergoing ICA without obstructive CAD or with obstructive CAD who did not undergo intervention within 90 days was significantly reduced in the FFR-CT group (28.3% [119/421] vs. 46.2% [223/483], P<0.001). This was mainly driven by a reduction in the proportion of patients found to have no-obstructive CAD in the FFR-CT group compared to the standard group (20.9% [88/421] vs. 38.0% [184/483]). Major adverse cardiovascular events (MACE) did not differ significantly in the FFR-CT group (hazard ratio, 0.88; P=0.8).
Variable | FFR-CT | Standard Care | P Value |
1 event | 48 (8.2) | 54 (9.2) | 0.55 |
Hospitalization for unstable angina | 39 (6.6) | 44 (7.5) | 0.58 |
Revascularization after 90 days | 7 (1.2) | 16 (2.7) | 0.06 |
Non-fatal MI | 7 (1.2) | 9 (1.5) | 0.62 |
Cardiovascular death | 2 (0.3) | 1 (0.2) | 0.62 |
Overall, ML-based FFR-CT performed well providing real-time results for a variety of anatomic coronary diseases. The standard care pathway in combination of CCTA and stress test led to a higher ICA rate than in the FFR-CT strategy. An on-site FFR-CT strategy can play an important role in the management of intermediate-risk patients with stable chest pain further consolidating the role of CCTA as a “gatekeeper”. Given that the majority of patients had atypical or non-cardiac chest pain with a mean age of 59 years suggests this was an overall low-risk population and its application in higher-risk patients with clinical events or left ventricular dysfunction remains unknown. Some of the other limitations include the variety of stress tests in the standard group rendering it difficult to conduct direct comparisons. There was no further analysis of the revascularization in particular whether it was complete or incomplete. Since this was conducted in China only, the quality of life and cost analyses may differ by geography. The efficiency and reliability of the onsite FFR-CT cannot be extrapolated to other centres with no experience.
In conclusion, in stable patients with intermediate (30%-90%) stenosis detected by CCTA, an on-site ML-based FFR-CT strategy is feasible, safe and effective. Compared with the standard care pathway, on-site FFR-CT reduced the proportion of patients with stable CAD undergoing ICA without obstructive disease or requiring intervention within 90 days. On-site FFR-CT strategy increased revascularization overall without improving quality of life or reducing major adverse cardiovascular events, although a trend towards a lower cost was observed.
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