N Engl J Med 2024;390:1481-1492
Background: In patients with ST-elevation myocardial infarction (STEMI), opening the culprit artery improves outcomes. Nearly half of STEMI patients have disease in other coronary arteries. Whether revascularizing these non-culprit arteries improves outcomes remained uncertain. The PRAMI trial showed improvement in outcomes with complete revascularization but was relatively small, included 465 patients, and did not require the use of fractional flow reserve (FFR).
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The FFR-Guidance for Complete Nonculprit Revascularization (FULL REVASC) trial sought to assess if FFR-guided completed revascularization improves outcomes compared to culprit-only percutaneous coronary intervention (PCI).
The COMPLETE trial was not published by the time the FULL REVASC trial started enrolling patients.
Patients: Eligible patients had STEMI and were undergoing PCI or had high risk NSETMI undergoing urgent PCI. High risk NSTEMI included patients with dynamic ST–T-wave changes, ongoing chest pain, acute heart failure, hemodynamic instability independent of electrocardiographic changes, or life-threatening ventricular arrhythmias.
Eligible patients had to have multivessel coronary artery disease, defined as one or more lesions in a nonculprit artery with a diameter of ≥ 2.5 mm and a visually graded stenosis of 50 - 99%.
Patients were excluded if they had previous CABG, left main disease or cardiogenic shock.
Baseline characteristics: The trial randomized 1,542 patients – 778 randomized to culprit-only PCI and 764 randomized to complete revascularization. Patients were recruited from 32 centers in 7 countries.
Approximately 91% of the patients had STEMI and 9% had high risk NSTEMI.
The average age of patients was 65 years and 76% were men. Approximately 51% had hypertension, 16% had diabetes, 23% were on treatment for hyperlipidemia, 8% had prior myocardial infarction, and 35% were current smokers.
The number of residual coronary arteries with stenosis of 50-99% was 1 in 72% of the patients and 2 or more in the rest.
Procedures: Patients were randomly assigned in a 1:1 ratio to undergo culprit-only PCI or FFR-guide complete revascularization. The study was open label.
Patients in the culprit-PCI only group did not receive further revascularization during the index hospitalization. Patients in the FFR-guided complete revascularization could receive further revascularization during the index procedure or during the index hospitalization. PCI of non-culprit lesion was recommended if FFR was 0.80 or less.
Endpoints: The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The main secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization
Analysis was performed based on the intention-to-treat principle. The estimated sample size to achieve 80% with a two-sided alpha of 0.05 was 4,052 patients. This sample size would detect 0.75 risk ratio for the composite outcome of death or myocardial infarction at 1-year assuming 9.9% event rate in the culprit-only PCI. After the publication of the COMPLETE trial, the trial was stopped early due to ethical and feasibility concerns. Consequently, the original key secondary outcome (death from any cause, myocardial infarction, or unplanned revascularization) became the new primary outcome, and events after 1 year of follow-up were included in the primary analysis.
Results: The trial was stopped after randomizing 38.1% of the original sample size. Among the patients assigned to the FFR-guided complete-revascularization arm, the procedure was followed in 95.9% of the patients, and among these patients, 17.9% underwent FFR-guided complete revascularization of non-culprit lesions during the primary PCI and the rest during the index hospitalization. Among the patients assigned to culprit-only arm, the assigned strategy was followed in 99.6% of the patients. The median follow-up time was 4.8 years.
FFR was 0.8 or less in 392 (47.3%) of non-culprit vessels assessed, and PCI was performed in 369 (94.1%) of these vessels. In total, PCI was performed in 18.8% of the total non-culprit vessels. The average number of stents during the index hospitalization was 1 in the culprit-only PCI group and 2 in the complete revascularization group.
The primary composite outcome was not significantly different between both treatment groups (19.0% with complete-revascularization vs 20.4% with culprit-only PCI, HR: 0.93, 95% CI: 0.74 - 1.17; p= 0.53). There were also no significant differences in composite endpoint of death from any cause or myocardial infarction (16.5% with complete revascularization vs 15.3% with culprit-only PCI) or unplanned revascularization (9.2% with complete revascularization vs 11.7% with culprit-only PCI).
Stent thrombosis and stent restenosis were significantly more frequent in the complete revascularization arm (2.5% vs 0.9%, HR: 2.80, 95% CI: 1.18 – 6.67) and (4.2% vs 2.3%, HR: 1.84, 95% CI: 1.03 – 3.28), respectively.
Baseline risk or coronary anatomy did not significantly affect subgroup interactions for the primary outcome.
Conclusion: In patients with STEMI or high risk NSTEMI, FFR-guided complete revascularization compared to culprit-only PCI, did not improve the outcomes of death from any cause, myocardial infarction, or unplanned revascularization, over a median follow up time of 4.8 years. Complete revascularization resulted in more stent thrombosis and stent restenosis.
The study lost some statistical power by stopping early, resulting in a final power of 74%. We disagree with the authors' decision to halt the trial prematurely based on the findings of the COMPLETE trial. COMPLETE was the first large trial to demonstrate a benefit in hard outcomes when revascularizing stable plaques, and its results warrant further confirmation. Furthermore, COMPLETE used different strategy as FFR was not required.
Note to readers: Power measures the study’s ability to avoid a Type II error (false negative) and it equals 1 - β with β being the probability of a Type II error. In other words, power represents the probability of correctly rejecting the null hypothesis (H₀) when the alternative hypothesis (H₁) is true. Most clinical trials aim for 80% or 90% power. For example, a study with 80% power has a 20% risk of failing to detect a real effect.
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