FFR-Guided PCI vs Medical Therapy in Stable Coronary Artery Disease
Abstract & Commentary
By Andrew J. Boyle, MBBS, PhD
Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco
Dr. Boyle reports no financial relationships relevant to this field of study.
Source: De Bruyne B, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med 2012;367:991-1001.
In patients with stable coronary artery disease (CAD), medical therapy is the mainstay of treatment. Percutaneous coronary intervention (PCI) guided by angiographic stenosis is more effective than medical therapy at reducing angina, but does not change the rate of death or myocardial infarction (MI). The potential benefit of PCI appears to depend on the extent of myocardial ischemia that is relieved by that revascularization. Fractional flow reserve (FFR), using a pressure-sensing guidewire in the cardiac catheterization laboratory, can determine the physiologic significance of a coronary artery stenosis in producing ischemia. Recent studies have shown that FFR-guided PCI is safer and more effective in guiding PCI than angiography alone. Whether FFR-guided PCI can improve clinical outcomes over medical therapy alone is not known. In the Fractional Flow Reserve vs Angiography for Multivessel Evaluation 2 (FAME 2) trial, De Bruyne and colleagues tested the hypothesis that FFR-guided PCI in stable CAD would improve outcomes over medical therapy alone.
They enrolled patients with stable CAD who were being considered for PCI, and performed FFR on all coronary stenoses. If there were one or more significant coronary stenoses (FFR ≤ 0.80), the patients were randomized to FFR-guided PCI of the significant lesions plus the best available medical therapy (PCI group) or to the best available medical therapy alone (medical therapy group). Patients with no significant stenoses (FFR > 0.80 in all vessels) were enrolled in a registry and received the best available medical therapy. All patients were prescribed aspirin, metoprolol, ACE inhibitors (or angiotensin receptor blocker if intolerant), and a high potency statin ± ezetimibe aiming for an LDL of < 70 mg/dL. Those who underwent PCI received a loading dose of clopidogrel 600 mg and then 75 mg daily for 12 months, and all received second-generation drug-eluting stents (DES). The primary endpoint was a composite of death, MI, or urgent admission for revascularization.
The baseline characteristics were well matched between groups. The mean age was 64 years, three-quarters were male, and 27% had diabetes. Approximately 11% were asymptomatic and 18%, 45%, 18%, and 6% had angina in Canadian cardiovascular society (CCS) classes I, II, III, and IV, respectively. The study was halted prematurely by the data safety and monitoring board after enrollment of 1220 patients (n = 447 randomized to PCI, n = 441 randomized to medical therapy, and n = 332 patients enrolled in the registry) because of a highly significant difference between groups with respect to the primary endpoint (4.3% in the PCI group vs 12.7% in the medical group; P < 0.001). There was no difference in the rate of death or MI between the PCI and medical therapy groups. The difference in the composite primary endpoint was driven by a lower rate of urgent revascularization in the PCI group (1.6% vs 11.1%; hazard ratio [HR] 0.13, P < 0.001). Interestingly, the rates of death from MI and urgent revascularization were similar between the PCI group and those in the registry who had no significant stenoses at all. The authors conclude that in patients with stable CAD and functionally significant stenoses, FFR-guided PCI plus the best available medical therapy, as compared with the best available medical therapy alone, decreased the need for urgent revascularization. In patients without ischemia, the outcome appeared to be favorable with the best available medical therapy alone.
This study tested a strategy of treating ischemia-producing lesions with PCI plus medical therapy vs medical therapy alone and showed that PCI results in fewer urgent hospital admissions requiring revascularization. Previous studies have tested PCI vs medical therapy based on angiographic guidance, which may overestimate the functional significance of coronary lesions. This study adds to the growing body of literature that treating ischemia, rather than angiographic stenoses, should be our goal because it results in better outcomes. In addition, this trial used second-generation DES in all patients, whereas prior studies, such as the COURAGE trial, used predominantly bare-metal stents. These differences in trial design may contribute to the benefits of PCI over medical therapy alone.
Several limitations of the study should be noted. First, the data safety and monitoring board stopped the trial prematurely because the primary endpoint was reached in favor of PCI over medical therapy. The study was therefore effectively underpowered to determine any difference in MI or death; there was only a difference in the rate of urgent revascularization, and the follow-up period was very short (mean 7 months). Unfortunately, this leaves us with an incomplete dataset. How much importance should we place on the endpoint of urgent revascularization? The patients who had urgent revascularization were all admitted to the hospital and nearly half of these had elevated biomarkers, ECG changes, or both. Considering that there were eight times more of these in the medical therapy group than the PCI group, I think this is an endpoint worth taking into account. Second, clopidogrel was given to all patients in the PCI group, but was left to the physicians’ discretion in the medical therapy group. Prior studies have not shown significant benefit of dual antiplatelet therapy in patients with stable CAD, but it is possible there may have been some benefit in this trial. Third, we are not told of the cost-effectiveness of PCI vs medical therapy. There will likely be several follow-up manuscripts. The longer-term results of the FAME 2 trial are eagerly awaited.