Coronary Plaque Sealing: The DEFER Study and more... How Waiting Can Be Beneficial in Stable Coronary Artery Disease Patients ESC, Stockholm, 2005 M. Romanens, 21.09.2005 at www.kardiolab.ch
DEFER Study: Background 1. Based on paramount numbers of scientific papers, in patients with stable chest pain, the most important prognostic factor of a given coronary artery stenosis, is it s ability of inducing myocardial ischemia 2. In patients without ischemia, but with non flow limiting coronary leasons, which may be prone to rupture, plaque sealing using PTCA with or without drug eluting stents is an appealing concept to avoid future AMI in some minds. 3. The DEFER study tests this hypothesis in a randomized fashion. Further, patients without ischemia, regardless of the presence of chest pain, are not treated with PCI.
DEFER Study: Outcome Measures 1. Mean follow-up time 5 years 2. Occurence of Cardiac Death or non-fatal myocardial infarction (AMI) 3. Absence of chest pain
Patients scheduled for PCI no proof of ischemia N=325 Randomisation Defer PCI (N=167) Perform PCI (N=158) FFR 0.75 (N=91) FFR < 0.75 (N=76) FFR < 0.75 (N=68) FFR 0.75 (N=90) No PCI PCI PCI PCI DEFER N=91 REFERENCE N=144 PERFORM N=90
100 90 The DEFER Study: Diameter stenosis versus fractional flow reserve (FFS) Stenosis Severity (%) 80 70 60 50 40 30 20 Defer Perform Reference PFR 0.75 PFR < 0.75
Diagnostic Ability of Coronary Angiography to detect ischemia The DEFER Study 1 TP TN FP FN 106 72 109 38 SENS SPEZ PPV NPV ACC ALL 74 40 49 65 55 325 1 Reference is coronary stenosis of at least 50%
The DEFER Study: Cardiac Death and MI rate at 5 years p<0.03 % 20 p<0.005 15.7 15 10 p=0.20 7.9 5 3.3 % 0 Defer Perform Reference PFR 0.75 PFR < 0.75
The DEFER Study: Freedom of Chest Pain 100 80 60 ** p<0.01 ** * p<0.05 ** * ** ** 40 20 0 Baseline 1 month 1 year 2 years 5 years Defer Perform Reference
DEFER Study: Summary 1. In patients with stable chest pain, the most important prognostic factor of a given coronary artery stenosis, is it s ability of inducing myocardial ischemia (FFR < 0.75) 2. In those patients, clinical outcome of such ischemic stenosis, even when treated with PCI, is much worse than that of functionally non-significant stenosis. 3. The prognosis of non-ischemic stenosis (FFR > 0.75) is excellent and the risk of such non-significant stenosis or plaque to cause death and AMI is < 1% per year, and not decreased by stenting
Plaque Sealing: Overview 1. Untreated (aspirin, statin, ecc) mild coronary leasons have an annual risk for MACE of about 2% (CASS registry, natural course of the disease). 2. Risk reduction with preventive measures is around 80%, leading to a risk reduction from 2.0% to 0.4%. 3. The risk of sealed plaques is at least 1% for acute thrombosis even in the drug eluting stent aera.
Plaque Sealing: The Evidence 1. In 300 mild stenoses treated with PTCA, after 7 years only 2 sites were subsequently identified as the location of AMI 1 2. Mortality was not increased in over 3000 patients after successful ballon angioplasty during follow-up of 6 years 2 3. In 3812 patients with angina treated for single vessel disease with either mild (<50%), more severe (50-99%) or severe (100%) stenosis/occlusion, one year event rate of MACE was unacceptably high for stenoses < 50% (4.1% versus 0.7% in the DEFER study with FFE < 0.75) 3 1 Saito T, Date H, Taniguchi I, et al. Outcome of target sites escaping highgrade restenosis after percutaneous transluminal coronary angioplasty. Am J Cardiol 1999;83:857 61. 2 Weintraub WS, Ghazzal ZM, Douglas JS Jr, et al. Long-term clinical follow-up in patients with angiographic restudy after successful angioplasty. Circulation 1993;87:831 40. 3 Mercado N, Maier W, Boersma E, et al. Clinical and angiographic outcome of patients with mild coronary lesions treated with balloon angioplasty or coronary stenting. Implications for mechanical plaque sealing. Eur Heart J 2003;24:541 51.
Plaque Sealing: The Conclusions In spite of lack of scientific proof, plaque sealing by mechanical means is more important than plumbing in terms of prognosis of the patients, even though it can only be applied to a selection of stenoses and is far from being foolproof. A somewhat cynical statement by Spencer B King III, MD, on the occasion of a live angioplasty course in Atlanta, USA, on 29 May 2003 points in the same direction: How to decide whether or not to dilate a mild lesion? If you want to dilate it, do IVUS (intravascular ultrasound); if you don t, do the flow wire! 1 1 Plaque sealing by angioplasty. A Mini Symposium. B. Meier. Heart 2004; 90: 1395.1397
DEFER Study: Conclusion Stenting a non-ischemic stenosis does not benefit patients with stable chest pain, neither in prognostic nor symptomatic respect
Plaque Sealing: Conclusion Plaque sealing is a concept aiming at risk reduction for MACE. The only possible but unproven benefit is in comparison with the natural course of CAD. Plaque sealing may reduce MACE within the sealed plaque. Modern medical therapy seals all plaques within the coronary tree. Therefore, a human being is not a series of tubes, awaiting to be stented, and current evidence does strongly support the presence of excess risk for plaque sealing in comparison with medical treatment of CAD alone. Plaque sealing is in the mind of many interventionalists. They believe, that plaque sealing will save the lives of their patients. The evidence for plaque sealing in mild stenoses favors a non sealing approach, well known in medicine: First do not harm.