Prevention Of Restenosis With Tranilast And Its Outcomes Research Articles

Machine Learning to Predict Stent Restenosis Based on Daily Demographic, Clinical, and Angiographic Characteristics

BackgroundMachine learning (ML) has arrived in medicine to deliver individually adapted medical care. This study sought to use ML to discriminate stent restenosis (SR) compared with existing predictive scores of SR. To develop an easily applicable model, we performed our predictions without any additional variables other than those obtained in daily practice. MethodsThe dataset, obtained from the Grupo de Análisis de la Cardiopatía Isquémica Aguda (GRACIA)-3 trial, consisted of 263 patients with demographic, clinical, and angiographic characteristics; 23 (9%) of them presented with SR at 12 months after stent implantation. A methodology to work with small imbalanced datasets, based in cross-validation and the precision/recall (PR) plots, was used, and state-of-the-art ML classifiers were trained. ResultsOur best performing model (0.46, area under the PR curve [AUC-PR]) was developed with an extremely randomized trees classifier, which showed better performance than chance alone (0.09 AUC-PR, corresponding to the 9% of patients presenting SR in our dataset) and 3 existing scores; Prevention of Restenosis With Tranilast and its Outcomes (PRESTO)-1 (0.31 AUC-PR), PRESTO-2 (0.27 AUC-PR), and Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) (0.18 AUC-PR). The most important variables ranked according to their contribution to the predictions were diabetes, ≥2 vessel-coronary disease, post-percutaneous coronary intervention thrombolysis in myocardial infarction (PCI TIMI)-flow, abnormal platelets, post-PCI thrombus, and abnormal cholesterol. To counteract the lack of external validation for our study, we deployed our ML algorithm in an open source calculator, in which the model would stratify patients of high and low risk as an example tool to determine generalizability of prediction models from small imbalanced sample size. ConclusionsApplied immediately after stent implantation, a ML model better differentiates those patients who will present with SR over current discriminators.

Guidelines for Critical Limb Ischaemia and Diabetic Foot – Introduction

The European Society for Vascular Surgery appoints Guidelines Committees to write clinical practice guidelines for vascular surgery. Guidelines for the care of patients with critical limb ischaemia accompany this commentary. Guideline development was recommended in 1990 by the Institute of Medicine, to improve decision-making for specific patient circumstances, and to decrease the variability between healthcare providers.1,2 Appropriate decision-making is critical to achieving excellent outcomes. Guidelines have become more popular in surgery and medicine. This probably results from increased attention to evidence-based medicine, the desire for reproducibility in the choice of treatment for a specific patient, increasing government legislation, the need to satisfy insurance regulations, and legal pressures. Critical limb ischaemia (CLI) is a complex condition and there is significant variability in clinical practice, although a valid evidence base is available to guide recommendations. The significant increase in the volume of scientific literature concerning critical limb ischaemia published in recent years along with the number of technical and medical advances supports guideline recommendations with more certainty than before. Potential increases in healthcare costs and risks due to industry and the public-driven use of novel treatments, makes the current guidelines increasingly important.3––6 Many clinical situations of patients with critical limb ischaemia have not been the subject of randomised clinical trials. Patient care, however, needs to be delivered and decisions have to be made in these situations. Therefore, this document should also provide guidance for decisions where extensive Level 1 evidence is not available, and recommendations are determined on the basis of the currently available best evidence. By providing information about the relevance and quality of evidence, this document will enable the reader to locate the most important and evidence-based information relevant to the individual patient.7 To optimise the implementation of the current guideline document, its length has been kept as short as possible to enable easy access to its information. This document is supposed to be a guide, not a set of rules, and allows flexibility for specific patient circumstances.

Geographical Differences in the Rates of Angiographic Restenosis and Ischemia-Driven Target Vessel Revascularization After Percutaneous Coronary Interventions: Results From the Prevention of Restenosis With Tranilast and its Outcomes (PRESTO) Trial

Geographical Differences in the Rates of Angiographic Restenosis and Ischemia-Driven Target Vessel Revascularization After Percutaneous Coronary Interventions: Results From the Prevention of Restenosis With Tranilast and its Outcomes (PRESTO) Trial

Geographical Differences in the Rates of Angiographic Restenosis and Ischemia-Driven Target Vessel Revascularization After Percutaneous Coronary Interventions: Results From the Prevention of Restenosis With Tranilast and its Outcomes (PRESTO) Trial

Geographical Differences in the Rates of Angiographic Restenosis and Ischemia-Driven Target Vessel Revascularization After Percutaneous Coronary Interventions: Results From the Prevention of Restenosis With Tranilast and its Outcomes (PRESTO) Trial Mandeep Singh, Brent A. Williams, Bernard J. Gersh, Robyn L. McClelland, Kalon K. L. Ho, James T. Willerson, William F. Penny, Donald E. Cutlip, David R. Holmes, Jr Many cardiologists consider it reasonable to assume in clinical practice that percutaneous coronary intervention using drug-eluting stents ought to be considered equivalent, if not superior, to bypass surgery. In the absence of a definitive clinical trial to support this view, how should the prudent, cutting-edge cardiologist proceed? This study assessed the geographical differences in target vessel revascularization (TVR) after percutaneous coronary intervention (PCI) in the Prevention of Restenosis With Tranilast and its Outcomes (PRESTO) trial. An aggressive approach to PCI is more common in the U.S. than in other countries. The impact of this approach on restenosis outcomes has not been studied. Using the PRESTO trial, we compared nine-month ischemic TVR after PCI in U.S.-treated patients (n = 5,026) with rates in other countries (n = 6,458). We defined TVR as repeat intervention for chest pain/positive stress test. Additionally, angiographic restenosis (≥50% narrowing or ≥50% loss of gain at nine-month follow-up) was compared between U.S. and non-U.S. patients within the prespecified angiographic subset (n = 2,823). Regression models were developed to adjust for clinical and lesion-related characteristics. Higher rates of TVR (18% vs. 11%), and angiographic restenosis (65% vs. 48%) were observed in patients treated in the U.S. as compared with the other patients (p < 0.01 for both comparisons). Patients treated in the U.S. were more likely to be female, diabetic, not currently smoking, to have unstable angina, and to have a prior PCI. In U.S. patients, lesions tended to be longer, but less likely to be American College of Cardiology/American Heart Association class C. After adjusting for clinical and angiographic variables, PCI in the U.S. was still associated with increased angiographic restenosis and ischemic TVR. Angiographic restenosis and ischemia-driven TVR rates were higher in patients treated in the U.S. The difference could only partially be explained by the higher prevalence of measured adverse clinical and angiographic features.

Nine-Month Outcome of Patients Treated by Percutaneous Coronary Interventions for Bifurcation Lesions in the Recent Era: A Report From the Prevention of Restenosis With Tranilast and Its Outcomes (PRESTO) Trial

Nine-Month Outcome of Patients Treated by Percutaneous Coronary Interventions for Bifurcation Lesions in the Recent Era: A Report From the Prevention of Restenosis With Tranilast and Its Outcomes (PRESTO) Trial

Outcome of Patients With Prior Percutaneous Revascularization Undergoing Repeat Coronary Intervention (from the PRESTO Trial)

Patients with previous percutaneous coronary intervention (PCI) are often excluded from clinical trials. As a result, limited data are available on the long-term outcome of such patients undergoing repeat PCI. In this study, we assessed the impact of previous PCI on outcomes in patients undergoing repeat PCI. We compared the baseline features and outcomes of 7,056 patients without previous PCI (group I) with those of 1,281 patients with previous PCI of the original target lesion (group II) and 1,408 patients with previous PCI of a nontarget lesion (group III) undergoing PCI in the Prevention of Restenosis with Tranilast and its Outcomes (PRESTO) trial. Compared with patients in group I, patients in groups II and III were more likely to have diabetes (25% and 24% vs 21%, p <0.02), previous myocardial infarction (51% and 56% vs 29%, p <0.001), and ostial lesions (10% and 7% vs 5%, p <0.001), and less likely to have, as their indication for PCI, myocardial infarction (2% and 7% vs 17%, p <0.001). At 1 month, major adverse cardiac events, including death, myocardial infarction, and repeat revascularization, were low and similar in all 3 groups. Compared with patients in group I, the risk of major adverse cardiac events at 9 months was significantly increased for patients in groups II (34.1% vs 18.6%, relative risk [RR] 2.03, adjusted RR 1.78, 95% confidence interval 1.58 to 2.01) and III (23.9% vs 18.6%, RR 1.30, adjusted RR 1.16, 95% confidence interval 1.02 to 1.33). The increased risk of major adverse cardiac events was entirely due to higher rates of repeat revascularization. In conclusion, despite similar short-term outcomes, patients with previous PCI undergoing PCI of either target or nontarget lesions had lower event-free survival at 9 months of follow-up.

Nine-Month Outcome of Patients Treated by Percutaneous Coronary Interventions for Bifurcation Lesions in the Recent Era: A Report From the Prevention of Restenosis With Tranilast and its Outcomes (PRESTO) Trial

The aim of this research was to determine the influence of bifurcation lesions on the outcome of patients undergoing percutaneous coronary intervention (PCI) in the recent era. The treatment of bifurcation lesions by PCI has been associated with an increased complication rate. Whether recent improvements of interventional practice have translated into improved outcomes in this patient subgroup is unknown. The 11,482 patients enrolled in the Prevention of Restenosis with Tranilast and its Outcomes (PRESTO) were stratified according to the presence (n = 1,412) or absence (n = 10,068) of at least one bifurcation lesion treated by PCI. Baseline characteristics and outcome of patients undergoing PCI for bifurcation lesions were compared to those of patients treated for nonbifurcation lesions. Patients treated for bifurcation lesions were less likely to have prior myocardial infarction (MI), prior coronary artery bypass graft surgery, and had a higher proportion of current stable angina (p < 0.01 for all comparisons). Bifurcation lesions involved more frequently the left anterior descending coronary artery and were more complex (angulated, eccentric, ostial, and tortuous) than nonbifurcation lesions. Percutaneous coronary intervention of bifurcation lesions was characterized by less frequent stent implantation (71% vs. 80%); PCI of bifurcation lesions was associated with an increased rate of combined end point death/MI/target vessel revascularization (TVR) at nine months (18% vs. 15%, p = 0.002) because of increased rates of TVR (17% vs. 14%, p < 0.001), whereas death (1%) and MI (1%) were not different between groups. Percutaneous coronary intervention of bifurcation lesions is associated with higher TVR at follow-up. However, the risk of death, MI, death/MI was similar in patients treated for bifurcation or nonbifurcation lesions.

Predictive factors for ischemic target vessel revascularization in the Prevention of Restenosis with Tranilast and its Outcomes (PRESTO) trial

The aim of the present study was to determine the rates of target vessel revascularization (TVR) and to determine predictors of TVR from clinical and angiographic variables available in the Prevention of Restenosis With Tranilast and its Outcomes (PRESTO) database. The rates of TVR after percutaneous revascularization procedures, and its prediction with available clinical and angiographic variables, is less well known. We studied nine-month TVR in 11,484 patients enrolled in the PRESTO trial. Clinical, lesion-related, and procedural characteristics were analyzed in a logistic regression model. Study data were divided at random into an 80% training set on which the models were developed and a 20% hold-out set on which the model properties were evaluated. A total of 14% (n = 1,609) had ischemic TVR. Clinical variables with increased risk for TVR included younger age; hypertension; diabetes mellitus; nonsmokers; unstable angina; previous coronary artery bypass grafting; peripheral vascular disease; procedure- and lesion-related such as ostial location, multilesion angioplasty, location in the left anterior descending artery, length > or =20 mm, in-stent restenosis at baseline, and use of rotablator. There was significant increase in the risk of ischemic TVR at U.S. treatment sites. Smoking and stent placement were associated with lower risk of ischemic TVR. The mean area (+/- SD) under the receiver-operating characteristic curve of the bootstrap samples was 0.66, indicating a modest ability of the model to discriminate patients who needed TVR on follow-up. Despite being the largest prospective trial designed to test restenosis, the discriminatory ability of the clinical and angiographic variables to predict TVR is modest.

Impact of mild or moderate chronic kidney disease on the frequency of restenosisResults from the PRESTO trial

The goal of this study was to determine if restenosis is increased in mild and moderate chronic kidney disease (CKD) patients after percutaneous coronary intervention (PCI). Mortality is increased in CKD after PCI. Restenosis may contribute to increased late mortality. We analyzed 11,187 patients with a creatinine &lt;1.8 mg/dl from the Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) trial, grouped by estimated creatinine clearance (CrCl) (&lt;60, 60 to 89, &gt;89 ml/min). The Cox proportional hazards models investigated the association between CrCl group and death, myocardial infarction, and target vessel revascularization (TVR). Generalized estimating equation regression models determined the association between CrCl group and lesion-specific restenosis. At 30 days, there was no difference in myocardial infarction, death, or TVR between the CrCl groups. At nine months, mortality was higher in the lowest CrCl group (2.2%, 1.2%, 0.8%; p &lt; 0.001), which was no longer significant after adjusting for confounding variables. Myocardial infarction and TVR were not different between the groups. In patients undergoing protocol follow-up angiography, restenosis (≥50%) was not increased with CKD (32%, 32%, 37%; p = 0.02). Mortality nine months after PCI is mildly increased in mild or moderate CKD patients. However, restenosis is not and does not account for the increased mortality.

Impact of mild or moderate chronic kidney disease on the frequency of restenosis: Results from the PRESTO trial

The goal of this study was to determine if restenosis is increased in mild and moderate chronic kidney disease (CKD) patients after percutaneous coronary intervention (PCI). Mortality is increased in CKD after PCI. Restenosis may contribute to increased late mortality. We analyzed 11,187 patients with a creatinine <1.8 mg/dl from the Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) trial, grouped by estimated creatinine clearance (CrCl) (<60, 60 to 89, >89 ml/min). The Cox proportional hazards models investigated the association between CrCl group and death, myocardial infarction, and target vessel revascularization (TVR). Generalized estimating equation regression models determined the association between CrCl group and lesion-specific restenosis. At 30 days, there was no difference in myocardial infarction, death, or TVR between the CrCl groups. At nine months, mortality was higher in the lowest CrCl group (2.2%, 1.2%, 0.8%; p < 0.001), which was no longer significant after adjusting for confounding variables. Myocardial infarction and TVR were not different between the groups. In patients undergoing protocol follow-up angiography, restenosis (>/=50%) was not increased with CKD (32%, 32%, 37%; p = 0.02). Mortality nine months after PCI is mildly increased in mild or moderate CKD patients. However, restenosis is not and does not account for the increased mortality.

Clinical and angiographic predictors of restenosis after percutaneous coronary intervention: Insights from the prevention of restenosis with tranilast and its outcomes (PRESTO) trial

Clinical and angiographic predictors of restenosis after percutaneous coronary intervention: Insights from the prevention of restenosis with tranilast and its outcomes (PRESTO) trial

Clinical and angiographic predictors of restenosis after percutaneous coronary intervention: insights from the Prevention of Restenosis With Tranilast and Its Outcomes (PRESTO) trial.

Restenosis prediction from published studies is hampered by inadequate sample size and incomplete angiographic follow-up. The prediction of restenosis with the existing variables is poor. The aim of the present study was to include the clinical and angiographic variables commonly associated with angiographic restenosis and develop a prediction model for restenosis from the PRESTO database. This study included 1312 patients with a single lesion enrolled in the angiographic substudy of the PRESTO trial. We constructed 2 risk scores. The first used preprocedural variables (female gender, vessel size [< or =2.5 mm, 2.5 to 3 mm, 3 to 3.5 mm, 3.5 to 4 mm, >4 mm], lesion length >20 mm, diabetes, smoking status, type C lesion, any previous percutaneous coronary intervention [PCI], and unstable angina) derived from previous studies. Estimated restenosis rates and corresponding variability for each possible level of the resultant risk score were obtained via bootstrapping techniques. The area under the receiver-operator characteristic (ROC) curve was 0.63, indicating modest discriminatory ability to predict restenosis. The second approach constructed a multiple logistic regression model considering significant univariate clinical and angiographic predictors of restenosis identified from the PRESTO database (treated diabetes mellitus, nonsmoker, vessel size, lesion length, American College of Cardiology/American Heart Association type C lesion, ostial location, and previous PCI). The area under the ROC curve for this risk score was also 0.63. The preprocedural clinical and angiographic variables from available studies and from the PRESTO trial have only modest predictive ability for restenosis after PCI.

Outcomes in patients with diabetes mellitus undergoing percutaneous coronary intervention in the current era: A report from the prevention of restenosis with tranilast and its outcomes (PRESTO) trial

Outcomes in patients with diabetes mellitus undergoing percutaneous coronary intervention in the current era: A report from the prevention of restenosis with tranilast and its outcomes (PRESTO) trial

PRESTO! No Change for Diabetics

Improved techniques in percutaneous intervention did not eliminate the consequences that affect diabetic patients undergoing such procedures in the Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) trial. The study, reported in this week’s issue of the journal Circulation ( Circulation . 2004;109:476–480), compared the outcomes of the 2694 diabetic patients and the 8798 nondiabetic patients in the multicenter trials. The PRESTO study itself, designed to evaluate the effect of tranilast on percutaneous intervention outcomes, found that the drug had no effect. In this secondary analysis, diabetic patients were older, were more likely to be female, had more congestive heart failure and hypertension, and were more likely to have undergone coronary artery bypass grafting and to have unstable angina. Their body mass index was higher than that of the nondiabetic patients, and they had a lower ejection fraction. Success rates of the procedures were similar between the two groups. Diabetes was independently associated with death at 9 months, an increased likelihood of target-vessel revascularization, and the composite end point of death/myocardial infarction and target-vessel revascularization. The authors wrote, “Despite advances in interventional techniques, diabetes remains a significant independent predictor of adverse events in the intermediate term after PCI [percutaneous intervention]. . . . There are multiple possible explanations for this observation, including the known impairment of fibrinolysis and increased platelet aggregability, which may contribute …

Results of prevention of REStenosis with tranilast and its outcomes (PRESTO) trial

Results of prevention of REStenosis with tranilast and its outcomes (PRESTO) trial

Late-Breaking Clinical Trials at the American Heart Association’s Scientific Sessions 2001

The PRoject of Ex-vivo Vein graft ENgineering via Transfection (PREVENT) II trial found that a double-stranded piece of DNA called the E2F duplex decoy significantly reduced failure of vein grafts after coronary artery bypass surgery (CABG), according to Eberhard Grube, MD, of the Heart Center in Sieburg, Germany, during the American Heart Association’s 2001 Scientific Sessions in Anaheim, Calif. During the Late-Breaking Clinical Trials Plenary Session on November 12, 2001, Dr Grube said that his decoy blocks vascular smooth muscle proliferation, which is the core problem in vein graft failure. Eberhard Grube, MD (photo by Paul C. SoRelle) The graft is treated during CABG after the vein has been removed from the leg. A solution containing the E2F decoy is placed in a tube with a stopcock on one side and a syringe at the other, which is used to apply pressure. The vein is placed in the tube and pressure is applied via the syringe to ≈6 lbs/in2 for 10 minutes, Dr Grube said. That is enough to insure that 80% of the cells in the graft will take up the decoy. The transfected graft then is used to bypass blocked coronary arteries. In the study, 101 patients who had undergone CABG were randomly assigned to the treatment group, and 99 were assigned to placebo. In angiographic studies performed on 61 placebo patients and 75 treated patients who received a total of 309 grafts, the E2F decoy was associated with a 30% relative reduction in a composite index of vein graft failure and death, said Dr Grube. In addition, there was a 30% reduction in the size of vessel wall volume. According to Dr Grube, the results are similar to those in the PREVENT I trial, which used E2F to treat bypass veins in peripheral artery disease. He …

Living the Dream of No Restenosis

“If I am in a dream, please don’t wake me” are the now-fabled words spoken by Patrick Serruys while viewing follow-up intravascular ultrasound images of sirolimus-eluting stents. The dream of an effective treatment for restenosis has eluded decades of effort by an army of investigators. Scores of devices, hundreds of drugs, and innumerable revascularization “strategies” have failed to eliminate the 10% to 50% risk of recurrence after angioplasty. The wasteland of failed anti-restenosis trials was expanded this summer by the 11 500-patient, hundred million dollar, mega-trial Prevention of REstenosis with Tranilast and its Outcomes (PRESTO), which demonstrated that tranilast (a cytokine inhibitor showing superb results in smaller pilot studies) was no better than placebo. When you take out a gallbladder, it doesn’t grow back. Yet, no matter how much skill, experience, time, and effort the interventionist brings to the table, restenosis can entirely reverse a perfect procedural result within months. Until now, only the efficacy provided by vascular brachytherapy has offered hope to patients with in-stent restenosis. See p 2007 In the present issue of Circulation , Sousa et al1 provide a first glimpse at the 1-year data after the implantation of sirolimus-eluting stents. The report describes a very small, noncontrolled registry, yet the results are striking. After 12 months of follow-up in 30 patients and 6 months of follow-up in an additional 15 patients, the authors demonstrate a uniquely stable result. Using the highly sensitive technique of intravascular ultrasound, only a very minor proliferative response to injury was observed (<3% luminal volume obstruction). By angiography, the percent diameter stenosis increased only slightly from a mean of near 10% at the procedure’s conclusion to ≈20% at 1 year. By the 12-month follow-up time point, not a single patient had sustained clinical or angiographic restenosis. These results are amplified by …

The PRESTO (Prevention of Restenosis with Tranilast and its Outcomes) protocol: A double-blind, placebo-controlled trial

The PRESTO (Prevention of Restenosis with Tranilast and its Outcomes) protocol: A double-blind, placebo-controlled trial

The PRESTO (Prevention of Restenosis with Tranilast and its Outcomes) protocol: A double-blind, placebo-controlled trial

Background Tranilast is a unique drug in clinical development for the prevention of restenosis after percutaneous transluminal coronary revascularization (PTCR). Tranilast interferes with proliferation and migration of vascular medial smooth muscle cells induced by platelet-derived growth factor and transforming growth factor β1. Collagen synthesis in vascular medial smooth muscle cells is inhibited by tranilast, which also inhibits the release or production of cyclooxygenase-2 and restores cytokine-induced nitric oxide production. These mechanisms may contribute to the reduction of angiographic restenosis after coronary intervention previously reported in clinical studies. Methods The primary objective of this multicenter study of 11,500 patients is to compare the composite clinical event rate of death, myocardial infarction, or the need for ischemia-driven target vessel revascularization of tranilast (300 and 450 mg twice daily) for 1 or 3 months with that of placebo in patients undergoing PTCR with or without stenting for single or multiple vessels over a 9-month period. The lesions can be de novo or restenotic. All revascularization procedures and the use of glycoprotein IIb/IIIa agents are permitted. The inclusion criteria are meant to allow an “all comer” approach for generalization of results to the broadest possible PTCR population. A subset population (n = 2000) will undergo 9-month follow-up angiography, 1000 of which will also undergo intravascular ultrasound (n = 1000). This study is the first tranilast trial to be conducted in a Western population to confirm the improved angiographic findings reported in Japanese patients and to determine if the clinical sequelae of restenosis are also reduced. Conclusion This multicenter study is the largest restenosis trial planned to date. It will test whether tranilast, a drug with multiple actions aimed at affecting proliferation and migration of vascular smooth muscle cells, can reduce clinical, angiographic, and intravascular ultrasound assessments of restenosis. (Am Heart J 2000;139:23-31.)