The SCRIPPS trial--catheter-based radiotherapy to inhibit coronary restenosis

The SCRIPPS trial is a randomized, double-blind, placebo-controlled trial evaluating the impact of gamma radiation to inhibit in-stent restenosis. Fifty-five patients were enrolled; twenty-six were assigned to receive catheter-based radiation with Ir-192 and 29 were treated with placebo. Angiographic restenosis in the Ir-192-treated patients was significantly reduced at six months (17% vs. 54%; p = 0.01), with the results sustained at 3-year follow-up (33.3% vs. 63. 6%; p<0.05). Likewise, the composite clinical endpoint of death, myocardial infarction or target lesion revascularization was also commensurately lower in the treated group as compared to the placebo group (23.1% vs. 55.2%; p = 0.01). Late angiography revealed no perforation, aneurysm or pseudoaneurysm or special safety issues unique to radiotherapy.     

Thoracic radiotherapy in patients with lymphoma and restenosis after coronary stent placement.

OBJECTIVES: The aim of this study was to assess the incidence of restenosis after coronary stenting in patients with lymphoma treated with thoracic radiation. BACKGROUND: Patients with Hodgkin lymphoma treated with thoracic radiation have an increased incidence of coronary artery disease (CAD). The incidence of restenosis after percutaneous coronary interventions is completely unknown. METHODS: This study included 12,626 consecutive patients with CAD treated with coronary stenting during a 10-year period. Within this cohort, three subgroups of patients were assessed: patients with lymphoma and previous thoracic radiation (15 patients), patients with lymphoma without thoracic radiation (7 patients) and patients without lymphoma or previous thoracic radiation (control group; 12,604 patients). Coronary stenting was performed after a median [25th; 75th percentiles] of 8 years [4; 17] after thoracic radiation. The primary end point of the study was restenosis at 6-month coronary angiography. RESULTS: Six-month coronary angiography was performed in 14 patients (93%) in the group with lymphoma and radiation, 6 patients (86%) in the group with lymphoma without radiation and 10,032 patients (80%) in the control group (P = 0.38). Angiographic restenosis was found in 12 patients (85.7%) in the group with lymphoma and radiation, 1 patient (16.7%) in the group with lymphoma without radiation and 2,555 patients (25.5%) in the control group (P < 0.001). Multiple logistic regression identified thoracic radiation as an independent predictor of coronary restenosis (odds ratio 21.7, 95% confidence interval, 4.7-100.9, P < 0.001). CONCLUSIONS: Patients with lymphoma treated with thoracic radiation have an increased risk of restenosis after coronary artery stenting.     

Two-year follow-up of percutaneous coronary intervention using EucaTax or Cypher

BackgroundThe EucaTax stent (EUPES) is a coronary stent with biodegradable polymer and camouflage coating that has been developed to promote the complete elution of drugs and decrease the risk of late complications. The aim of this study was to evaluate the efficacy and safety of the double-coated EUPES in patients with stable angina versus sirolimus-eluting stent CYPHER (SES) with permanent polymer coating.Methods and MaterialsThe study included consecutive patient with at least 70% de novo coronary lesions in one or two native coronary arteries and who had undergone the coronary stenting using either EUPES or SES. We evaluated the 2-year major adverse cardiac events (MACE) rates, including total death (cardiac, non-cardiac), myocardial infarction (MI), target lesion revascularisation (TLR) and stent thrombosis.ResultsBetween 2006 and 2009 this observational, prospective, single centre study included 602 patients (282 with EUPES and 320 with SES). At 2 years, the rates of TLR (16.3% versus 6.25%; p = 0.0001) and MACE (18.4% versus 7.8%; p = 0.001) were significantly higher in the EUPES than in the SES group. The rate of TLR was significantly higher in the EUPES group compared with SES group in stenting of artery with a diameter less than 3 mm, using stent length more than 18 mm, as well as when the residual stenosis was more than 12%.ConclusionsWe found that EUPES was inferior to SES during the 2-year follow-up with respect to rates of MACE and TLR that were significantly higher in the EUPES than in the SES group.     

New catheter-based technology for the treatment of restenosis

Catheter-based vascular interventions have been in development worldwide for several decades, leading to remarkable progress in device technology. Mechanical interventional devices, such as angioplasty balloons, atherectomy devices, and stents, were invented and have contributed greatly to the treatment of atherosclerotic vascular stenosis. However, mechanical approaches do not effectively prevent subsequent intimal growth. Recently, several biological approaches, including radiation therapy and drug-eluting stents, have shown striking inhibition of intimal growth. These significant results are likely to change the treatment strategy in the field of interventional cardiology. Furthermore, additional catheter-based technologies for vascular interventions are presently being evaluated. These latest technologies designed to prevent intimal proliferation include intravascular sonotherapy, cryotherapy, photoangioplasty, and soft X ray. To date, intravascular sonotherapy has proven its efficacy in animal studies and safety in human studies. Cryotherapy, the application of cold thermal energy during angioplasty, enhances the acute effects of conventional dilation while decreasing the likelihood of restenosis. Photoangioplasty has a unique property based on its selective mechanism of action to treat atheromatous plaque. Soft X ray systems provide convenient device handling and well-controlled radiation dose. Some of these technologies may play an important role in vascular interventions in the near future.     

Medical approaches to prevention of restenosis after coronary angioplasty

Although initial success rates for coronary angioplasty have improved, the rate of restenosis within 6 months of the procedure has persisted at 30 to 40%. The relation of restenosis to initial success, recurrence of symptoms and risk factors suggests that high grade or total lesions, long lesions, lesions in the proximal left anterior descending artery or in saphenous grafts, and the absence of intimal dissection after angioplasty are associated with an increased risk of restenosis. Unstable angina, male sex and diabetes are clinical factors associated with a greater risk of restenosis. Pathologic specimens suggest that plaque splitting and disruption are found acutely after angioplasty, but that restenosis occurs as an excessive reparative, proliferative response of smooth muscle cells leading to recurrent luminal narrowing. A prospective analysis of therapeutic interventions to prevent restenosis, such as administering antiplatelet and lipid-lowering agents, intensive diabetic therapy and administration of calcium antagonists, is proposed. Problems with timing of studies, design and sample size are considered. Current recommendations for anti-restenosis therapy include antiplatelet therapy before and after angioplasty, administration of heparin in some patients and intensive risk factor intervention for the 6 months after the procedure.     

Prevention of restenosis after coronary angioplasty

PURPOSE OF REVIEW: Despite numerous advances in coronary interventional techniques, the frequent occurrence of restenosis continues to plague interventional cardiology. With the widespread use of drug-eluting stents, there is a need to reexamine critically the roles of the various interventional techniques currently available. RECENT FINDINGS: Drug-eluting stents have dramatically reduced the rates of restenosis and target vessel revascularization in a wide spectrum of patients with varying lesion morphologies. However, when restenosis does occur, it still tends to be dependent on the same factors that predict restenosis with bare metal stenting. The routine use of drug-eluting stents entails high initial costs to the health care system. Debulking as a means to improve outcomes after angioplasty has not lived up to expectations. Gene therapy is rapidly evolving into a viable means to reduce neointimal proliferation after angioplasty. SUMMARY: Careful patient selection and attention to the procedure of stent deployment optimize the results of angioplasty with drug-eluting stents. Because of cost considerations, drug-eluting stents should be used in patients who are expected to have the greatest absolute benefit. In this context, when judiciously used, conventional balloon angioplasty and bare metal stenting still have a definite role in the management of patients with obstructive coronary artery disease.     

Consequences of restenosis after coronary angioplasty

The consequences of restenosis after angioplasty were evaluated in 466 patients who had coronary angiography 3 to 12 months after successful coronary angioplasty and were followed long term. The 236 subjects with restenosis resembled the 230 without restenosis with respect to age, sex, presence of multivessel disease, mean ejection fraction, prior myocardial infarction, prior coronary artery bypass grafting, and completeness of revascularization. The 5-year relative risk of revascularization for patients with restenosis markedly exceeded that for patients without restenosis. The relative risk of repeat angioplasty in the former group was 4.26 times that in the latter group (95% confidence interval, 2.80 to 6.51), and the risk of coronary artery bypass grafting in patients with restenosis was 3.68 (95% confidence interval, 2.16 to 6.28). There was no difference between the 2 groups in the relative risk of myocardial infarction or death. When the completeness of revascularization was considered, patients with incomplete revascularization and restenosis had the worst outcomes, with 50% needing coronary artery bypass grafting within 5 years. Early restenosis markedly increases the probability of revascularization, but it has little effect on infarction or mortality. Even when early restenosis is absent, further revascularization procedures are still frequent. A solution to the problem of restenosis might reduce by half the need for revascularization during the subsequent 5 years.     

Clinical and angiographic follow-up after balloon angioplasty with provisional stenting for coronary in-stent restenosis.

The objective of this study was to assess the angiographic and clinical outcome of patients with coronary in-stent restenosis treated with balloon angioplasty with provisional stenting. The study included 375 consecutive patients with in-stent restenosis managed with balloon angioplasty alone or combined with stenting. Clinical events were recorded during a 1-year follow-up period and quantitative analysis was performed on 6-month angiographic data. Of the 373 patients (451 lesions) with a successful procedure, 273 were treated with angioplasty alone and 100 with additional stenting. Target lesion revascularization was required in 23.7% of the patients: 20.7% in patients with angioplasty and 31.0% in patients with stenting. Angiographic restenosis rate was 38.9%: 35.8% in the angioplasty group and 47.7% in the stent group. Stenting in small vessels was associated with a much higher restenosis rate than in larger vessels (65.6% vs. 37.5%, respectively; P = 0.01). Thus, repeat balloon angioplasty with provisional stenting for in-stent restenosis is a safe treatment strategy associated with a relatively favorable long-term outcome. However, the long-term results might be improved if additional stenting is avoided especially in small vessels. Cathet. Cardiovasc. Intervent. 48:151-156, 1999.     

Usefulness of predictors of angiographic restenosis to predict clinical restenosis after coronary stent placement

INTRODUCTION: After coronary stenting, several predictors of angiographic in-stent restenosis have been identified in different studies, however, little is known about predictors of clinical restenosis, a more functional aspect of coronary restenosis. AIM: To assess whether risk factors for angiographic restenosis previously described, are able to predict clinical restenosis and at what rate in current practice. PATIENTS AND METHODS: 216 consecutive patients (271 stents in 256 lesions) with procedural success were followed-up for 17.6 +/-10 months during periodic visits. Clinical restenosis was defined as the presence of symptoms or signs of myocardial ischemia, associated with >= 50% diameter stenosis on the angiogram. RESULTS: Clinical restenosis occurred in 33 lesions (13%), which were revascularized with 34 stents associated with unstable angina in 29, acute myocardial infarction in three and death in one case. Multivariate analysis identified as independent predictors of clinical restenosis, a vessel diameter less than 3 mm (p < 0.001, OR 4.5), a restenotic lesion (p = 0.01, OR 2.9) and the presence of residual stenosis by visual estimate (> 0%) after implantation (p = 0. 02, OR 2.5). These three risk factors explained most clinical restenosis (73%), with rates of 22% when at least one was present and 4% in absence of all these. The presence of diabetes mellitus, the location in the anterior descending coronary artery or at coronary ostium, and the number or total length of stents per lesion did not achieve an independent, significant association as predictors of clinical restenosis. CONCLUSIONS: Most clinical restenosis after coronary stenting can be predicted by the restenotic character of the revascularized lesion, the diameter of the vessel being less than 3 mm and the presence of residual stenosis by visual estimate at the end of procedure.