David Cloutier

Three-year clinical and angiographic follow-up after intracoronary radiation : results of a randomized clinical trial.

BACKGROUND Although several early trials indicate treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The objective of this report is to document angiographic and clinical outcome 3 years after treatment of restenotic stented coronary arteries with catheter-based (192)Ir. METHODS AND RESULTS A double-blind, randomized trial compared (192)Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Over a 9-month period, 55 patients were enrolled; 26 were randomized to (192)Ir and 29 to placebo. At 3-year follow-up, target-lesion revascularization was significantly lower in the (192)Ir group (15. 4% versus 48.3%; P<0.01). The dichotomous restenosis rate at 3-year follow-up was also significantly lower in (192)Ir patients (33% versus 64%; P<0.05). In a subgroup of patients with 3-year angiographic follow-up not subjected to target-lesion revascularization by the 6-month angiogram, the mean minimal luminal diameter between 6 months and 3 years decreased from 2.49+/-0.81 to 2.12+/-0.73 mm in (192)Ir patients but was unchanged in placebo patients. CONCLUSIONS The early clinical benefits observed after treatment of coronary restenosis with (192)Ir appear durable at late follow-up. Angiographic restenosis continues to be significantly reduced in (192)Ir-treated patients, but a small amount of late loss was observed between the 6-month and 3-year follow-up time points. No events occurred in the (192)Ir group to suggest major untoward effects of vascular radiotherapy. At 3-year follow-up, vascular radiotherapy continues to be a promising new treatment for restenosis.

Five-Year Clinical Follow-Up After Intracoronary Radiation Results of a Randomized Clinical Trial

Background—Several clinical trials indicate that intracoronary radiation is safe and effective for treatment of restenotic coronary arteries. We previously reported 6-month and 3-year clinical and angiographic follow-up demonstrating significant decreases in target lesion revascularization (TLR) and angiographic restenosis after &ggr; radiation of restenotic lesions. The objective of this study was to document the clinical outcome 5 years after treatment of restenotic coronary arteries with catheter-based iridium-192 (192Ir). Methods and Results—A double-blind, randomized trail compared 192Ir to placebo sources in patients with restenosis after coronary angioplasty. Over a 9-month period, 55 patients were enrolled; 26 were randomized to 192Ir and 29 to placebo. At 5-year follow-up, TLR was significantly lower in the 192Ir group (23.1% versus 48.3%;P =0.05). There were 2 TLRs between years 3 and 5 in patients in the 192Ir group and none in patients in the placebo group. The 5-year event-free survival rate (freedom from death, myocardial infarction, or TLR) was greater in 192Ir-treated patients (61.5% versus 34.5%;P =0.02). Conclusions—Despite apparent mitigation of efficacy over time, there remains a significant reduction in TLR at 5 years and an improvement in event-free survival in patients treated with intracoronary 192Ir. The early clinical benefits after intracoronary &ggr; radiation with 192Ir seem durable at 5-year clinical follow-up.

Two-Year Follow-Up After Catheter-Based Radiotherapy to Inhibit Coronary Restenosis

BACKGROUND Although early trials indicate the treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The possibility of late untoward consequences, such as aneurysm formation, perforation, and accelerated vascular disease, is of significant concern. Furthermore, it is not known whether the beneficial effects of radiation therapy will be durable or whether radiation will only delay restenosis. METHODS AND RESULTS A double-blind, randomized trial was undertaken to compare 192Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Patients were randomly assigned to receive a 0.76-mm (0. 03-in) ribbon containing sealed sources of either 192Ir or placebo. All patients underwent repeat coronary angiography at 6 months. All living patients were contacted 24 months after their index study procedure. Patients were assessed with respect to the need for target-lesion revascularization or nontarget-lesion revascularization, occurrence of myocardial infarction, or death. Over a 9-month period, 55 patients were enrolled; 26 were randomized to 192Ir and 29 to placebo. Follow-up was obtained in 100% of living patients at a minimum of 24 months. Target-lesion revascularization was significantly lower in the 192Ir group (15.4% versus 44.8%; P<0. 01). Nontarget-lesion revascularization was similar in 192Ir and placebo patients (19.2% versus 20.7%; P=NS). There were 2 deaths in each group. The composite end point of death, myocardial infarction, or target-lesion revascularization was significantly lower in 192Ir-treated versus placebo-treated patients (23.1% versus 51.7%; P=0.03). No patient in the 192Ir group sustained a target-lesion revascularization later than 10 months. CONCLUSIONS At 2-year clinical follow-up, treatment with 192Ir demonstrates significant clinical benefit. Although further follow-up (including late angiography) will be necessary, no clinical events have occurred to date in the 192Ir group to suggest major untoward effects of vascular radiotherapy. At the intermediate follow-up time point, vascular radiotherapy continues to be a promising new treatment for restenosis.

Effect of combined anticoagulation and low-dose aspirin treatment on upper gastrointestinal bleeding.

Multiple studies link the use of nonsteroidalantiinflammatory drugs (NSAIDs) with severe uppergastrointestinal bleeding (UGIB); the incidence of suchbleeding is 2-4%. One common regimen to assure patency after intracoronary stent placement requires ananticoagulant (warfarin) combined with aspirin as anantiplatelet agent. However, a 13-fold increase in therisk of UGIB occurs with long-term use of oral anticoagulants and NSAIDs. We retrospectivelyassessed the rate of UGIB in 138 patients who hadreceived coronary stents (group I, receiving heparinfollowed by warfarin in combination with aspirin) and 109 angioplasty patients without stents (groupII, receiving aspirin alone) between 1990 and 1994. UGIBwas identified by hematemesis or melena, which led togastrointestinal consultation. Patients were analyzed for multiple risk factors. UGIBoccurred in 28 of 138 group I patients (20%; 95% CI13.3-26.7%) and 0 of 109 group II patients (P ≤0.0001). Esophagogastroduodenoscopy (EGD) findings onthe 28 patients with UGIB included 13 patients with esophagitisor gastritis, 7 patients with gastric or duodenalulcers, and 8 patients with no identifiable source ofbleeding. UGIB occurred within a mean of 2.5 days of initiation of combination therapy. Ofpatients with UGIB, 10 required blood transfusion (meannumber of units 5.3). Previous history of peptic ulcerdisease, smoking, and use of antiulcer medication did not significantly differ between the twogroups. The concurrent use of anticoagulant and aspirinin patients with coronary stents creates a significantpotential for UGIB and should be used only with extreme caution.

A subgroup analysis of the scripps coronary radiation to inhibit proliferation poststenting trial

INTRODUCTION In the Scripps Coronary Radiation to Inhibit Proliferation Poststenting (SCRIPPS) Trial, 192Ir significantly reduced angiographic, ultrasonographic, and clinical endpoints of restenosis. The objective of this analysis was to quantitate the impact of patient, lesion and technical characteristics on late angiographic outcome. METHODS Patients with restenotic, stented coronary lesions were randomized to receive either 192Ir or placebo sources. Late luminal loss and loss index were calculated for several patient subgroups, including patients with diabetes, in-stent restenosis, multiple previous percutaneous transluminal coronary angioplasty (PTCA) procedures, longer lesion lengths, saphenous vein grafts, small vessel diameters, and minimum dose exposures < 8.00 Gy. Two-factor analysis of variance was used to test for an interaction between patient characteristics and treatment effect. RESULTS In the treated group, late loss was particularly low in patients with diabetes (0.19 mm), in-stent restenosis (0.17 mm), reference vessel diameters < 3.0 mm (0.07 mm), and patients who received a minimum radiation dose to the entire adventitial border of at least 8.00 Gy. The loss index in each of these subgroups was similarly low at -0.02, 0.03, -0.02, and 0.03, respectively. By 2-factor analysis of variance, a significant interaction between subgroup characteristic and treatment effect (late loss) was found in patients with in-stent restenosis (p = 0.035), and patients receiving a minimum dose of 8.00 Gy to the adventitial border (p = 0.009). CONCLUSION In this pilot study, patient characteristics associated with a more aggressive proliferative response to injury appeared to confer an enhanced response to radiotherapy. Furthermore, a dose threshold response to 192Ir was found with an enhanced response occurring when the entire circumference of the adventitial border was exposed to at least 8.00 Gy.

Portal Decompression by Transjugular Intrahepatic Portosystemic Shunt and Changes in Serum-Ascites Albumin Gradient

The serum ascites albumin gradient (SAAG) is widely used to help determine the cause of ascites formation. A serum ascites albumin gradient of > or = 1.1 g/dL reliably distinguishes portal hypertension-related ascites from other causes. To date, there are no published data on the impact of portal decompression on this gradient. The recent development of transjugular intrahepatic portosystemic shunt (TIPS) allows for nonsurgical decompression of portal hypertension by radiologically creating a portosystemic shunt. This study examines the short-term impact of portal decompression on the serum ascites albumin gradient (SAAG) in patients with portal hypertension-related ascites undergoing transjugular intrahepatic portosystemic shunt. Portal pressure measurements were obtained before and after TIPS placement. Serum ascites albumin gradient was determined before and at 6 and 24 hours post-TIPS placement. Fifteen patients were enrolled in the study. The mean portosystemic gradient (PSG) before TIPS was 21.0 +/- 9.2 mmHg, whereas the post-TIPS mean PSG was reduced to 11.0 +/- 6.3 mmHg, consistent with portal decompression (p = 0.005). The mean pre-TIPS serum ascites albumin gradient was 1.9 +/- 0.5 g/dL and was reduced to 1.7 +/- 0.5 g/dL at 6 hours (p = 0.003) and 1.4 +/- 0.4 g/dL at 24 hours (p = 0.002) after TIPS placement. These findings further solidify the association between the SAAG and portal hypertension.