Beta-Radiation Investigation With Direct Stenting and Galileo in Europe - BRIDGE (beta-radiation)

Description:

The goal of the trial was to evaluate the efficacy of vascular brachytherapy (VBT) combined with direct stenting compared with direct stenting alone for the primary prevention of restenosis in de novo lesions treated with optimal adjunctive therapy.

Hypothesis:

Treatment with direct stenting plus VBT will be associated with a lower rate of restenosis compared with direct stenting alone in de novo lesions.

Study Design

Patients Enrolled: 112
Mean Follow Up: One year
Mean Patient Age: Mean 61 years
Female: 21

Patient Populations:

De novo lesions in one or two native vessels with a reference diameter of 2.5-4.0 mm and a lesion length of 15 mm suitable for direct stenting; stable (Canadian Cardiovascular Society class I, II, III, or IV) or unstable angina pectoris (Braunwald class I to III, B to C); or documented silent ischemia

Exclusions:

Any MI within three days before inclusion and/or lack of normalization of the creatine phosphokinase; previous Q-wave MI in the territory supplied by the vessel to be treated and a large akinetic area in the same territory; stroke/gastrointestinal bleeding within six months; ejection fraction <30%; severe="" hepatic="" disease;="" previous="" mediastinal="" irradiation;="" known="" intolerance="" or="" contraindication="" to="" aspirin,="" clopidogrel,="" or="" glycoprotein="" iib/iiia="" inhibitors;="" total="" occlusion="" (timi="" flow="" grade="" 0);="" stenting="" of="" each="" arm="" of="" a="" bifurcation;="" and="" intended="" angioplasty="" of="" the="" ostium="" of="" the="" left="" anterior="" descending="" and="" left="" circumflex="" coronary="" artery="" to="" avoid="" impeding="" the="" flow="" in="" the="" main="" stem="" with="" the="" centering="" catheter="" severe="" hepatic="" disease;="" previous="" mediastinal="" irradiation;="" known="" intolerance="" or="" contraindication="" to="" aspirin,="" clopidogrel,="" or="" glycoprotein="" iib/iiia="" inhibitors;="" total="" occlusion="" (timi="" flow="" grade="" 0);="" stenting="" of="" each="" arm="" of="" a="" bifurcation;="" and="" intended="" angioplasty="" of="" the="" ostium="" of="" the="" left="" anterior="" descending="" and="" left="" circumflex="" coronary="" artery="" to="" avoid="" impeding="" the="" flow="" in="" the="" main="" stem="" with="" the="" centering="">

Primary Endpoints:

Angiographic intrastent late loss

Secondary Endpoints:

&bull; Event-free survival at one year, defined as the absence of major adverse cardiac and cerebrovascular events (MACCE). MACCE included cardiac death, cerebrovascular events, MI, and target vessel revascularization.
&bull; Binary angiographic restenosis at six months.
&bull; Neointimal hyperplasia at six months, as assessed by IVUS.

Drug/Procedures Used:

Patients with de novo lesions were randomized to direct stenting alone (n=58) or direct stenting followed by VBT with P-32 (20 Gy at 1 mm in the coronary wall; n=54). Angiographic and intravascular ultrasound (IVUS) follow-up was performed at six months.

Concomitant Medications:

All patients were treated with clopidogrel 75 mg and aspirin 80 mg daily for up to 11 months.

Principal Findings:

Glycoprotein IIb/IIIa inhibitors were used in 95% of patients. The target vessel was the left anterior descending artery in approximately half of the cases. Most patients were in Canadian Cardiovascular Society class II (39% for the irradiation group and 33% for no irradiation group) or class III (18.5% and 25.9%, respectively). There were 57 lesions in the irradiation group and 59 in the no irradiation group.

The primary endpoint of in-stent late loss on angiographic follow-up was lower in the irradiation group compared with control (0.43 vs. 0.84 mm, p<0.001). percent="" diameter="" stenosis="" trended="" lower="" in="" the="" irradiation="" group="" (23%="" vs.="" 30%,="" p="0.07)," but="" there="" was="" no="" significant="" difference="" in="" binary="" restenosis="" (12.7%="" vs.="" 13.2%,="" p="1.00)." late="" total="" occlusions="" (="">30 days) occurred in six patients, all randomized to the irradiation group (10.9% per lesion, p=0.03), but one patient did not receive the randomized irradiation treatment. Neointimal volume on IVUS at follow-up was lower in the irradiation group (10 vs. 36 mm3, p<0.001), as="" was="" obstruction="" volume="" (5%="" vs.="" 21%,="">

There were no deaths during the follow-up period. Major adverse cardiac events occurred in 25.9% of patients in the irradiation group and 17.2% in the control group (p=0.36). Revascularization was performed in 20.4% and 12.1%, respectively (p=0.31).

Interpretation:

Among patients with de novo coronary lesions treated with optimal adjunctive therapy, direct stenting with VBT was associated with a reduction in the primary endpoint of in-stent late loss at six-month angiographic follow-up. Additionally, improvements in IVUS parameters were observed at six months. Despite the angiographic and IVUS benefits, there was no difference in clinical events, and the VBT group actually had a higher rate of late total occlusion, even though all patients received antithrombotic therapy.

Prior studies have shown a benefit with use of brachytherapy for treatment of restenosis, but the benefit of brachytherapy for prevention of restenosis in de novo stented lesions has not been as consistent. Given the success of drug-eluting stents in preventing restenosis and the complexity of brachytherapy, it is unlikely brachytherapy will be used for widespread primary prevention of restenosis.

References:

Serruys PW, Wijns W, Sianos G, et al. Direct stenting versus direct stenting followed by centered beta-radiation with intravascular ultrasound-guided dosimetry and long-term anti-platelet treatment: Results of a randomized trial: Beta-radiation investigation with direct stenting and galileo in Europe (BRIDGE). J Am Coll Cardiol 2004;44:528-37.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Prevention, Interventions and Coronary Artery Disease

Keywords: Coronary Artery Disease, Beta Particles, Drug-Eluting Stents, Constriction, Pathologic, Fibrinolytic Agents, Brachytherapy, Primary Prevention


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