Borrowing from the field of radiation oncology, cardiovascular interventionalists have found that therapeutic radiation offers an effective means to prevent in-stent restenosis of intracoronary stents and restenosis of peripheral vessels treated by angioplasty.
In clinical studies, intracoronary radiation has consistently reduced the incidence of in-stent restenosis, by as much as 70% in some instances. The success has prompted speculation that intracoronary radiation eventually might become standard adjunctive therapy for coronary stent implantation. Other investigators offer a more cautious assessment.
"First things first," said Dr. Ron Waksman, an interventional cardiologist at Washington Hospital Center in Washington, DC. "We expect that intracoronary radiation will be approved for treatment of in-stent restenosis by the end of the year. It has proven effective for that indication. Once the therapy receives that approval, then we can begin thinking about use of the therapy in patients who are at risk for in-stent restenosis."
Results are more preliminary but appear equally promising for vascular brachytherapy of peripheral arteries. Initial results of a large ongoing clinical trial show a 90% patency rate at 12 months in claudication patients who received brachytherapy plus percutaneous transluminal angioplasty (PTA).
Vascular brachytherapy requires a multidisciplinary team to insert radiation-containing "ribbons" or "trains" into vessels at the site of stenosis. A typical procedure requires a vascular interventionalist to insert a delivery catheter and a therapeutic radiologist to place the radiation source.
Several reports at the American College of Cardiology meeting in March focused on the role of coronary and peripheral vascular brachytherapy. Dr. Paul Teirstein, an interventional cardiologist at the Scripps Clinic in La Jolla, CA, said intracoronary radiation has dramatically reduced recurrenceof in-stent restenosis after initial treatment.
"Some patients come back to the catheterization laboratory every two to three months with in-stent restenosis," Teirstein said. "We needed another solution, so we got the idea to use radiation in much the same way radiation oncologists use it to treat benign proliferative disorders, such as keloid formation or heterotopic ossification."
The risk of in-stent restenosis can range as high as 80% to 90% in some patients, such as those with long atherosclerotic lesions, he said.
In a preliminary clinical study conducted by Teirstein and colleagues, the incidence of in-stent restenosis declined from 54% without intracoronary radiation to 17% with radiation, a difference of almost 70%. Need for repeat revascularization procedures was reduced 74%, from 45% to 12% (NEJM 1997;336:1697-1703, and Circulation 2000;101-350-351).
Waksman reported that intracoronary radiation reduced the rate of in-stent restenosis from 71% to 32% in patients with long lesions (up to 80 mm in length). The incidence of in-lesion restenosis was reduced from 78% to 46% following placement of source trains seeded with iridium-192. At follow-up angiography, patients who received intracoronary radiation had significantly larger average minimum lumen diameter (1.4 mm versus 1.01 mm, p = 0.008).
In another study reported at the ACC, Harvard Medical School cardiologist Jeffrey Popma and colleagues found substantially better outcomes in 476 patients randomized to intracoronary radiation with strontium-90 versus placebo for in-stent restenosis. Radiation treatment reduced the incidence of target vessel revascularization by 33%, target lesion revascularization by 42%, and major adverse cardiac events by 31%.
Also at the ACC, Waksman reviewed the status of peripheral vascular brachytherapy. Early studies by German and Austrian investigators showed patency rates as high as 82% at five years. Investigators at the University of Vienna have conducted a series of clinical studies of peripheral brachytherapy. In the largest of the trials, radiation therapy was associated with a 50% reduction in the incidence of restenosis, Waksman said. However, the trials have involved relatively few patients.
Investigators in an ongoing U.S. trial will evaluate peripheral brachytherapy in 300 patients with claudication. The patients are being randomized to PTA alone or PTA plus radiation therapy. All the patients have superficial femoral artery stenoses at least 5 cm in length. Waksman revealed findings from the first 41 patients enrolled in the trial.
Among 40 evaluable patients, the radiation was successfully delivered in 35. At six-month angiographic follow-up, 27 of 30 evaluable patients had patent vessels. Clinical follow-up at 12 months in the same 30 patients indicated that 27 still had patent arteries. Reintervention in the same vessel has been required in 13% of cases. Performance on walking tests has improved notably between enrollment and 12 months after treatment. No in-hospital adverse events occurred.
"These are very impressive results," Waksman said. "The initial results show that radiation therapy produces angiographic and clinical benefits. I think we can anticipate that brachytherapy for PTA will probably imitate what we have seen in coronary arteries, but we need complete results from the randomized trial to get a definitive answer about the safety and efficacy of the therapy."
Intravascular radiation therapy is not without its own complications, Waksman noted. The most prominent problems are late thrombosis and occurrence of the so-called edge effect. When a radiation source train inadequately covers the treatment area, restenosis may occur at the edges of the treatment field.
