Coronary Brachytherapy: Still Relevant in the Era of Drug-Eluting Stents

After FDA approved drug-eluting stents (DES) about 10 years ago, clinical studies demonstrated that in-stent restenosis (ISR) due to the growth of smooth muscle cells during healing was not as widespread of an issue as it had been with bare metal stents. Due to the improved efficacy of DES, Cleveland Clinic took a hiatus from offering vascular brachytherapy (VBT) to treat ISR.

However, over time, the Heart & Vascular Institute’s Interventional Cardiology team has determined that adjunctive intracoronary radiation therapy is a treatment modality that still has value even in the era of DES. VBT is now an option again in carefully selected patients.

“Since drug-eluting stents work both mechanically and pharmacologically, the risk of restenosis vs bare metal stents has decreased from about 10 to 30 percent, to 5 to 15 percent,” says Stephen Ellis, MD, Section Head of Invasive & Interventional Cardiology in the Miller Family Heart & Vascular Institute.

“However, in-stent restenosis is clearly still an issue in some patients,” he says. “Because we are a referral center, we were seeing more and more patients with tough blockages that we knew could benefit from brachytherapy.”

Certain risk factors — such as diabetes, longer stents, small blood vessels and multiple stents — may increase the likelihood of ISR. “We have learned that restenosis is a very complex process,” Dr. Ellis says.

Cleveland Clinic is one of only a few centers in the country — and the only one in Northeast Ohio — that offers VBT.

Clinical protocols

At Cleveland Clinic, VBT is performed by an interventional cardiologist in collaboration with a radiation oncologist and radiation physicist. Following balloon angioplasty, the therapy uses highly specialized protocols to deliver a small amount of targeted Beta radiation via radioactive ribbon to prevent repeat ISR. “This kills or stuns some of the cells that lead to restenosis,” Dr. Ellis says.

The radiation dose and dwell time, which are dependent on the size of the blood vessel determined by intravascular ultrasound (IVUS), are precisely calibrated by the radiation team.

VBT is an alternative to locally administered sirolimus or cilostazol. “While both of these drugs have been shown to reduce blockages, neither is a homerun,” Dr. Ellis says. “Our treatment choice is very individualized. Sirolimus has better data behind it, but it can be toxic and somewhat expensive. Cilostazol is generally better tolerated but has side effects, too. We usually use sirolimus if the patient can afford it because it’s more powerful.”

Patient selection matters

While VBT is an important tool in the interventional cardiologist’s tool box, it’s not for everyone, Dr. Ellis says. Careful patient selection is critical and it’s typically not a first-line treatment following a single occurrence of ISR. “VBT is an advanced therapy that may be considered in certain patients after ISR has occurred two or three times,” Dr. Ellis says.

In addition, certain patients — such as those who have received therapeutic radiation to treat breast cancer or cancers in the thoracic region — are not candidates.

“We do about 10,000 heart catheterizations a year, and we will treat about 10 to 20 of those patients with brachytherapy,” he says.

Determining who’s a candidate

Patients with ISR are carefully assessed to determine if they might benefit from VBT or another treatment, such as cutting balloon angioplasty and another stent, or even coronary artery bypass graft (CABG) surgery in extreme cases.

“The approach to addressing restenosis is highly individualized, and includes a number of options based on the principle cause of the restenosis, the size of the blockage, whether the patient has restenosis in multiple spots, and the number of stents the patient may already have in one area,” Dr. Ellis says. “The way the blockage comes back in part determines the likelihood that it will become a recalcitrant problem and to a certain extent guides therapy.”

Generally, the number of stents placed in one spot should not exceed three, he says. When it has, VBT plus preventive drugs can offer a valuable treatment option.

In order to determine if a patient is a candidate for VBT, IVUS or intracoronary optical coherence tomography is used to ensure that the restenosis is due to a proliferation of scar tissue during initial healing following stent placement, and not due to an inadequately inflated balloon during placement.

Durability: More studies needed

After VBT is performed, patients are placed on standard anti-clotting drug regimens such as therapeutic aspirin and/or clopidogrel.

In the short term, VBT decreases restenosis by about 50 percent. However, the therapy may have some limitations as far as durability. When VBT is performed in conjunction with bare metal stents, clinical studies have shown that the restenosis may return in the same spot within 5 years of treatment. More research is needed regarding durability when used to treat restenosis in DES, Dr. Ellis says.

For more information or to refer a patient, contact the Heart & Vascular Institute at 800.223.2273, ext. 46697.