Sirolimus-eluting balloon emerges as a safe and effective option for coronary in-stent restenosis

A new drug-eluting balloon can perform just as well as the standard treatment for patients with coronary in-stent restenosis (ISR) undergoing repeated percutaneous coronary intervention (PCI). These breakthrough findings of an international clinical trial led by a Mount Sinai researcher could transform the way this patient population is treated.

This is the first U.S.-regulated, and largest randomized, trial to compare a balloon coated with the drug sirolimus against the current standard of care for ISR, which includes both repeat stenting and balloon angioplasty. It could lead to a safer and simpler alternative for patients who need repeat PCI.

Significant results from the "SELUTION4ISR Trial" were presented during a Late Breaking Clinical Trial session at the Transcatheter Cardiovascular Therapeutics conference in San Francisco on October 26.

For the first time, we've shown that a sirolimus-eluting balloon can match the outcomes of standard care for in-stent restenosis while avoiding yet another metal layer. This opens the door to treating restenosis in a simpler, safer way. This study represents an important advance in how we manage restenosis. Patients with multiple stent layers have long faced limited options. A drug-eluting balloon that performs as well as a new stent could be a true paradigm shift."

Roxana Mehran, MD, co-Principal Investigator, Director of Interventional Cardiovascular Research and Clinical Trials at the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai

ISR occurs when a coronary artery becomes narrow again after a successful PCI procedure is performed to open that blocked artery. PCI is a non-surgical procedure in which interventional cardiologists use a catheter to place stents in the blocked coronary arteries to restore blood floor.

The standard treatment for initial and repeated PCI involves implanting a metallic drug-eluting stent, a permanent metallic implant that effectively opens the artery. Patients are also put on an antiplatelet therapy. ISR patients require additional stents, and repeated use of these metallic stents remains a persistent problem. For those who cannot tolerate another stent or prolonged antiplatelet therapy, interventional cardiologists use a balloon that is not drug-coated to expand the artery. Roughly 1 in 10 PCI procedures are performed in the United States to treat ISR every year, which translates into thousands of cases. Each time a new stent is added, more metal layers build up inside the artery, which can make future procedures harder and increase the risk of recurrent ischemic events including heart attack and stent restenosis.

Drug-coated balloons using the medication paclitaxel, which are approved by the Food and Drug Administration, are another treatment option to reopen the artery in patients with diabetes or high bleeding risk.

In this trial, researchers analyzed a new drug-eluting balloon called the Selution Sustained Limus Release Balloon. It uses sirolimus, also known as rapamycin, which is a potent immunosuppressive medication. This inhibits the growth and migration of smooth muscle cells and inflammatory cells that contribute to restenosis. 

Investigators enrolled 418 patients with coronary ISR who had either one or two previous stents in this multicenter, single-blind, randomized trial. Of the participants, 197 were treated with the sirolimus balloon, while 193 received standard care (80 percent of these received new drug-eluting stents and 20 percent had plain balloon angioplasty using balloons not coated with a drug). The primary outcome was target lesion failure at the one-year mark following the procedure.They tested to see if results from the sirolimus balloon were within an acceptable margin of standard care.

One-year results showed that target lesion failure was similar between the groups, with 16.2 percent in patients treated with the sirolimus balloon compared to 13.5 percent who received standard care, a difference that is not statistically significant. The proportion of patients who needed clinically indicated repeat procedures at the treated site was nearly identical in both groups, 12.7 percent for sirolimus balloons versus 12.4 percent for standard care. The new balloon performed similarly overall to standard treatments. However, repeat stenting for patients with only one previous stent layer performed somewhat better than the balloon. Additionally, among patients treated with balloon angioplasty alone, the sirolimus balloon outperformed plain balloons.

"Patients who develop in-stent restenosis may now have a metal-free treatment option that works about as well as another stent in many cases. This may be particularly valuable for those who already have multiple stent layers, where adding more metal may increase risk or complicate future procedures," adds Dr. Mehran. "For interventional cardiologists, this study provides evidence supporting sirolimus-eluting balloons as a viable alternative for patients with complex or multilayer ISR, where repeat stenting may not be ideal. It also reinforces the importance of tailoring therapy to the number of stent layers and lesion characteristics."

Researchers are conducting long-term follow-up through five years to evaluate durability of these results. Further studies will test the device in broader populations, including those with more than two stent layers or in smaller vessels. Also, comparative cost-effectiveness and quality-of-life analyses are warranted.

This trial was funded by M.A. Med Alliance SA (a Cordis Company).