Early Clinical Results for Drug-Eluting Balloons

The March issue of Vascular Disease Management features an interview on drug-eluting balloon (DEB) technologies with Dr. Scheinert. Drug-eluting balloon therapy is a transformative technology that will result in improved patency in patients undergoing interventional therapy of superficial femoral and popliteal arterial obstructions. Whereas most interventions on these arteries are performed for the treatment of disabling claudication, patency of these vessels may also be important in cases of critical limb ischemia, which is often the product of multilevel disease. Interventionists in the United States are trying to determine the most appropriate use of these devices, particularly now when they create incremental cost to catheterization labs with no offsetting revenue.

In Europe, several DEBs are approved for clinical use. These primarily utilize paclitaxel as the therapeutic agent with different excipients to aid in drug delivery. Two DEBs (Bard Lutonix and Medtronic In.Pact DES) have been approved by the FDA for clinical use in the United States. The drug dose varies from device to device but the amount of drug delivered by any of the DEBs is dramatically less than the dosing administered in chemotherapy treatments. Third-party coverage is available in some of European countries where DEBs are available and not in others. Utilization of these devices is far greater in those countries with third-party insurance coverage. Improved long-term patency with these devices has the potential to decrease overall health care costs and lessen the risk of repeated interventional procedures. 

There are no trials with head-to-head comparison of different DEBs. Multiple trials, however, have shown that DEBs in general are superior to standard balloon angioplasty. It is highly probable that there is an overall class effect but that there may be substantial differences between various devices. These devices have not been studied extensively in densely calcified lesions or in cases where there has been a poor final angioplasty result. Trials combining DEBs with atherectomy are being conducted to discern if there is an additive effect. DEB trials in the therapy of in-stent restenosis are also being conducted. Results of these trials may provide valuable insight as to DEBs’ role in treating these difficult clinical problems.

There are many unanswered questions on DEB technology. Initial research suggests that different excipients have substantial clinical drug delivery impact. Which excipient will prove most effective? Does one dose of paclitaxel fit all pathologies? Can we effectively deliver drug in severely calcified arteries? Are results different with subintimal vs true luminal angioplasty with DEBs? Is paclitaxel the appropriate drug in all cases? Despite initial encouraging single-center reports in infrapopliteal disease, the In.Pact Deep trial showed discouraging results and was prematurely discontinued secondary to poor inhibition of intimal ingrowth and a signal of a potential trend toward more amputations. Was this statistical aberration or a true signal? Does the drug impair wound healing? Are there more effective ways of delivering drugs that inhibit restenosis than diffusion from a balloon via an excipient? Drug-eluting balloons are an exciting new therapeutic option in the treatment of peripheral vascular disease that are a source of great hope in the thus far elusive goal of preventing restenosis in peripheral vascular interventions. 

Editor's note: On February 19, 2015, Medtronic announced that the US Centers for Medicare and Medicaid Services approved payment of the In.Pact Admiral drug-eluting balloon. See Dr. Walker's related video message, "Clinical Results and New Frontiers for Drug-Eluting Balloons."