March 19, 2015

3 Takes on 3 Emerging Strategies for Preventing Restenosis After Percutaneous Vascular Intervention

Drug-coated balloons, vascular brachytherapy, refining duration of dual antiplatelet therapy

Restinosis

Three decades after the advent of percutaneous intervention for treatment of various forms of atherosclerotic vascular disease, optimal methods of preventing the most common complications after treatment — restenosis and thrombosis — are still under active investigation.

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Although these complications have become less frequent with newer technology and pharmacotherapy, a number of recent developments promise further improvements. These include:

  • Approval of the first drug-coated angioplasty balloon catheters for treatment of peripheral artery disease (PAD)
  • The re-emergence of vascular brachytherapy as an option for preventing restenosis in carefully selected patients
  • Improved understanding of the appropriate duration of dual antiplatelet therapy in recipients of coronary stents

Consult QD caught up with three Cleveland Clinic interventional cardiologists for their perspectives on how these developments are shaping therapy.

Drug-coated balloons: Real-world lessons begin

In October 2014, the FDA approved a paclitaxel-coated angioplasty balloon catheter — the Lutonix® 035 DCB — for percutaneous transluminal angioplasty, after predilatation, for the treatment of de novo or restenotic stenoses in superficial femoropopliteal arteries as a result of PAD. The paclitaxel-coated balloon is approved for treating stenoses up to 150 mm long in these arteries.

The dose of paclitaxel used is 300 times lower than the dose used as chemotherapy, and only about 10 percent of that is delivered to the vessel wall, says Mehdi Shishehbor, DO, MPH, PhD, Director of Endovascular Services in the Department of Cardiovascular Medicine.

FDA approval was supported by results of the international LEVANT 2 pivotal trial, which included 476 patients — including some enrolled at Cleveland Clinic — with angiographically significant stenoses in the superficial femoral or popliteal artery and a patent tibial artery to the foot. Patients were randomized in a 2-to-1 ratio to treatment with the paclitaxel-coated balloon or conventional balloon angioplasty. Only those who had successful predilatation with an undersized standard balloon were randomized.

At 12 months, patency rates were 73.5 percent in patients randomized to the paclitaxel-coated balloon and 56.8 percent in those randomized to standard balloon angioplasty. Greater improvements in Rutherford class and walking distance scores were also observed with the paclitaxel-coated balloon.

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The benefits of the drug-coated balloon are less clear in patients with longer stenoses with moderate to heavy calcification, notes Dr. Shishehbor. “While this new technology is exciting and may help patients, questions remain, such as its efficacy, safety and cost-effectiveness for longer lesions,” he says. “In my practice, I will be using drug-coated balloons in selected patients with short lesions that have only mild to moderate calcification. In the near future, we may learn that we get better results by removing some of the plaque and then delivering the drug.”

In January, the FDA approved a second paclitaxel-coated balloon, Medtronic’s IN.PACT Admiral Drug Eluting Balloon, for treating PAD in the upper leg. Both devices are now available for routine clinical use.

Vascular brachytherapy redux

Vascular brachytherapy (VBT), which fell out of favor for the prevention of restenosis following percutaneous coronary intervention after drug-eluting stents (DESs) entered the market, is being reintroduced into practice for selected patients at Cleveland Clinic.

Stent restenosis is still a problem for some high-risk patients who receive a DES, explains Stephen Ellis, MD, Section Head of Invasive and Interventional Cardiology. The presence of diabetes, implantation of longer stents and multiple stents, and small blood vessels are risk factors that may increase the likelihood of stent restenosis.

VBT is usually considered only in patients who have experienced multiple bouts of restenosis, according to Dr. Ellis. “The approach to addressing restenosis is highly individualized,” he notes. “It includes a number of options based on the principal cause of the restenosis, the blockage size, whether the patient has restenosis in multiple spots and the number of stents the patient may already have in one area. The way the blockage comes back partly determines the likelihood that it will become a recalcitrant problem — and, to a certain extent, guides therapy.”

A standard antithrombotic regimen of aspirin and clopidogrel is used after VBT. In the short term, this regimen reduces the rate of restenosis by about 50 percent, but long-term durability of the effect in patients with a DES is not known.

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Duration of dual antiplatelet therapy after DES placement

For patients with a DES who tolerate one year of dual antiplatelet therapy with aspirin and a thienopyridine (clopidogrel or prasugrel), an additional 18 months of dual antiplatelet therapy reduces the risk of stent thrombosis and major adverse cardiovascular and cerebrovascular events compared with stopping therapy at one year.

This was the major finding of the recent international Dual Antiplatelet Therapy (DAPT) trial, in which 9,961 patients were randomly assigned to continue their thienopyridine and aspirin or to receive placebo and continue aspirin. Specifically, patients assigned to 30 months of dual antiplatelet therapy experienced the following relative to those assigned to 12 months of dual therapy:

  • 71 percent reduction in stent thromboses (P < .001)
  • 53 percent reduction in myocardial infarctions (MIs) (P < .001)
  • 29 percent reduction in risk of death, MI or stroke (P < .001)

“For patients who have tolerated dual antiplatelet therapy for one year and don’t seem to be at an excess risk for bleeding, there may be benefit to continuing for at least another 18 months,” says A. Michael Lincoff, MD, Vice Chair of the Department of Cardiovascular Medicine.

The optimal duration of dual therapy is still unknown, Dr. Lincoff adds, because the event curves were diverging until dual therapy was stopped, and an additional three months of follow-up showed that rates of stent thrombosis and MI started to increase after cessation of dual therapy at 30 months.

Although the trial was started when earlier generations of DESs were in use, the benefit of prolonged dual therapy was apparent in patients treated with newer-generation DESs.
While extended dual therapy increased the risk of moderate or severe bleeding, the benefit-to-risk ratio was still firmly on the side of extending therapy, Dr. Lincoff notes.

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