Longer Term, IN.PACT SFA Trial and Global Registry Continue to Support DCB Therapy as an Option

LAS VEGAS, NV—In patients with symptomatic peripheral arterial disease, a drug-coated balloon (DCB) shows superior efficacy at 3 years compared with plain balloon angioplasty and performs well at 1 year in the real world outside of clinical trials, according to data released today in two late-breaking presentations at VIVA 2016. 

But presenters of both studies made it clear that all DCBs for the treatment of superficial femoral popliteal artery (SFA) lesions should not be lumped together.

Presenting the 3-year trial results from the IN.PACT SFA trial, Prakash Krishnan, MD (Mount Sinai Heart, New York, NY), said “there really may not be a class effect” and that each of the DCBs need to be considered in the context of its own data. To date, the IN.PACT Admiral (Medtronic) and the Lutonix (Bard Peripheral Vascular) DCBs are US Food and Drug Administration-approved for PAD. Krishnan suggested that the IN.PACT findings support “a paradigm shift in our therapy,” such that it should be considered a first-line treatment option.

Similarly, in a press conference prior to his presentation of global registry results with the same DCB, Michael R. Jaff, DO (Massachusetts General Hospital, Boston, MA), stressed that there has not been a head-to-head trial of all the DCBs that are either approved or being tested in clinical trials.

“[T]he only thing that I tell my colleagues is we’re trying to practice on the emerging literature as it’s presented and published,” he observed, adding that looking across the trials there is “a consistent story . . . patients are actually doing quite well, and we’ve been able to expand what we’ve learned from the randomized pivotal trials to the real-world patient populations that we’re seeing. I do think a very important question . . . is the pattern of failure of drug-coated balloons over time. What can we be doing differently at the time of treatment that would give us better durability over time?”

Good Durability at 3 Years

For the IN.PACT SFA trial, 331 patients with symptomatic SFA lesions (Rutherford stages 2-4) up to 18 cm long were randomized to receive the DCB ( =n = 220) or standard angioplasty (n = 111) at 57 sites in Europe and the United States.

At 3 years, Krishnan reported that primary patency was higher in the DCB group than with angioplasty alone (69.5% vs 45.1%; P < 0.001) and clinically driven TLR was lower (15.2% vs 31.1%; P = 0.002).

The results, he added, are in line with previously reported 1- and 2-year numbers from IN.PACT SFA. The TLR advantage for the DCB “is incredibly impactful for all patients and also for the economic viability” of the procedure, Krishna noted.

Other effectiveness outcomes also were better with the DCB compared with angioplasty, including time to first clinical TLR, which was 542.9 days versus 302.9 days (P < 0.001). The same was true for sustained clinical improvement, which included freedom from amputation and TLR, as well as increases in Rutherford score.

Additionally, in terms of safety, the DCB showed an advantage for the composite of freedom from 30-day device and procedure-related death, target limb amputation, and clinically driven TLR within 36 months. There was no difference in MACE rates, but all-cause death was higher in the DCB group (10.9% vs 1.9%; P = 0.006), a finding that has been seen before in the IN.PACT trial data. According to Krishnan, a “deep dive” into these deaths shows that they occurred at a median of 1.8 years (> 600 days), and that they were “highly unlikely” to be related to the DCB itself or the procedure.

Although there were no disparities between groups at 3 years on either the 6-minute walk test or walking impairment measures, Krishnan stressed that DCB patients achieved the same level of function with 48% fewer reinterventions.

After Krishnan’s presentation, panelist Tony Das, MD (Walnut Hill Medical Center, Dallas, TX), suggested that primary patency in the overall population of patients eligible for intervention could be even higher than the 69.5% seen here if patients with more complex and longer lesions were parsed out.

The Good and Bad of the Real-World

In the second presentation, Michael R. Jaff, DO, of Massachusetts General Hospital (Boston, MA), reported that 92.6% of patients enrolled in the IN.PACT global registry had freedom from clinically driven TLR through 1 year. The rate of primary sustained clinical improvement was 80.6%. Safety also was high, with a primary safety endpoint rate of 92.1%. 

The MACE rate at 1 year was 12%, and the all-cause death rate was 3.5%.

The data come from 1,406 all-comers enrolled in 27 countries. Many would not be eligible for randomized trials, suggesting safety and effectiveness in a variety of populations, Jaff said.

Today’s findings, he added, indicate the positive results from the IN.PACT SFA trial have continued into the real-world patient population.

Of interest, Jaff reported that the rate of provisional stenting was about 24% in the global registry, leading Krishna Rocha-Singh, MD (Prairie Heart Institute, Springfield, IL), who moderated the press conference with Jaff, to raise the issue of whether the added cost of stenting or other adjuvant therapies could affect economic decisions regarding DCBs.

Jaff noted that about 65% of patients in the registry had significant calcification, with 10-12% considered severe. Lesion lengths also were long (mean > 12 cm), and treatment occurred in 64 centers of varied expertise with DCB therapy. All of those things, he said, makes the bailout stenting rate not a surprise.

“Now, will that play out from a cost-effectiveness standpoint—that is the question,” Jaff said. “What therapy is going to turn out to win the best for a health system that’s got limited money to spend on a patient with PAD for a year? I think somebody’s got to figure that out.”