BASKET-SMALL 2: Drug-Coated Balloon Fares Well Against DES for De Novo Small-Vessel Disease

MUNICH, Germany—In patients with de novo lesions in small coronary arteries, a drug-coated balloon (DCB) provides results similar to those obtained with second-generation DES after successful predilatation, according to the BASKET-SMALL 2 noninferiority trial.

In patients with diseased vessels smaller than 3 mm in diameter, the rate of MACE through 1 year was 7.33% with the SeQuent Please paclitaxel-coated balloon (B. Braun Melsungen) and 7.45% with DES, a difference that met criteria for noninferiority (P = 0.0152), Raban Jeger, MD (University Hospital Basel, Switzerland), reported here at the European Society of Cardiology (ESC) Congress 2018. Results were similar in a per-protocol analysis.

Use of the DCB was safe, with no cases of acute vessel closure and similar rates of stent thrombosis and major bleeding compared with DES.

“Small native coronary artery disease may safely be treated with DCB after successful predilatation,” Jeger concluded at a press conference. “We have a potential benefit of leaving behind an intact vessel without an armor, without a stent. Therefore, we don’t expect any thrombotic events, and no prolonged dual antiplatelet therapy is necessary. In drug-coated balloons, you just need 4 weeks of dual antiplatelet therapy.”

Any theoretical benefit of avoiding stenting in terms of very late adverse events, he added, will require long-term follow-up to prove.

Jeger cautioned, too, that “it’s a steep learning curve for this, because we need . . . the courage not to treat just the image but the vessel, and sometimes you have some recoil or some minor dissection and you just need the courage to leave that and you should not expect stent-like results.”

The findings were published simultaneously online in the Lancet.

Commenting at the press conference, ESC spokesperson Steen Dalby Kristensen, MD, DMSc (Cardiovascular Research Centre, Aarhus University, Skejby, Denmark), suggested the impact of the trial could be limited by its size and by the use in about one-quarter of patients of a DES—the Taxus Element paclitaxel-eluting stent (Boston Scientific)—that has been shown to carry higher event rates than the gold-standard Xience everolimus-eluting stent (Abbott).

“It’s a nice and interesting study, but to be frank I think it is too small to change my practice,” he said. “I would like to see more data.”

Roxana Mehran, MD (Icahn School of Medicine at Mount Sinai, New York, NY), who served as a discussant following Jeger’s presentation at a Hot Line session here, agreed that the trial is not definitive.

She highlighted several issues, including questions about the size of the vessels included in the study because of the lack of confirmation with an angiographic core lab assessment; questions about the size and number of devices used in each arm; the use of the Taxus Element stent in some of the patients; and the possibility of selection bias stemming from the long, roughly 5-year enrollment period.

“I’m not so clear if we actually are showing noninferiority because of the patients who are included in the trial,” she told TCTMD. “But I think it really sets the stage for a head-to-head evaluation of DES versus drug-coated balloons in patients with truly small-vessel, diffuse disease, because I do think there is a very important opportunity for us to treat [these] patients.”

Longer-term data are critical, too, for establishing how DCB results stand up over time, she said.

“The utility of this is not to replace DES. It’s really to treat lesions in truly small vessels where we know there’s going to be an issue with DES,” Mehran said.

Another Option for Small-Vessel Disease

DCB have been established as safe and effective options for treating in-stent restenosis in BMS or DES, but it remains unclear whether they have a role to play for de novo coronary lesions, for which DES remain the standard. In smaller vessels, though, DES are limited by the specter of in-stent restenosis, opening the door for alternative approaches.

BASKET-SMALL 2, conducted at 14 centers in Germany, Switzerland, and Austria, was an open-label, noninferiority trial that included 758 patients with de novo coronary lesions measuring 2 to less than 3 mm in diameter and an indication for PCI. After successful predilatation—resulting in no flow-limiting dissections and no residual stenosis > 30%—patients were randomized to angioplasty with the SeQuent Please balloon or one of two second-generation DES. The trial started as a comparison with the Taxus Element, but after that became unavailable, the comparator became the Xience. Dual antiplatelet therapy was given according to current guidelines: 4 weeks for DCB, 6 months for DES in non-ACS patients, and 12 months for DES-treated patients with ACS.

Most patients (about 70%) had stable angina, about 15% had NSTEMI, roughly 12% had unstable angina, and a small number of patients had STEMI.

The primary objective, which was met, was to establish the noninferiority of DCB versus DES for 1-year MACE (cardiac death, nonfatal MI, and TVR). No significant differences were seen in the individual components of the composite endpoint, although in the DCB arm cardiac deaths were numerically more frequent (3.1% vs 1.3%) and nonfatal MI (1.6% vs 3.5%) and TVR (3.4% vs 4.5%) were numerically less frequent.

The findings regarding MACE were consistent across subgroups.

“A stent-free treatment of coronary artery disease with DCB is safe if an acceptable angiographic result can be obtained after predilatation of the lesion,” Jeger and colleagues conclude in their paper. “To date, the technique is restricted to small coronary arteries, but might be expanded to larger vessel sizes with future research.”

‘A Good Option’

Deepak Bhatt, MD (Brigham and Women’s Hospital, Boston, MA), told TCTMD that the best approach for treating small vessels has been unclear, adding that DCB “seem like a good option.”

The results of BASKET-SMALL 2 should make people more comfortable with the idea of using DCB for small-vessel disease, but not necessarily as the default option, Bhatt said.

For vessels with diameters of 2.0 to 2.5 mm, DCB may be appealing, but for vessels with diameters between 2.5 and 3.0 mm, Bhatt said he’d probably stick with current-generation DES. One specific situation in which he’d strongly consider using a DCB is in a patient with a bifurcation lesion involving a 3.0-mm parent vessel and 2.0-mm branch.

“I think in that situation a drug-coated balloon would be really appealing,” he said. “I can think of concrete uses, probably not the majority of cases, but where it’s felt that small vessels need some form of revascularization where I’d rather just not put the metal in if I can help it.”

Although more data is always better, Bhatt said, there is enough information out there to suggest DCB could be a useful option.

“The drug-coated balloons in aggregate are amassing more and more data in terms of their use and their safety and potential efficacy,” he said. “In most circumstances, a drug-eluting stent probably is still going to beat it, but in certain circumstances, such as small vessels or small vessels involving bifurcations, this could be a really nice option.”

And it seems many of the attendees of Jeger’s presentation agree with that assessment. When asked in a poll about a hypothetical friend with a 2.25-mm obtuse marginal branch for which treatment with either DCB or DES is feasible after predilatation, 48% of respondents said the friend should ask for DCB, with 19% recommending a second-generation DES.