DCBs for CAD in Certain Patients With Large Vessel De Novo Disease? DEBUT Says Yes
Intended for patients at high bleeding risk, the strategy allows for a short DAPT regimen, without a MACE trade-off and no more TLR than BMS.
PARIS, France—Patients who have a high risk of bleeding due to older age, anticoagulation, or other factors but require treatment for de novo coronary artery lesions in large vessels could be candidates for drug-coated balloons (DCBs), researchers reported today at EuroPCR.
Findings from the small, single-blind, randomized DEBUT trial show that, compared with BMS, DCBs offer such patients a lower risk of MACE at 9 months, with no uptick in TLR.
DEBUT “is the first RCT investigating the efficacy of the [drug-eluting balloon]-only strategy in large de novo coronary artery lesions,” researcher Tuomas Rissanen, MD, PhD (North Karelia Central Hospital, Joensuu, Finland), said in his presentation.
Currently, the best PCI strategy for patients at high risk of bleeding is not clear, Rissanen observed. And while there are few data on the use of DCBs in de novo lesions, he said, the possibility of shortening dual antiplatelet therapy (DAPT) duration to 1 month, or even omitting it entirely, is appealing in this patient subset.
Bruno Scheller, MD (Universität des Saarlandes, Homburg, Germany), who served as a panelist during the late-breaking session here, told TCTMD that high-bleeding-risk patients are a “complicated” population to treat. “The concept of leaving nothing behind makes a lot of sense in this indication,” he commented, agreeing that DEBUT marks the first well-conducted, randomized trial of DCB in large coronary vessels.
“It shows very clearly that you can treat not only small vessels,” where DCB use is more common, “but also large vessels without stent implantation” as long as lesion preparation is done carefully, he said.
According to Scheller, DCB use in the coronaries currently varies around the world, reaching around 3-7% of angioplasties in Germany and 20-25% in Japan, for example. European guidelines recommend DCBs for in-stent restenosis, but the majority of use is in small vessels, he added. In the United States, there are no DCBs approved for treating coronary artery disease.
“Most cardiologists say, ‘I want to sleep at night, and I need a stent to sleep at night.’ But that’s not true, because the safety of stents came with the introduction of dual antiplatelet therapy in the 90s, and these data [from DEBUT] show you have no early vessel thrombosis when using DCB according to the rules of careful predilatation and then deciding if you need to stent or not,” he said, adding that DAPT can still be “helpful in this setting.”
DCB vs BMS
Rissanen and colleagues enrolled 220 patients with either stable or unstable angina or NSTEMI along with a bleeding risk factor. All had at least one de novo lesion in a native coronary artery or bypass vein graft where the reference diameter of the vessel measured between 2.5 and 4.0 mm.
First, predilatation was done using a semicompliant, noncompliant, or cutting balloon of the nominal vessel size. After 12 patients were excluded due to flow-limiting dissection or more than 30% recoil, the remaining 208 were randomized to receive either a SeQuent Please paclitaxel-coated balloon (BBraun; n = 103) or BMS (n = 105). DAPT duration in both groups was 1 month for stable CAD and 6 months for ACS.
Baseline characteristics in the two cohorts were similar apart from diabetes, which was more common in the BMS arm. Bleeding risk factors (mainly anticoagulation and older age, but also including anemia, prior intracranial hemorrhage or stroke, active malignant disease, severe renal or liver dysfunction, frailty, prior bleeding, and potential to be noncompliant for 12 months of DAPT) also matched up well, though more patients in the DCB group were slated for elective surgery.
At 9 months, the primary endpoint of MACE (CV mortality, nonfatal MI, or TLR) was less common with DCBs compared with BMS (1.9% vs 12.4%; RR 0.15; 95% CI 0.04-0.68), a difference that met criteria for both noninferiority (P < 0.001) and superiority (P = 0.004). Adjustment for the disparity in diabetes meant that the 9-month MACE risk was sixfold higher for BMS vs DCBs when using logistic regression (P = 0.019) and twofold higher when using a Cox model (P = 0.039).
None of the DCB-treated patients underwent TLR by 9 months, as compared to 4.8% of the BMS-treated patients (P < 0.001 for noninferiority and P = 0.06 for superiority). BARC 2-5 bleeding events occurred with similar frequency in both groups. Over 9-month follow-up, there were two cases of definite stent thrombosis with BMS, but no vessel closures with DCBs.
“PCI with a drug-coated balloon with the possibility for bailout stenting is a safe and efficient novel option in these patients,” Rissanen concluded.
While awaiting novel stents as alternatives to BMS for patients at high bleeding risk who cannot take lengthy DAPT regimens, “a strategy with drug-eluting balloons still makes sense,” said panelist Antonio Colombo, MD (EMO GVM Centro Cuore Columbus, Milan, Italy), after Rissanen’s presentation. “The problem [is] many operators are uncomfortable not using a stent in a large vessel, even when they have a good result.” In cases with dissection, it’s probably too risky, he advised. “I think safety is number one. But if you have a good result, . . . why do you need to place a stent?”
Colombo suggested measuring fractional flow reserve after treatment might provide some reassurance to operators that DCBs have done the job.
“What’s next? What’s the next trial after this?” Scheller asked Rissanen, who replied: “I think we have to challenge DES in bleeding-risk patients.” But first, he continued, the DAPT protocol merits a closer look, “because I’m not sure . . . what this 1 month of DAPT is based on after drug-eluting balloon. I don’t think we need at all. We could use single antiplatelet or a loading dose alone.”
To TCTMD, Scheller described the use of BMS in DEBUT as a limitation, but said other randomized trials are on the way: PEPCAD NSTEMI, which also employs BMS but in a larger cohort, and BASKET-SMALL2, which pits DES against DCB in small coronary vessels. “There’s a lot of new stuff coming this year,” he said.
Rissanen T. Drug-eluting balloon for the treatment of de novo coronary artery lesions in patients with high bleeding risk – a randomized controlled single-blind multicenter trial (DEBUT). Presented at: EuroPCR 2018. May 23. 2018. Paris, France.
- Rissanen reports receiving research and educational grants andas well as honoraria from BBraun.