Side branching with a drug-coated balloon (DCB) led to lower major adverse cardiac events (MACE) rate at 1-year in patients with simple, true coronary bifurcation lesions than noncompliant balloons (NCBs) in the DCB-BIF study. The results — reported Monday in a late breaking session at the Transcatheter Cardiovascular Therapeutics (TCT) conference in Washington DC — are the first from a randomized clinical trial to evaluate use of DCB angioplasty for a true simple side branch (SB) during provisional stenting of a bifurcation lesion. While not recommended as standard prior to main vessel stenting — in a bid to minimize additional stenting — SB rescue stenting is often required during the provisional procedure, the study's authors noted in the Journal of the American College of Cardiology (JACC) publication, which was released simultaneously to the presentation. However, it leads to suboptimal results, the study's chair, said Shao-Liang Chen, MD, PhD, of Nanjing First Hospital, China, during his TCT presentation. Although the aim is to perform only the main vessel stenting, "Unfortunately, carina and plaque shift often lead to compression of the ostial SB with severe stenosis," the authors added. "Consequently, using a noncompliant balloon [NCB] to dilate the SB is effective to address the pinched SB. However, balloon angioplasty can easily result in SB dissection or abrupt occlusion, necessitating a second stent in the SB. In cases of in-stent restenosis, it tends to localize at the ostial SB following SB stenting, leading to stent thrombosis and repeat revascularization." The concept of "nothing left" in an SB intervention when using a DCB is therefore appealing to most cardiologists, the authors said. Yet, the benefits of DCB for coronary bifurcations remained unclear, Chen told the TCT audience. Study design The current study therefore set out to investigate whether using DCB versus NCB for the pinched SB could improve outcomes for patients with simple, true coronary bifurcations. A total 784 patients aged 18 or older with true coronary bifurcations, baseline diameter stenosis of ≥ 50% and SB stenosis of ≥70% after main vessel stenting, were treated with either DCB or NCB between September 2020 and June 2023, across 22 centers in China, Indonesia, Italy and Korea. At baseline, patients in the DCB (n = 391) and NCB (n = 393) group were of similar mean age (63.8 years vs. 63.6 years), were similarly weighted by sex (78% male vs. 75.6% male), and similar reasons for their initial presentation, with the majority of both groups having unstable angina (60.9% vs. 60.8%), followed by non-ST-elevation myocardial infarction (NSTEMI; 24.8% vs. 24.2%). However, although procedural characteristics were largely similar, Chen highlighted a statistically significant difference for kissing balloon inflation (KBI) after SB ballooning (94.9% of the DCB group vs. 98.9% of the NCB group; P value < 0.001). Exclusions included those who were intolerant to dual antiplatelet therapy (DAPT), with a life expectancy of <12 months, or with severe calcification requiring rotational atherectomy. The study noted that "The most commonly used drug coated on the balloon is paclitaxel". The researchers also said, "Our results may not be applicable to sirolimus-coating balloons, which were not used in this trial." Results The primary MACE endpoint was a composite of cardiac death, target vessel myocardial infarction or clinically driven target-lesion revascularization at the 1-year follow-up, which was completed in all patients. It occurred in 28 patients in the DCB group, and 49 patients in the NCB group (Kaplan-Meier rate: 7.2% vs 12.5%; hazard ratio [HR]: 0.56; 95% confidence interval [CI]: 0.35-0.88; P = 0.013), The result was driven primarily by a reduction in target vessel myocardial infarction (MI), which happened for 22 of the DCB group vs. 43 NCB patients (5.6% vs. 10.9%; HR: 0.50; 95% CI: 0.30-0.84; P = 0.009). However, the differences between periprocedural MI and spontaneous MI were not statistically significant. "There were no significant differences between groups in procedural success, crossover to a 2-stent approach, all-cause death, revascularization or stent thrombosis," the researchers added. Chen went on to highlight "more profound" benefits observed in subgroup analyses, for patients ≥65 years with events occurring in just over 6% of over 65s given DCB vs. 14.7% given NCB (HR: 0.39; 95% CI: 0.20-0.76), compared to under 65s, where events happened in 8.4% of the DCB group vs. 10.3% given NCB (HR: 0.82; 95% CI: 0.41-1.63). Greater benefits were also observed for those without a left main bifurcation lesion (non-LM bif) with events happening for 7.3% in DCB vs. 12.2% give NCB (HR: 0.59; 95% CI: 0.36-0.97) compared to 6.4% vs. 14.3% in the NCB group, respectively (HR: 0.44; 95% CI: 0.14-1.39). Questions unanswered Chen added that the "high rates of MI did not lead to revascularization," and that is "of unclear clinical significance". He speculated that this may be due to a lower target lesion revascularization rate among simple bifurcations. "The rapid absorption of paclitaxel into the SB vascular wall theoretically should lead to less negative remodeling and restenosis at the ostial SB, resulting in a subsequent reduction in revascularization. Unfortunately, we did not observe a reduction in either clinically driven target vessel revascularization or cardiac death with a DCB," the authors noted in the study.The researchers went on to push for further exploration of the mechanisms attributable to the reduction of MI by DCB intervention, "including the evaluation of complex bifurcation lesions that may portend more clinical significance than the simple SBs in this trial.” These results are important to note, according to an accompanying editorial, written by Ziad Ali, MD, DPhil, from the St Francis Hospital and Heart Center and New York Institute of Technology, NY, together with Celina M. Yong, MD, MBA, MSc, from the Veterans Affairs Palo Alto Healthcare System and Division of Cardiovascular Medicine and Cardiovascular Institute, CA. "In light of the recent success of DCBs in treating in-stent restenosis in the AGENT IDE (A Clinical Trial to Assess the Agent Paclitaxel Coated PTCA Balloon Catheter for the Treatment of Subjects With In-Stent Restenosis [ISR]) trial, it may seem plausible that using DCBs should be the optimal strategy for compromised side branches in simple bifurcation lesions after PCI," they said. "However, a closer look suggests that the results are not so simple and leaves several questions unanswered," including the question of why an MI would not lead to revascularization. "Three possible explanations come to mind: 1) the culprit lesion is indeterminate; 2) the lesion is not severe enough to warrant treatment; or 3) the lesion is not easily treatable," the editorialists said. Like Chen, they highlighted a "temporal disconnection" with most target-vessel MIs occurring early, and most target-lesion revascularizations happening later. "Although a sizeable portion of the MIs occurred during the periprocedural period (within 48 hours, based on the Society for Cardiovascular Angiography and Interventions definition), they clearly do not align with the timing of the post-PCI follow-up angiograms (performed a mean of 204 and 252 days after PCI in the DCB and NCB arms, respectively)," the editorialists added. "This suggests that most operators decided not to reexamine the culprit lesion after a periprocedural MI and instead managed it medically, perhaps because of the known complexity of side branch salvage with drug-eluting stents,” the editorialists concluded. Sources: Gao X, Tian N, Kan J, et al. Drug-Coated Balloon Angioplasty of the Side Branch During Provisional Stenting: The Multicenter Randomized DCB-BIF Trial. J Am Coll Cardiol 2024; DOI: 10.1016/j.jacc.2024.08.067. Ali Z, Yong C. Drug-Coated Balloons to Keep Interventions of the Side Branch Simple (KISS): KISS or Be KISS’D. J Am Coll Cardiol 2024; DOI: 10.1016/j.jacc.2024.09.020. Image Caption: Shao-Liang Chen, MD, PhD, speaks during a news conference Monday at the Transcatheter Cardiovascular Therapeutics (TCT) conference in Washington, DC. Image Credit: Bailey G. Salimes/CRTonline.org