Drug-Coated Balloons-Based Intervention for Coronary Artery Disease

Abstract

Drug-coated balloons (DCBs) provide a stent-free alternative, reducing risks like stent thrombosis and in-stent restenosis and the need for prolonged dual antiplatelet therapy. Recent studies show that DCBs can be effective and safe across various coronary artery diseases (CADs) when lesions are adequately prepared. Specifically, all coronary lesions are treated using the provisional approach, where active lesion preparation is followed by DCB or drug-eluting stent treatment, depending on the results. This approach means DCB is considered the default device before initiating intervention, with efforts focused on obtaining adequate lesion preparation. Depending on the result, DCB or drug-eluting stent is selected, which is termed DCB-based percutaneous coronary intervention. Therefore, this second report of the Asia-Pacific Consensus Group provides practical guidelines (DCB-based percutaneous coronary intervention) based on the latest evidence for DCB treatment in CAD and aims to expand its application across various CADs, facilitating its effective use in real-world clinical practice.

Central Illustration

Highlights

• •DCB treatment is recommended for ISR lesions and de novo small vessel disease in CAD.
• •DCB provides an appealing option for managing various de novo coronary lesions.
• •DCB-based PCI can improve outcomes in cases with small stent burden compared with DES-only PCI.
• •Physiology- or imaging-guided PCI plays a crucial role in both DES and DCB treatment.

Recent advancements in percutaneous coronary intervention (PCI), specifically with drug-eluting stent (DES) development, have led to remarkable improvements in safety and efficacy. However, the persistent occurrence of recurrent events, including late stent thrombosis and restenosis, with an annual risk of nearly 2% without a plateau post–stent implantation, emphasize the need for alternative treatment modalities.^1,2 Despite improvements in technology, complex lesions, including multiple or diffuse lesions, particularly in small vessels, tend to yield suboptimal clinical outcomes.³ This is linked to multiple and longer stent use, which increases the risks of stent-related issues.⁴

Drug-coated balloon (DCB) introduction has heralded a new era in the treatment landscape of coronary artery disease (CAD), providing patients with an alternative or complementary option to conventional stent use.5, 6, 7 Managing CAD via DCB treatment involves the rapid and uniform transfer of antiproliferative drugs into the vessel wall during single balloon inflation, using a lipophilic matrix without requiring permanent implants.⁸ Applying a DCB ensures that no foreign bodies remain within the vessel lumen, allowing the blood vessel to naturally remodel to its original configuration.⁵ Additionally, DCB eliminates the risk of stent-associated maladaptive biological responses leading to restenosis and thrombosis and actively promotes favorable natural vascular healing and positive remodeling.^6,9, 10, 11, 12, 13 DCB treatment is currently recommended for managing in-stent restenosis (ISR) lesions originating from bare-metal stents (BMS) and DES and treating de novo small vessel disease.^14,15 The first Asia-Pacific Consensus Group recommendation and recent research have highlighted DCB treatment as a favorable option to conventional stent-based strategies across diverse CAD contexts.^6,16

In the Asia-Pacific region, patient demographics and disease characteristics vary from those observed in Europe.¹⁷ Coronary angiography shows that Asia-Pacific patients usually present with smaller coronary arteries but longer lesion lengths than Western patients.¹⁸ This coronary manifestation, characterized by “small and diffuse CAD,” may indicate the higher prevalence of diabetes mellitus among Asia-Pacific patients.¹⁹ Small-vessel CAD is typically associated with a poorer prognosis for higher restenosis, late lumen loss, and revascularization rates than large vessel CAD, mainly because of its limited capacity to accommodate neointimal growth post–stent placement.^20,21 Furthermore, accumulating evidence suggests that Asia-Pacific patients could manifest a unique risk-benefit scenario regarding antiplatelet therapy, typically characterized by diminished risk of thrombosis and elevated risk of bleeding, respectively.²² Therefore, Asia-Pacific patients with these characteristics may derive relatively greater benefits from DCB treatment, preventing the use of foreign materials and necessitating a shorter DAPT duration in CAD management than other ethnicities.

The objective of these recommendations from the consensus group is to provide Asia-Pacific patients with CAD with practical guidelines founded on the latest evidence. Furthermore, the intent is to expand the DCB treatment to encompass a broader spectrum of CAD and facilitate their efficient and appropriate application in real-world clinical settings by DES supporting DCB or through a hybrid approach.

Technical Aspect of DCB Application

Optimal lesion preparation

The success of DCB treatment requires not only resolving epicardial coronary artery stenosis but also optimizing coronary blood flow, typically accomplished through meticulous lesion preparation, commonly with balloon angioplasty (BA), to ensure sufficient myocardial perfusion. A previous study suggested that some factors, including percent diameter stenosis, intimal tear or dissection, and a pressure gradient of ≥20 mmHg, are linked to an increased risk of acute closure post-BA.²³ However, other studies have suggested that coronary dissection, when accompanied by a TIMI flow grade of 3 or uncomplicated, non–flow-limiting dissections, is associated with favorable outcomes and predicts a reduced restenosis rate.²⁴

Compared with conventional BA, which primarily resolves stenosis or creates a passage for DES, DCB is not intended for BA but for delivering a coated antiproliferative drug to the vessel wall. Therefore, optimal lesion preparation is crucial before DCB application to ensure successful local drug delivery. Bailout stenting can be prevented by selecting the final device after meticulously preparing the lesion. This preparation’s primary objectives include enhancing blood flow through induced dissection and facilitating uniform drug delivery.

The primary method for preparing lesions involves conducting conventional angioplasty using a semi-compliant or noncompliant balloon with a balloon-to-vessel ratio of 1.0 and applying inflation pressure beyond nominal levels.^6,7 In cases where balloon delivery difficulties, vessel underfilling, or potential undersizing are expected, starting the procedure with a smaller balloon followed by reevaluating the vessel size after administering vasodilators might be advisable.⁷ Subsequently, with improved flow, selecting the next balloon that matches the vessel size is necessary. In situations involving complex lesions, different strategies may be required, including using noncompliant high-pressure balloons, scoring or cutting balloons, or considering advanced procedures (including rotablation, orbital or directional atherectomy, or intravascular lithotripsy). These devices are associated with a lower risk of severe dissection and a higher incidence of optimal angiographic outcomes than conventional semicompliant balloons.25, 26, 27 Intravascular imaging techniques (including intravascular ultrasound [IVUS] or optical coherence tomography [OCT]) or functional assessments (fractional flow reserve [FFR] or instantaneous wave-free ratio) can provide valuable insights into treatment optimization.^25,28,29 Recently, the ULTIMATE-III (Intravascular Ultrasound Versus Angiography Guided Drug-coated Balloon) trial comparing IVUS- and angiography-guided DCB treatments for coronary de novo lesions in high-bleeding risk patients demonstrated that IVUS-guided DCB treatment is associated with a lower late lumen loss at 7 months follow-up than angiography guidance.³⁰

Although all coronary lesions could potentially be candidates for DCB treatment, lesions that fail to achieve optimal lesion preparation may represent a contraindication for DCB use. The following 2 criteria must be met after lesion preparation before applying a DCB: achieving TIMI flow grade 3 without flow-limiting dissection and ensuring that residual stenosis is ≤30% (as shown in the Central Illustration).^6,7 When conducting angiography, confirming the complete absence of delayed contrast clearance, not only from the vessel lumen and its walls but also from any potential dissection planes, is essential. Recent data have demonstrated that most non–flow-limiting dissections, classified as less than type C, underwent a benign healing process post-DCB treatment, usually resulting in positive remodeling during follow-up.^9,10,31 Although the long-term effects of antiproliferative drugs on the dissection degree remain unknown, current evidence suggests that long-term vascular remodeling varies depending on the dissection extent.^25,32 Notably, the presence of dissections extending into the tunica media tends to lead to greater lumen expansion, particularly when the flow is sustained.³³ Post-DCB use, a final assessment was conducted at least 5 minutes after administering an intracoronary vasodilator bolus to prevent any residual acute vessel closure.

Central Illustration.

Drug-Coated Balloon–Based Treatment Approach for Coronary Artery Disease

Drug-coated balloon (DCB)–based percutaneous coronary intervention prioritizes optimal lesion preparation, using DCB as the default device and deciding between DCB or drug-eluting stent (DES) based on outcomes. This approach minimized stent use, ensuring effective drug delivery and reducing the need for bailout stenting. FFR = fractional flow reserve.

FFR-guided DCB treatment

FFR application post-BA in larger vessels helps determine whether a DCB or DES is the preferred treatment for the lesion. In de novo large vessel disease cases, FFR-guided DCB treatment is a crucial tool for preventing acute ischemic events immediately after the procedure, including acute recoil and severe dissection. When the post-BA FFR value suggests DCB suitability (cutoff FFR ≥0.75), it ensures a favorable outcome with adequate anatomical and physiological patency during follow-up examinations (Supplemental Figure 1).²⁸ Furthermore, FFR-guided DCB treatment demonstrated sustained anatomical and physiological patency, along with plaque redistribution and vessel remodeling, without acute vessel closure, chronic elastic recoil, or restenosis throughout the follow-up.^11,12 Although no validated data exist to define the optimal FFR threshold post-BA, current consensus suggests a threshold of 0.75 as a reasonable compromise based on clinical efficacy.⁶ An alternative for functional assessment after lesion preparation can be angiography-guided physiology, such as quantitative flow ratio. However, although postprocedural quantitative flow ratio gradient was an independent predictor of target lesion revascularization (TLR) in the DCB treatment,³⁴ further evidence and studies are required to clarify its role in this context.

Although coronary physiology aids in step-by-step flow assessment during PCI, integrating intravascular imaging and physiology can enhance procedural outcomes. IVUS or OCT is essential for assessing plaque composition, ensuring adequate lesion preparation, and optimizing vessel sizing to minimize complications such as dissections.³⁵ Specifically, residual dissections have been linked to positive vessel remodeling at follow-up and intravascular imaging use and over-reaction should not lead to an overestimation of bail-out stenting to seal non–flow-limiting dissections (Supplemental Figure 1).^36,37 Therefore, emerging technologies like optical and ultrasonic flow ratios show promise for advancing DCB treatment guidance and optimization.

Local drug delivery optimization

Considering a DCB application is warranted when the angiographic results meet the criteria. Geographic miss refers to the situation where the drug delivery does not adequately cover the entire length of the targeted lesion or the adjacent reference segments.⁶ This can result from improper positioning of the balloon during inflation, leading to incomplete treatment of diseased areas or exposing healthy vessel segments to unnecessary drug delivery. Like with DES, geographic miss has been identified as an independent predictor of restenosis in DCB treatment.^38,39 To avoid geographic mismatch, the angle that best shows the lesion is displayed on the screen as a roadmap, and the procedure is continued from that view. Furthermore, the DCB must extend at least 2 to 3 mm beyond the predilated segment on both sides. Ensuring accurate sizing is essential, and OCT can help overcome the underestimation associated with angiography and the overestimation observed with IVUS, especially in small vessels.⁴⁰ The DCB diameter should match the target vessel diameter, adhering to the recommended balloon-to-vessel ratio of 1.0. Additionally, maintaining the DCB inflation for at least 60 seconds at nominal pressure ensures sufficient drug delivery to the vascular wall and reduces the risk of additional dissection or the need for bailout stenting.41, 42, 43 However, if a patient cannot tolerate an extended inflation duration, a shorter inflation time (eg, 30 seconds) may be acceptable. Understanding that DCB is primarily aimed at drug delivery rather than solely addressing vessel stenosis as in traditional BA is essential. According to the manufacturer’s guidelines, the DCB should reach the lesion within 2 minutes of vascular access to ensure expedited delivery whenever feasible. However, prolonged drug exposure to the aqueous environment (with an inflation delay >25 seconds) or insufficient contact time with the target lesion (total inflation time <60 seconds) may increase target lesion failure (TLF) risk by approximately 2.0-fold each.⁴¹ Therefore, proper procedural optimization achievement should be continuously assessed from the initial decision to the DCB procedure completion.

DCB-based PCI

DCB-based PCI is a procedure where DCB is employed as the first-choice default device for all coronary lesions, aimed at achieving optimal lesion preparation (Central Illustration). The decision to use a DCB or DES is based on the lesion preparation outcomes. This strategy underlines the critical role of optimal lesion preparation before deciding on the final treatment device, either a DCB or DES. Compared with conventional stent implantation, which uses predilation to facilitate stent placement, DCB treatment mandates adequate lesion preparation to maximize luminal gain, ensure sufficient coronary blood flow, and effectively deliver antiproliferative drugs to the vessel wall. This DCB-based approach reduces the overall use of stents and helps prevent the need for bailout stenting post-DCB treatment.

Recent studies suggest that a strategy to reduce stent use can enhance clinical outcomes compared with the traditional DES-alone approach, particularly in patients with multivessel CAD.^44,45 When lesion preparation is inadequate or flow-limiting dissection occurs, switching to DES implantation is viewed as a provisional adjustment to manage significant residual stenosis or flow-limiting dissections rather than as a bailout. This approach, highly feasible in real practice, can be applied regardless of various lesion characteristics and clinical presentations based on the lesion preparation results.

DCB Application According to Lesion Characteristics

In-stent restenosis

ISR treatment remains a significant clinical challenge despite advancements in newer-generation DES with improved performance. Historically, whether conventional BA or the stent-in-stent approach is more effective for managing ISR has been considerably debated. Previous trials have demonstrated that treating BMS- and DES-ISR with BA or first-generation DES leads to high revascularization rates and increased long-term risk of stent thrombosis compared with DCB treatment.^46,47 Subsequent research, including the RIBS (Restenosis Intra-Stent of Bare Metal Stents: Paclitaxel-coated Balloon vs Everolimus-eluting Stent) V trial, has compared the efficacy of DCB and second-generation DES in patients with BMS-ISR.⁴⁸ Although late angiographic findings favored the DES group over the DCB group, similar rates of restenosis and clinical outcomes were observed in both groups. Although the RIBS IV trial favored second-generation DES over DCB in treating DES-ISR,⁴⁹ the more recent DARE (Drug-Eluting Balloon for In-Stent Restenosis) trial demonstrated that DCB is comparable to second-generation DES in terms of 6-month minimal lumen diameter and target vessel revascularization (TVR) up to 1 year in patients with any ISR type.⁵⁰

Evidence from previous trials shows that DCB is superior to BA alone and is comparable to first-generation DES in clinical outcomes for patients with both BMS- and DES-ISR. The recent ESC guidelines on chronic coronary syndrome recommend both DCB and DES as potential treatments for DES ISR but identify DES as the preferred strategy over DCB.⁵¹ DCB treatment outcomes for BMS- and DES-ISR may vary caused by differences in restenotic tissue and original stent characteristics.^52,53 However, DCB is preferred for ISR lesions when adequate lesion preparation is achieved post-BA, as it delivers antirestenotic drugs without adding extra stent layers, which is particularly beneficial in DES-ISR. Although new-generation DES stents may slightly reduce the need for TLR in the ISR lesions,⁵⁴ the risk of additional stent layers makes DCB the preferred choice for BMS- and DES-ISR when angiographic outcomes post-BA are favorable.

Additionally, the use of intravascular imaging modalities, including IVUS and OCT, is recommended to identify the morphological causes of ISR, which helps in achieving optimal lesion preparation, satisfactory angiographic outcomes, and successful drug delivery.

De novo lesion

Small vessel disease

Coronary small vessel disease, characterized by CAD affecting vessels with a diameter <3 mm poses a significant challenge in coronary revascularization. This is caused by increased risks of restenosis and stent thrombosis post-DES implantation.^55,56 However, DCB treatment shows notable potential in small vessel disease, as the percentage of lumen loss post-stent placement constitutes a larger portion of the total lumen diameter in small vessels than in larger ones. In the randomized BASKET-SMALL (Basel Kosten Effektivitäts Studie-Drug-Coated Balloons in Small Coronary Artery Lesions) 2 trial, DCB treatment proved as effective as second-generation DES for treating de novo small vessel disease. Over a 3-year follow-up, both groups showed comparable rates of major adverse cardiac events (MACE).¹⁵ Additionally, results from the PICCOLETO (Drug Eluting Balloon Efficacy for Small Coronary Vessel Disease Treatment) II trial, which targeted patients with small vessel disease, demonstrated that DCB treatment exhibited superiority over DES (everolimus-eluting stent). Specifically, DCB showed significantly lower late lumen loss than DES.⁵⁷ A recent comprehensive meta-analysis of 29 randomized controlled trials (RCTs) involving 8,074 patients with small vessel CAD concluded that the clinical outcomes between DCB and newer-generation DES did not significantly differ.⁵⁸ Therefore, DCB treatment shows comparable efficacy to second-generation DES in managing de novo small vessel disease, with potential superiority in reducing late lumen loss compared to DES (Table 1).

Table 1.

Summary of Clinical Trials of DCB on Treatment of De Novo Coronary Lesions

Trial Name or First Author Design	Treatment	n	Angiographic Follow-up	Clinical Follow-up
Small vessel disease
BASKET-SMALL 215/RCT	DCB (Sequent Please) vs DES (Xience or Taxus Element)	382 vs 376	-	MACE: 15% (DCB) vs 15% (DES), HR: 0.99; P = 0.95 at 3 y
PICCOLETO II57/RCT	DCB (Elutax SV) vs DES-E	118 vs 114	LLL: 0.04 mm (DCB) vs 0.17 mm (DES); P = 0.001 for noninferiority; P = 0.03 for superiority at 6 mo	MACE: 6% (DCB) vs 8% (DES); P = 0.55 at 12 mo
Large vessel disease
Shin et al28/registry-observational	DCB (Sequent Please) vs BMS (Vision) or DES (Resolute Integrity or Xience Prime)	45 vs 22	LLL: 0.05 ± 0.27 mm (DCB) vs 0.40 ± 0.54 mm (Stent); P = 0.022; FFR: 0.85 ± 0.08 mm (DCB) vs 0.85 ± 0.05 mm (Stent); P = 0.973 at 9 mo	-
Her et al9/registry-observational	DCB (nonsmall) (Sequent Please) vs DCB (small) (Sequent Please)	100 vs 127	LLL: 0.03 ± 0.22 mm (nonsmall) vs 0.06 ± 0.25 mm (small); P = 0.384 at 6 mo	TVF: 7% (nonsmall) vs 8% (small); P = 0.596 at 6 mo
Gitto et al64/registry-PS matched	DCB-based (Magic Touch or Selution or IN.PACT Falcon or RESTORE) vs DES (contemporary)	147 vs 701		TLF: 4.1% (DCB-based) vs 9.8% (DES); P = 0.148 at 2 y
Lin et al65/meta-analysis	DCB vs DES	152 vs 169	LLL: SMD: −0.07; P = 0.548 at 6-9 mo	TLR: RR: 1.17; P = 0.746 at 6-9 mo
REC-CAGEFREE I66/RCT	DCB (Swide) vs DES-S	1,133 vs 1,139		DoCE: 6.4% (DCB) vs 3.4% (DES); P = 0.0008 at 2 y
Bifurcation disease
PEPCAD-BIF68/RCT	DCB (Sequent Please) vs POBA in SB	32 vs 32	Restenosis: 6% (DCB) vs 26% (POBA); P = 0.045; LLL: 0.13 mm (DCB) vs 0.51 mm (POBA); P = 0.013 at 9 mo	TLR: n = 1 (DCB) vs n = 3 (POBA)
DCB-BIF70/RCT	DCB (Paclitaxel-coated balloon) vs POBA (NCB) in SB	391 vs 393		MACE: 7.2% (DCB) vs 12.5% (POBA); P = 0.013 at 1 y
Her et al/registry-observational71	DCB (only MV) (Sequent Please)	16 MBs/32 SBs	SB os lumen area: 0.92 ± 0.68 mm2 (pre) vs 1.03 ± 0.77 mm2 (post) vs 1.42 ± 1.18 mm2 (at 9 mo)	-
Pan et al72/registry-PS matched	DCB (Sequent Please) + DES vs DES-only (new-generation)	199 vs 398	LLL: 0.13 ± 0.42 mm (DCB) vs 0.42 ± 0.62 mm (DES); P < 0.001 at 1 y	TLF: 7.56% (DCB) vs 14.36% (DES), log-rank P = 0.024 at 2 y; TLR: 2.91% (DCB) vs 9.42% (DES); P = 0.007
Chronic total occlusion lesion
PEPCAD-CTO77/registry-variable matching	DCB (Sequent Please) + BMS (Coroflex Blue) vs DES-P	48 vs 48	LLL: 0.64 ± 0.69 mm (DCB) vs 0.43 ± 0.64 mm (DES); P = 0.14; Restenosis: 28% (DCB) vs 21% (DES); P = 0.44 at 6 mo	MACE: 15% (DCB) vs 19% (DES); P = 0.58 at 12 mo
Shin et al79/registry-PS matched	DCB-based (Sequent Please) vs DES-only (2nd generation)	200 vs 661		MACE: 3.1% (DCB) vs 13.2% (DES); P = 0.001 at 2 y
Diffuse long and multivessel disease
Costopoulos et al80/registry-variable matching	DCB (IN.PACT Falcon + Pantera Lux) ± DES vs DES (2nd generation)	93 vs 93	-	MACE: 21% (DCB) vs 23% (DES); P = 0.74; TVR: 15% (DCB) vs 12% (DES); P = 0.44; TLR: 10% (DCB) vs 9% (DES); P = 0.84 at 2 y
Yang et al81/registry-observational	DCB (Sequent Please) ± DES (new-generation) vs DES (new-generation)	360 vs 831	LLL: 0.06 ± 0.61 mm (DCB) vs 0.41 ± 0.64 mm (DES); P < 0.001; MLD: 1.74 ± 0.59 mm (DCB) vs 1.94 ± 0.65 mm (DES); P = 0.002 at 9-12 mo	TLR: 7% (DCB) vs 8% (DES), log-rank P = 0.636; MACE: 11% (DCB) vs 14% (DES), log-rank P = 0.324; Thrombosis: 0 (DCB) vs 1% (DCB), log-rank P = 0.193 at 3 y
Shin et al44/registry-PS matched	DCB-based (Sequent Please) vs DES (2nd generation)	254 vs 254	-	MACE: 4% (DCB) vs 11% (DES); P = 0.002 at 2 y

BMS = bare-metal stent; DCB = drug-coated balloon; DES = drug-eluting stent; DES-E = everolimus drug-eluting stent; DES-P = paclitaxel drug-eluting stents; DES-S = sirolimus drug-eluting stent; DoCE = device-oriented composite endpoint; FFR = fractional flow reserve; LLL = late lumen loss; MACE = major adverse cardiac events; MLD = minimal lumen diameter; MV = main vessel; NCB = noncompliant balloon; POBA = plain old balloon angioplasty; PS = propensity score; RCT = randomized controlled trial; SB = side-branch; SMD = standard mean deviation; TLF = target lesion failure; TLR = target lesion revascularization; TVF = target vessel failure; TVR = target vessel revascularization.

Large vessel disease

Given the favorable outcomes of DCB treatment in small vessel disease, increasing evidence supports its efficacy and safety in treating de novo lesions in large coronary vessels (≥3.0 mm) (Table 1).⁵⁹ When residual dissections and limited acute luminal gain persist post-predilation, FFR application can provide a more precise assessment of functional results. Recent studies conducted in Korea have shown that FFR-guided DCB treatment is safe and effective for managing de novo lesions in large coronary vessels, including in individuals with acute coronary syndrome.^28,60 Favorable anatomical and physiological outcomes were observed during the 9-month follow-up. Notably, DCB treatment led to significantly lower late lumen loss than DES treatment, with no difference in FFR values between the 2 groups. The authors suggest that DCB treatment enhances coronary blood flow restoration by modifying plaque, resulting in a gradual enlargement of the minimal lumen area, as demonstrated by intravascular imaging techniques, including IVUS or OCT.^11,12,61,62 Additional evidence from Europe has demonstrated that using FFR-guided DCB-alone strategy is feasible and well-tolerated for treating stable CAD. This approach results in positive remodeling without compromising lumen integrity, as confirmed by OCT findings during the 6-month follow-up.⁶³

Recent studies have indicated that DCB treatment is equally effective and safe for managing de novo lesions in nonsmall and small coronary vessels.⁹ Her et al⁹ demonstrated that the target vessel failure rate did not significantly differ between the 2 groups over a 3.4-year follow-up. In another recent study focusing on lesions of the left anterior descending artery, Gitto et al⁶⁴ found that DCB-based treatment for left anterior descending lesions was safe, with acceptable rates of adverse events at the 2-year follow-up compared with contemporary DES-based treatment. DCB-based treatment was found to be associated with a lower risk of TLF than DES-alone–based PCI, mainly attributable to a reduction in TLR rates. Furthermore, a recent meta-analysis indicated that DCB treatment showed comparable efficacy to DES implantation in treating de novo large coronary lesions, with similar rates of TLR observed at the 6- to 9-month follow-up.⁶⁵ This suggests that DCB treatment for large coronary vessel disease leads to sustained favorable anatomical patency, vascular healing, and promising long-term clinical outcomes.

In the most recent randomized trial comparing DCB and DES for large vessel disease, the REC-CAGEFREE I (Drug-Coated Balloon Angioplasty With Rescue Stenting Versus Intended Stenting for the Treatment Oo Patients With De Novo Coronary Artery Lesions) trial, it was found that in patients with de novo, noncomplex coronary artery disease, regardless of vessel diameter, a DCB treatment with rescue stenting failed to demonstrate noninferiority to DES implantation in terms of device-oriented composite endpoint (DoCE) at 2 years.⁶⁶ While this study demonstrated a significant interaction between reference vessel diameter and DoCE occurrence, the final conclusions should ideally await the results of ongoing studies, such as the REVERSE (Randomized Trial of Drug-Coated Balloon Versus Drug-Eluting Stent for Clinical Outcomes in Patients With Large Coronary Artery Disease; NCT05846893), and future researches in this area. The REVERSE trial is currently evaluating the safety and effectiveness of DCB compared with DES for large vessel disease (≥3.0 mm), with results expected to provide valuable insights into clinical outcomes in de novo large vessel CAD.

Bifurcation lesion

Long-term clinical outcomes for patients with coronary bifurcation lesions usually show unfavorable outcomes, marked by an increased risk of cardiac death, myocardial infarction (MI), and the need for revascularization in the main vessel and side-branch.^6,7,67 According to findings from the PEPCAD-BIF (Paclitaxel-Eluting Percutaneous Coronary Angioplasty-Balloon Catheter versus Conventional Balloon Angioplasty For Coronary Bifurcations) trial and a meta-analysis, the DCB group exhibited a significantly lower restenosis rate than the BA group, particularly when the side-branch was treated with DCB (Table 1).^68,69 The recent DCB-BIF (Comparison of Noncompliant Balloon With Drug-Coated Balloon Angioplasties for Side Branch After Provisional Stenting for Patients With True Coronary Bifurcation Lesions) trial showed that in patients with true coronary bifurcation lesions undergoing provisional stenting, main vessel stenting combined with a DCB for the compromised side-branch resulted in a lower 1-year composite outcome rate compared to a noncompliant balloon.⁷⁰ The Korean OCT study, focusing on cases where only the main vessel underwent a DCB-alone treatment approach, supported DCB treatment safety for bifurcation lesions.⁷¹ Although the side-branch was not directly treated, the study observed an increase in the lumen area at the side-branch ostium after 9-month follow-up. Regarding left main bifurcation lesions, the latest study demonstrated that applying a hybrid strategy combining DCB and DES yielded favorable outcomes, particularly in terms of late lumen loss and TLF, compared to a DES-alone approach (provisional stenting or two-stent strategies).⁷² DES-alone–treated patients had a significantly higher late lumen loss at 1 year than patients in the DCB group. Furthermore, the DCB group exhibited a lower TLF incidence within 2 years than the DES group. Recent studies suggest that DCB treatment post–coronary atherectomy for bifurcation lesions, including those in the left main coronary artery, could reduce the need for stents, eliminate complex stent placement techniques, and lead to favorable clinical outcomes.^27,73 Particularly in bifurcation lesions, DCB treatment shows promising outcomes, including low restenosis rates, improved side-branch lumen area, and favorable clinical results compared with conventional approaches, such as DES-alone strategies.^72,74 Although the optimal strategy and specific role of DCB treatment in bifurcation diseases remain unclear, DCB is gradually being recognized as a possible alternative option for managing bifurcation lesions.

The initial step involves predilating the main vessel and/or side-branch using conventional balloons with a balloon-to-vessel ratio of 0.9 to 1.0 and an inflation pressure higher than nominal (Figure 1). DCB application to the side-branch is feasible if no flow-limiting dissection occurs and residual stenosis is ≤30% in the main vessel and ≤70% in the side-branch with TIMI flow grade 3. The DCB should extend 4 to 5 mm into the main vessel and 2 to 3 mm distally beyond the predilated area, using a DCB-to-vessel ratio of 0.9 to 1.0 for at least 60 seconds. Subsequently, DCB can be similarly applied to the main vessel, extending the balloon-covered length 2 to 3 mm beyond both sides of the predilated area. However, in cases of suboptimal lesion preparation, if the result remains unsatisfactory despite additional lesion preparation, deploying a DES in the main vessel and performing provisional stenting in the side-branch may be considered. Alternatively, employing a DES in the main vessel while adopting a DCB-alone approach in the side-branch may be considered reasonable and has shown efficacy based on prior evidence, although further scientific evaluations are needed.

Figure 1.

DCB Treatment Approach for True Bifurcation Lesion

The procedure involves predilating vessels with a balloon-to-vessel ratio of 0.9 to 1.0 and applying drug-coated balloon (DCB) if flow-limiting dissection is absent and residual stenosis meets criteria in main vessel and/or side-branch. DCB should cover the predilated area with appropriate overlap, but if results are unsatisfactory, drug-eluting stent (DES) implantation in the main vessel and/or side-branch may be considered. MV = main vessel; SB = side branch.

Chronic total occlusion lesion

Chronic total occlusion (CTO) presents substantial technical challenges during PCI, particularly in accurately sizing stents post-BA. This challenge usually leads to underestimated stent dimensions and the risk of late stent malapposition. Furthermore, adopting a “full-metal jacket” PCI approach involving overlapping DES has been associated with an increased incidence of adverse events.⁷⁵ Previous research on “full-metal jacket” PCI identified the number of DES in the target vessel and the presence of persistent distal luminal narrowing as 2 significant predictors of TLF.⁷⁶ The PEPCAD CTO (Percutaneous Transluminal Coronary Angioplasty-Balloon Catheter in Coronary Artery Disease to Treat Chronic Total Occlusions) trial reported no significant differences in angiographic findings and clinical outcomes between the BMS+DCB- and DES-treated groups (Table 1).⁷⁷ A recent study also showed that employing a DCB-alone approach without stenting was feasible and well-tolerated for treating CTO lesions, particularly when satisfactory outcomes were achieved with predilation.⁷⁸ Using a DCB-based treatment strategy (either alone or combined with DES) presents promising opportunities for effectively managing such lesions.⁷⁹ Specifically, the DCB-based treatment strategy was used to treat a CTO lesion, showing that with adequate lesion preparation, DCB treatment can be safely applied, provided TIMI flow grade 3 and residual stenosis ≤50% are achieved (Figure 2). However, in cases where lesion preparation is performed using a subintimal approach, the safety and clinical evidence supporting the use of DCB remain uncertain. Therefore, in such cases, DES implantation should be recommended to ensure optimal flow and durable long-term outcomes.

Figure 2.

DCB Treatment Approach for Chronic Total Occlusion Lesion

The DCB-based strategy effectively treats CTO lesions with adequate preparation and TIMI flow grade 3 and the residual diameter stenosis ≤50%, but DES is preferred if a subintimal approach is used, even if criteria are met. Abbreviations as in Figure 1.

Diffuse long and multivessel diseases

In situations involving diffuse long and multivessel lesions and those with a high burden of stents, the deployment of multiple lengthy metallic devices within coronary arteries may impair the restoration of vasomotion in the treated segment.⁶ This compromise can cause stent-related complications, including ISR, stent thrombosis, and neoatherosclerosis, potentially affecting the feasibility of subsequent CABG surgery. A retrospective analysis comparing the management of diffuse lesions (>25 mm) included patients treated with a DCB alone or combined with DES and those treated with DES alone.⁸⁰ At the 2-year follow-up, no significant differences in clinical outcomes were found between the DCB strategy or DES-alone approach. Another observational study focusing on lesions longer than 25 mm showed that the long-term efficacy and safety outcomes associated with the DCB strategy, either alone or combined with DES, were comparable to the DES-alone approach in diffuse coronary lesions. This conclusion was supported by similar rates of TLR and MACE observed during the 3-year follow-up.⁸¹ Shin et al⁴⁴ investigated multivessel CAD and reported that adopting a DCB-based strategy, either alone or combined with DES, substantially reduced the stent burden (Table 1). Furthermore, this approach resulted in a significantly lower MACE incidence than DES-alone treatment during the 2-year follow-up.⁴⁴ These findings suggest that using a DCB-based treatment strategy for diffuse long and multivessel diseases effectively reduces the stent burden, particularly in small vessel lesions, and shows potential for improving long-term outcomes by decreasing stent-related complications.

For diffuse long and multivessel diseases, the PCI target lesions are first determined, followed by BA to assess suitability for DCB treatment. Specifically, predilation with a semicompliant or noncompliant balloon at a balloon-to-vessel ratio of 1.0 is mandatory. Post-BA, stenting is deferred for all types of dissections (A to E), provided TIMI flow grade 3 is achieved. PCI with stent implantation without DCB use is recommended in cases of flow-limiting dissection post-predilation (TIMI flow grade <3) and residual diameter stenosis >30%. However, in exceptional cases with normal flow (TIMI flow grade 3) and residual diameter stenosis ≤30%, the operator may opt to use DES or DCB if the patient complains of new-onset chest pain post-BA or if ST-segment changes or progression of dissection is evident.⁴⁴ The DCB was inflated to its nominal pressure for at least 60 seconds, ensuring it covered the full length of the lesions dilated with predilatation balloons.

Drug-Coated Balloon Application According to Patients’ Characteristics

High-bleeding risk patients

Post-PCI bleeding is associated with higher mortality rates and can lead to additional complications, including MI and prolonged hospital stays, underscoring the importance of preventive strategies.^7,82 Despite the shorter DAPT duration required post–new-generation DES implantation than post–old-generation stent, the possibility of discontinuing antiplatelet agents may arise sooner post-DCB treatment, particularly in cases of severe, life-threatening bleeding than DES implantation. The DEBUT (Drug-Coated Balloon for Treatment of De-Novo Coronary Artery Lesions in Patients With High Bleeding Risk) trial demonstrated that DCB treatment was superior to BMS in high-bleeding risk patients, showing significantly lower rates of MACE during the 9-month follow-up (Table 2).⁸³ High-bleeding risk patients have shown superior efficacy in angiographic and physiologic patencies during the 9-month follow-up with FFR-guided DCB treatment, requiring only 1 month of DAPT, compared with BMS.⁸⁴ Recent studies show no significant difference in thrombotic event rates between single antiplatelet agent after DCB and standard antiplatelet regimens, with lower major bleeding rates.^85,86 These results suggest it could be a preferred option for this patient subgroup. Therefore, for high-bleeding risk patients, DCB treatment presents advantages over stent implantation, indicating a need for future comparisons with newer-generation DES.

Table 2.

Summary of Clinical Trials of DCB on Treatment According to Clinical Characteristics

Trial Name or First Author Design	Treatment	N	Angiographic Follow-up	Clinical Follow-up
High bleeding risk
DEBUT83/RCT	DCB (Sequent Please) vs BMS (Integrity)	102 vs 106	-	MACE: 1% vs 14%; RR: 0.07; P < 0.00001 for noninferiority; P = 0.00034 for superiority at 9 mo
Shin et al84/RCT	DCB (Sequent Please) vs BMS (Vision)	20 vs 20	LLL: 0.2 ± 0.3 mm (DCB) vs 1.2 ± 0.8 mm (DES); P < 0.001; Restenosis: 0 (DCB) vs 25% (DES); P = 0.049; FFR: 0.87 ± 0.06 (DCB) vs 0.89 ± 0.06 (DES); P = 0.254 at 9 mo	TVR: 0 (DCB) vs 15% (BMS) at 12 mo
Diabetes mellitus
DEAR89/Retrospective head-to-head comparison	DCB (DIOR) ± BMS vs BMS vs DES (Cypher, Taxus, Endeavor, Biodegradable Paclitaxel Eluting stent)	92 vs 96 vs 129	-	MACE: 13% (DCB) vs 32% (BMS); P = 0.003; 19% (DES); P = 0.29; TVF: 11% (DCB) vs 30% (BMS); P = 0.003; 19% (DES); P = 0.13 at 12 mo
BASKET-SMALL 290/RCT	DCB (Sequent Please) vs DES (Xience or Taxus Element)	122 vs 130	-	MACE: 19% (DCB) vs 22% (DES); HR: 0.82; P = 0.51; TVR: 9% (DCB) vs 15% (DES); HR: 0.40; P = 0.036 at 3 y
Her et al45/Registry-PS matched	DCB-based (Sequent Please) vs DES-only (2nd generation)	104 vs 115		MACE: 2.9% (DCB) vs 13.9% (DES), log-rank P = 0.003; Cardiac death: 0% (DCB) vs 3.5% (DES), log-rank P = 0.044 at 2 y
Acute myocardial infarction
REVELATION93/RCT	DCB (Pantera Lux) vs DES (Orsiro)	60 vs 60	FFR: 0.92 ± 0.05 (DCB) vs 0.91 ± 0.06 (DES); P = 0.27; LLL: 0.05 mm (DCB) vs 0.00 mm (DES); P = 0.51 at 9 mo	MACE: 3% (DCB) vs 2% (DES); P = 1.00 at 9 mo
PEPCAD NSTEMI94/RCT	DCB (Sequent Please and Sequent Please Neo) vs BMS or DES (new-generation limus-eluting)	104 vs 106	TLF: 4% (DCB) vs 7% (Stent); P = 0.53 at 9 mo	MACE: 7% (DCB) vs 14% (DES); P = 0.11 at 9 mo

Abbreviations as in Table 1.

Diabetes mellitus

Patients with diabetes are well-known to be at an increased risk of cardiovascular-related events, usually presenting with extensive diffuse disease necessitating longer and smaller stents compared to those without diabetes.⁸⁷ Furthermore, they typically experience poorer outcomes post-PCI, including higher incidences of ISR, stent thrombosis, MI, and mortality, than patients without diabetes.⁸⁸ The previous trial showed that patients with diabetes treated with DCB followed by BMS had significantly better outcomes than those treated with BMS alone, and their results were comparable to those of DES-treated patients.⁸⁹ Moreover, a recent subgroup analysis of the BASKET-SMALL 2 trial demonstrated that DCB treatment was noninferior to DES and showed a significantly lower TVR rate than DES in patients with diabetes.⁹⁰ In a recent Korean study, Her et al⁴⁵ demonstrated that among individuals with multivessel CAD, the clinical benefits of using a DCB-based revascularization strategy (either alone or combined with DES) appear to be more significant in patients with diabetes than in those without diabetes during the 2-year follow-up (Table 2). Furthermore, the DCB-based treatment group exhibited a significantly lower MACE risk in patients with diabetes than the DES-only group, whereas this risk reduction was not observed in nondiabetic patients. These findings suggest that adopting a DCB-based PCI strategy, particularly in patients with diabetes, substantially reduces the MACE risk compared with conventional treatments involving DES alone. Although additional data and further analyses are necessary, DCB treatment might represent a favorable option compared with DES implantation for patients with diabetes.

Acute MI

Acute myocardial infarction (AMI), being the typical example of atherothrombotic lesions, has made significant strides in reducing repeat revascularization needs with stent placement. However, patients with AMI still encounter ongoing risks of stent thrombosis and ISR.⁹¹ Therefore, DCB treatment could be considered an alternative therapeutic approach for AMI, particularly when the coronary flow is restored and residual stenosis is minimal post-thrombus aspiration and balloon dilation.^6,92 In the randomized REVELATION (Revascularization with Paclitaxel-Coated Balloon Angioplasty Versus Drug-Eluting Stent in Acute Myocardial Infarction) trial, DCB treatment demonstrated noninferiority to DES in terms of FFR during the 9-month follow-up (Table 2).⁹³ These findings suggest that DCB treatment could be a safe and effective approach for treating ST-segment elevation myocardial infarction (STEMI), provided that the culprit lesion is sufficiently prepared. In patients with non-STEMI, Scheller et al⁹⁴ demonstrated that DCB treatment was noninferior to stenting with BMS or DES. A recent meta-analysis also indicated the feasibility of DCB treatment compared to DES implantation.⁹⁵ The clinical safety and angiographic efficacy of DCB treatment were validated across a spectrum of adverse cardiovascular-related events, including MACE, cardiac mortality, all-cause mortality, MI, bleeding events, TVR, TLR, and late lumen loss. Finally, DCB treatment has shown noninferiority to DES in both STEMI and non-STEMI, suggesting it to be a safe and effective alternative supported by evidence across various acute coronary syndrome cases, affirming its clinical safety and angiographic efficacy in managing adverse cardiovascular-related outcomes. These results highlight the necessity for further research on DCB treatment, ideally through larger randomized trials using DES as control groups.

For patients with AMI, after identifying the infarct-related lesion, thrombus aspiration is conducted if the thrombus is observed, as determined by the operator (Figure 3). Although intravascular imaging can assist in the detection and confirmation of thrombus presence, as well as in assessing its successful removal, its role in thrombus burden quantification and evaluation during index procedures in AMI patients is relatively limited. Predilation with a plain balloon was mandatory, using a balloon-to-vessel ratio of 1.0. Stenting is deferred in all types of dissections (A to E) if TIMI flow grade 3 is achieved after predilatation.⁹⁶ Visual residual stenosis ≤30% without flow-limiting dissection is considered an adequate lesion preparation and followed by DCB treatment. If lesion preparation is inadequate or a flow-limiting dissection occurs before DCB application, switching to DES implantation without applying DCB is considered a provisional strategy rather than a bailout. The DCB is inflated to nominal pressure for at least 60 seconds, extending the DCB at least 2 mm beyond the initial pre-dilatation. Following the application of DCB, the final assessment is conducted at least 5 minutes after intracoronary vasodilator administration. In cases of substantial thrombus burden, a rescue strategy with glycoprotein IIb/IIIa receptor inhibitors is utilized.

Figure 3.

DCB Treatment Approach for Acute Myocardial Infarction

In acute myocardial infarction patients, the use of intravascular imaging can assist in the detection and confirmation of thrombus presence. Predilation with a 1.0 balloon-to-vessel ratio is required, followed by DCB treatment if the residual stenosis is ≤30% without flow-limiting dissection and the thrombus burden is low. If lesion preparation is inadequate or a high thrombus burden persists, DES implantation is employed as a provisional strategy. Abbreviations as in Figure 1.

Sirolimus-Coated Balloons Treatment

Paclitaxel continues to be widely used for balloon coating because of its high lipophilicity and potent antiproliferative effects.⁹⁷ However, recent studies have increasingly focused on alternative coatings and drug delivery technologies.^5,98,99 All currently available DES release sirolimus or its analogs, demonstrating superior outcomes compared with paclitaxel-eluting stents across various indications. Moreover, paclitaxel-eluting stents exhibit a higher stent thrombosis incidence than BMS and sirolimus-eluting stents.¹⁰⁰ Despite the superior safety and effectiveness of limus-eluting stents in coronary lesions compared with paclitaxel, sirolimus may encounter challenges when used in DCBs. When considering the mechanism of DCB treatment, these devices require rapid drug release and short transit times. However, sirolimus’s low lipophilicity and limited ability to penetrate and persist within the target vessel wall, particularly in the adventitia, hinder these requirements. In the first RCT comparing a novel sirolimus-coated balloon (SCB) to a widely used paclitaxel-coated balloon (PCB) for de novo coronary lesions, the SCB with a crystalline coating showed comparable angiographic outcomes.¹³ During the 6-month follow-up, in-segment late lumen loss measured 0.10 ± 0.32 mm and 0.01 ± 0.33 mm in the SCB and PCB groups, respectively. However, a higher late lumen enlargement incidence was noted among PCB-treated patients. In the TRANSFORM (Treatment of Small Coronary Vessels: MagicTouch Sirolimus Coated Balloon) I trial, patients with de novo single-vessel disease (≤2.75 mm) were randomly assigned to receive the MagicTouch SCB or the SeQuent Please Neo PCB.³⁷ This was primarily aimed at evaluating in-segment net lumen gain assessed by angiography during the 6-month follow-up. The SCB did not achieve noninferiority in terms of angiographic net gain at this time point compared with the PCB. This difference was primarily driven by a smaller late lumen loss and a higher incidence of late lumen enlargement with PCB. These findings indicate that paclitaxel demonstrates superior angiographic outcomes compared with sirolimus in DCB treatment, contrasting with its performance in stent-based drug delivery. However, larger-scaled studies with adequate sample sizes and sufficient statistical power are necessary to assess clinical outcomes and establish the efficacy of SCB compared to PCB in coronary lesions.

Future Direction of DCB Treatment

Ongoing randomized controlled trials

Recent data suggest that DCB treatment provides improved safety and efficacy across various clinical and angiographic scenarios (Tables 1 and 2). However, ongoing trials are being conducted to provide clear evidence regarding the DCB treatment of de novo large coronary vessels, bifurcation lesions, high-bleeding risk patients, and the use of sirolimus-coated balloons (Table 3).

Table 3.

List of Current Ongoing Randomized Controlled Trials of Drug-Coated Balloon Treatment in Coronary Artery Disease

NCT# Trial Name (Year)	Device (n)	Study Population	Primary Endpoint	Follow-up (mo)
NCT05846893 REVERSE (2023)	SeQuent Please NEO DCB (718) vs current-generation DES (718)	De novo large CAD (≥3.0 mm by visual estimation)	NACE: composite of all-cause death, nonfatal MI, TVR, or major bleeding	12
NCT06084000 STENTLESS (2023)	Bingo DCB (1,350) vs second-generation DES (1,350)	De novo large CAD (≥2.75 mm diameter)	MACE: composite of cardiac death, target-vessel MI, and TVR	12
NCT04664283 (2021)	DCB (127) by OCT-guided vs DES (127) by OCT-guided	De novo large CAD (vessel diameter 3.0-4.5 mm)	Late lumen loss by QCA	12
NCT04242134 DCB-BIF (2020)	PS-DCB (392) vs PS-NCB (392)	De novo true bifurcation lesions	MACE: composite of cardiac death, MI, and TLR	12
NCT05221931 DCB-HBR (2022)	DES (Ultimaster) (675) vs DCB (PCB) (675)	De novo coronary lesions in patients with high bleeding risk	TVF: composite of cardiovascular death, target-vessel MI, and TVR	24
NCT04814212 DEBATE (2022)	SeQuent® Please NEO DCB (273) vs DES (273)	De novo stable CAD or ACS patients at high risk of bleeding	MACE and major bleeding (MACE: composite of cardiac death, nonfatal MI, and TLR)	12
NCT04893291 TRANSFORM II (2021)	SCB (Magic Touch) DCB (910) vs EES DES (910)	De novo small and medium-sized coronary lesions (2-3 mm)	TLF and NACE (TLF: composite of cardiac death, all-cause death, MI, TLR, TVR, and bleeding; NACE: composite of all-cause death, MI, ischemic stroke, and major bleeding)	12
NCT04859985 SELUTION DeNovo (2021)	SCB (SELUTION SLR) DCB (1,663) vs DES (1,663)	De novo chronic coronary syndrome, unstable angina or NSTEMI	TVF (TVF: composite of cardiac death, target-vessel–related MI, and TVR)	12

ACS = acute coronary syndrome; CAD = coronary artery disease; EES = everolimus eluting stent; MI = myocardial infarction; NACE = net adverse clinical event; OCT = optical coherence tomography; PCB = paclitaxel coated balloon; QCA = quantitative coronary analysis; SCB = sirolimus coated balloon; other abbreviations as in Table 1.

For de novo large coronary vessels, the REVERSE trial (NCT05846893), aim to establish the noninferiority of DCB treatment compared with current-generation DES in patients with de novo lesions in large CAD (reference vessel diameter ≥3.0 mm by visual estimation). Similarly, the STENTLESS (STrategies of Scheduled Drug-coated Balloons [DCB] Versus Conventional DES for the interveNTional Therapy of de Novo Lesions in Large Coronary vESSels; NCT06084000) trial is investigating the safety and efficacy of scheduled DCB vs conventional DES strategies for treating de novo lesions in large coronary vessels (≥2.75 mm diameter). Another trial (NCT04664283) intends to determine if DCB is noninferior to DES in treating large vessel disease (3.0–4.5 mm vessel diameter), assessed via OCT.

The DCB-BIF (Drug-coating Balloon Angioplasties for True Coronary Bifurcation Lesions; NCT04242134) trial aims to determine if using DCB compared with conventional BA for the side-branch postprovisional stenting in true coronary de novo bifurcation lesions reduces the incidence of the composite endpoint of MACE at 12 months.¹⁰¹

The DCB-HBR (Drug-Coated Balloon Versus Drug-Eluting Stent for Treatment of De Novo Coronary Lesions in Patients With High Bleeding Risk; NCT05221931) aims to assess the clinical outcomes of DCB versus DES for treating de novo coronary lesions, guided by intravascular imaging optimization in high-bleeding risk patients. Additionally, the DEBATE (Drug-Coated Balloon in Anticoagulated and Bleeding Risk Patients Undergoing PCI; NCT04814212) trial is proposed to determine whether a DCB strategy with a shorter DAPT regimen is noninferior to a DES approach with longer DAPT in patients with stable CAD or acute coronary syndrome at high-bleeding risk, including those on anticoagulation therapy.

The TRANSFORM II (Sirolimus-coated Balloon Versus Drug-eluting Stent in Native Coronary Vessels; NCT04893291) trial aims to evaluate the use of DCB in treating small- and medium-sized de novo coronary lesions (2-3 mm) by comparing MagicTouch DCB with everolimus-eluting stents, focusing on TLF at 12 months of follow-up.¹⁰² The SELUTION DeNovo trial (NCT04859985) is designed to demonstrate noninferiority at 1 year for TVF of a treatment strategy with SCB and provisional DES vs DES in de novo coronary lesions.¹⁰³

Metal-free PCI

Although DES technologies have significantly improved the safety and efficacy of PCI in treating obstructive CAD, the permanent presence of a metallic stent in the coronary artery can result in vascular inflammation, hypersensitivity reactions, accelerated neoatherosclerosis, stent thrombosis, and compromised late luminal enlargement and vasomotor function.¹⁰⁴ Therefore, to overcome these issues with DES, bioresorbable scaffolds were developed to support vessel walls for a certain period and then gradually disappear as the vessels heal. However, it was withdrawn from the market caused by its inferior performance compared to contemporary DES in treating CAD.^105,106 The failure of bioresorbable scaffolds has further promoted DCBs’ introduction and advancement with the “leave nothing behind” concept, highlighting their growing significance. Nevertheless, because the basic concept of bioresorbable scaffolds is sound, their development should continue. Therefore, considering previous failures, we anticipate that the development of new-generation bioresorbable scaffolds, alongside DCB innovations, could pave the way for a new era of metal-free PCI, representing a significant leap in the treatment of CAD. Including this perspective in the context of DCB therapy highlights critical areas for future research and addresses unanswered questions, fostering innovation and expanding the therapeutic landscape.

Conclusions

Although current recommendations for DCB treatment in CAD are limited to ISR lesions and de novo small vessel disease, it remains an appealing therapeutic option and could play a significant role in managing de novo coronary lesions across various disease subsets. DCB provides an additional tool in PCI that can enhance patient outcomes by addressing lesions previously challenging or less responsive to DES implantation. For more complex lesions, including de novo large vessel disease, bifurcation disease, and complex high-risk PCI, further use of intravascular imaging or functional measurements can provide valuable insights. Advancements in DCB technology, coupled with improvements in imaging techniques, physiologic guidance, and adjunctive pharmacotherapy, will also be essential to improving clinical outcomes in CAD management. DCB treatment is expected to play a pivotal role, particularly in the Asia-Pacific region, where patients usually present with small vessel disease or multiple diffuse lesions leading to increased adverse clinical events with DES implantation. Therefore, prioritizing the proper implementation of DCB procedures is essential to enhance the likelihood of successful outcomes. Finally, newer generation bioresorbable scaffold development and adoption in the future may enable metal-free PCI alongside DCB, potentially leading to changes in the field of PCI and improvements in outcomes for patients with CAD.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.