Despite significant advancements in stent technology, numerous challenges persist in modern coronary intervention. Current literature underscores the effectiveness of drug-eluting stents (DES) in significantly lowering restenosis rates when compared to bare metal stents (BMS), from approximately 30% with BMS to around 5–10% with DES.1 Despite considerable advancements in DES technology, in-stent restenosis (ISR) and the requirement for target lesion revascularisation continue to occur at an annual rate of 1–2% with current DES platforms.2 Given the implantation of millions of DES worldwide each year, ISR is a pathological condition of significant public health concern. Notably, percutaneous coronary intervention (PCI) performed following ISR has accounted for about 10% of all PCI procedures in the US over the past decade and is associated with a higher incidence of major adverse cardiac events (MACE) compared to PCI for de novo lesions.3 Moreover, challenges remain in managing lesions in small-calibre vessels and reducing the need for prolonged antiplatelet therapy in patients at high risk of bleeding.
The advent of drug-eluting balloons (DEB) represents a paradigm shift towards intervention without implantation. This strategy delivers antiproliferative agents directly to the lesion site, leaving no permanent metallic or polymeric residue. DEB technology employs drugs like paclitaxel and sirolimus to inhibit neointimal proliferation and has demonstrated favourable outcomes in both randomised trials and real-world registries.4–6
While global data on DEB in ISR efficacy is robust, there remains a gap in systematic evaluation within acute coronary syndrome (ACS) patients and in de novo lesions in the Indian population. Given the unique clinical profile of Indian patients, characterised by earlier onset and more extensive coronary artery disease, exploring the efficacy of DEB in this cohort is essential. This study seeks to fill a critical gap in the literature by providing comprehensive insights into the short-term efficacy of DEB in treating ACS and de novo lesions in Indian patients, a population currently underrepresented in the literature.
Materials and Methods
This single-centre retrospective study was conducted at a tertiary care cardiology centre in central India. Data collection commenced following approval from the institutional ethics committee. We reviewed medical records of patients treated with DEBs from 1 January 2015 to 30 June 2024. Demographic data, comorbidities, laboratory parameters, 2D echocardiography and coronary angiography findings were recorded and analysed using Microsoft Excel. Coronary angiography and 2D echocardiography were performed by trained cardiologists in accordance with hospital protocols.
Angiographic measurements were visually estimated by two cardiologists. A diameter stenosis of 50% in the coronary segment was considered significant. In-stent restenosis was classified as either focal (≤10 mm) or diffuse (>10 mm).7 Initial treatment involved conventional angioplasty with a balloon-sized 1:1 relative to the artery, followed by DEB angioplasty using sirolimus-eluting (Magic Touch [Concept Medical Inc, US]/MOZEC™ SEB [Meril Life Sciences, India]) or paclitaxel-eluting (PREVAIL™ [Medtronic, US]/Essential Pro [iVascular, Spain]) balloons, with inflation lasting at least 1 minute. Patients were maintained on dual antiplatelet therapy for at least 1 year, consisting of aspirin combined with either clopidogrel or ticagrelor, at the cardiologist’s discretion. The primary outcome was a 5-point MACE, a composite measure including all-cause mortality, myocardial infarction, stroke, repeat revascularisation and hospitalisation due to heart failure, assessed through clinical evaluations during outpatient visits or telephonic follow-up.
Results
Table 1 presents the baseline characteristics of the study cohort. In our analysis, 70 drug-eluting balloons were deployed across 65 patients. The mean age of the cohort was 60.1 ± 12.5 years, with an approximately equal proportion of patients aged above and below 60 years. The male population constituted 89.2% of the sample. Hypertension was observed in 63.1% of the patients, while diabetes was present in 58.5%. The mean ejection fraction was recorded at 51.0 ± 10.4%. Figure 1 illustrates the patients’ clinical presentation at admission. A total of 46 patients (70.8%) presented with ACS, whereas 19 patients (29.2%) were classified as non-ACS on presentation. Among patients with ACS, the subtypes were unstable angina in 47.8% of cases, non-ST-elevation MI (NSTEMI) in 32.6% and ST-elevation myocardial infarction (STEMI) in 19.6%.
Supplementary Table 1 presents the vessels treated with DEBs. The left anterior descending artery (LAD) was the most frequently treated vessel (41.5%). Other commonly treated vessels included the diagonal artery (18.5%), right coronary artery (11.3%), left circumflex artery (11.3%) and obtuse marginal artery (11.3%).
Table 2 summarises the angiographic characteristics of the study cohort. DEB angioplasty was used for in-stent restenosis in 32.2% of cases and for stent thrombosis in 1.5% of cases, while the majority of DEB angioplasty (66.2%) were performed for de novo lesions. Within the in-stent restenosis group treated with DEB, the distribution of diffuse versus discrete lesions was approximately equal. The DEB procedure targeted the culprit vessel in 86.2% of patients. Coronary imaging was performed in 15.4% of patients. The mean SYNTAX score was 10.7 ± 4.7, and stenting post-DEB was required in 1.5% of patients. Figure 2 demonstrates DEB angioplasty in the LAD of a patient presenting with ACS.
Table 3 outlines the characteristics of the balloons used. A total of 70 balloons were used, with sizes ranging from 2 × 10 mm to 3.5 × 40 mm. The mean diameter was 2.7 mm and the mean length was 22.46 mm. For de novo lesions, the mean balloon diameter and length were 2.54 mm and 22.59 mm, respectively. For ISR, mean balloon diameter and length were 3.05 mm and 22.17 mm, respectively. Sirolimus-eluting DEBs were used in 81.5% of cases, while paclitaxel-eluting DEBs were used in 18.5%. Among the sirolimus-eluting DEBs (n=57), MagicTouch and MOZECTM SEB were used in 42 (73.7%) and 15 (26.3%) cases, respectively. For paclitaxel-eluting DEBs (n=13), PREVAILTM and Essential Pro were used in 10 (76.9%) and three cases (23.1%), respectively.
Our study involved short-term follow-up with a median duration of 257 days. Supplementary Figure 1 illustrates patient outcomes based on the 5-point MACE criteria. Among the 65 patients, three patients (4.6%) required re-hospitalisation for unstable angina, necessitating reintervention in each case. Of these, one patient had undergone DEB angioplasty for a de novo lesion and two patients had undergone DEB angioplasty for ISR.
The first case of DEB failure involved a de novo lesion in a diffusely diseased, small-calibre and heavily calcified LAD, where adequate vessel preparation was challenging. The patient was managed conservatively with escalation of antianginal therapy and remains asymptomatic on optimal medical management. The second case, involving ISR, was addressed with intravascular ultrasound-guided DEB angioplasty using a larger DEB than previously used to ensure adequate luminal gain. In the other case of DEB failure following ISR, a DES was implanted to achieve optimal lesion coverage and restore vessel patency.
There were no reported cases of non-fatal MI, deaths, stroke or hospitalisation for heart failure during the follow-up period.
Discussion
Our single-centre study included 65 patients with diverse coronary anatomy, focusing on the real-world application of DEBs in an Indian cohort. The cohort in our study had a high incidence of ACS (70.8%), with unstable angina being the most common presentation (47.8%) followed by NSTEMI and STEMI. Notably, a significant proportion of patients (66%) were treated for de novo lesions, the majority of whom presented with ACS (70%). Our study uniquely includes a high number of patients undergoing DEB treatment for de novo lesions in the context of ACS. These data are particularly important as our literature review indicates a lack of such data in Indian populations.
Comparative analysis with other studies in India reveals consistent findings. Gunasekaran et al. reported their experience with DEBs, emphasising their efficacy and safety in treating various coronary lesions including ISR and de novo lesions.8 Similarly, Swamy et al. documented favourable outcomes with DEBs in a predominantly Indian population, underscoring a low incidence of adverse events and high procedural success in ISR lesions.9 Our study contributes additional data to this growing body of evidence, highlighting the effectiveness and safety of DEBs in a real-world Indian cohort, especially for de novo lesions in ACS patients.
In our experience, the use of DEBs for ISR among 21 patients (32% of our total patient cohort) resulted in three patients (15% of the ISR cohort) requiring repeat target lesion revascularisation. This finding aligns with the ISAR-DESIRE 3 trial, which concluded that 10 years post-PCI for drug-eluting stent ISR, the clinical endpoints between paclitaxel-coated balloons and paclitaxel-eluting stents were not significantly different.10 This suggests that DEBs are a viable alternative to paclitaxel-eluting stents in the long-term management of ISR.
The use of DEBs is particularly advantageous for patients with multiple previous stent layers, patients with significant side branches emerging from the stent with ISR and patients requiring a shorter dual-antiplatelet regimen. These characteristics make DEBs a suitable choice for complex coronary anatomies, where traditional stenting approaches may carry higher risks or present technical challenges. Consequently, the treatment of ISR with DEBs has been incorporated into the current European guidelines on myocardial revascularisation, earning a class 1a recommendation.11 This endorsement underscores the growing recognition of DEBs as an effective and safe option for ISR treatment, reflecting their clinical utility and robust outcomes in diverse patient populations.
Moreover, DEBs are an excellent tool for managing bifurcation lesions, reducing procedural complexity and metal load. This advantage is supported by the PEPCAD-BIF study, which concluded that DEBs represent a sound and effective strategy in bifurcation lesions.12 Bifurcation lesions are known for their complexity and higher risk of complications. DEBs simplify the procedure and potentially reduce the need for additional stenting. In our study, we used DEBs in five patients with bifurcation lesions and observed favourable outcomes, further supporting their efficacy in such cases. The positive results in our cohort align with the findings of the PEPCAD-BIF study, reinforcing the value of DEBs in managing bifurcation lesions.
As discussed, our cohort had a high incidence of ACS (70%) with robust short-term follow-up. Limited data exist for ACS scenarios, but two recent trials, PEPCAD NSTEMI and REVELATION, support the use of drug-coated balloons (DCBs) in such contexts. The PEPCAD NSTEMI trial found that DCB treatment of de novo lesions in NSTEMI patients with identifiable culprit lesions and no large thrombus was non-inferior to stenting with BMS or DES.13 Similarly, the REVELATION trial concluded that DCBs were comparable to DES in selected STEMI patients with non-severely calcified culprit lesions and residual stenosis <50% after predilatation, demonstrating excellent clinical outcomes. This result mirrors our real-world experience and reinforces their utility in ACS treatment.14
Most of our DEB use was in small vessels and de novo lesions, with an average balloon diameter of 2.7 mm. We did not observe any flow-limiting dissections or acute closures post-DEB use. Following DEB treatment, residual stenosis was less than 30% in all patients. In one case, the dissection in the left main artery was non-flow-limiting but was stented due to its critical location and safety concerns. There were three MACE (4.6%) in the small vessel group with in-stent restenosis requiring revascularisation, but no deaths. Our positive real-world experience in small vessels is supported by the BASKET-SMALL 2 trial, a multicentre, open-label, randomised non-inferiority trial, which found that DEB therapy was non-inferior to second-generation DES for MACE up to 12 months.15
Furthermore, the Third Report of the International DCB Consensus Group states that a DCB-only approach for de novo lesions in coronary small-vessel disease is now considered a valid treatment alternative to DES, provided that current recommendations for optimal balloon angioplasty and DCB delivery are followed.16 This endorsement from an international consensus group adds significant weight to the growing body of evidence supporting the use of DEBs in various clinical settings. The consensus report emphasises the importance of adhering to optimal procedural techniques to maximise the benefits of DEBs and minimise potential complications.
In our cohort, the consistent success of DEBs in small vessels and de novo lesions highlights their versatility and reliability as a therapeutic option. The absence of flow-limiting dissections or acute closures post-DEB use suggests that DEBs can be safely employed in complex coronary anatomies, reducing the need for additional stenting and its associated risks. Our experience, in conjunction with the findings from the PEPCAD NSTEMI, REVELATION and BASKET-SMALL 2 trials, supports the broader adoption of DEBs in clinical practice, particularly in cases where traditional stenting may pose higher risks or be less effective.
While our study’s findings are encouraging, it is also important to address its limitations. Firstly, as a retrospective study, it is inherently subject to biases and limitations in data collection, which may affect the reliability of our findings. Secondly, coronary angiograms were not performed as part of follow-up; instead, clinical examinations or telephonic follow-ups were used, which may not fully capture the extent of coronary events or provide a comprehensive assessment of the patients’ conditions. Thirdly, the follow-up period was relatively short, with a median duration of 257 days, limiting our ability to assess long-term outcomes and the durability of the treatment effects observed. Additionally, our cohort primarily consisted of patients with lower SYNTAX scores and selectively included ACS patients with low or no thrombus burden. This selective inclusion likely contributed to the lower incidence of MACE observed in our study, potentially affecting the generalisability of our findings to a broader population with more complex or severe coronary artery disease. These limitations should be considered when interpreting the results and applying them to clinical practice. Additional limitations of this study are its relatively small sample size, collected over a span of 9 years, during which significant advancements in pharmacological therapies and vessel preparation techniques occurred. Furthermore, the study may lack sufficient statistical power to draw definitive conclusions regarding safety and efficacy of DEBs across a broad spectrum of all-comer lesions.
Conclusion
In conclusion, the incorporation of DEBs into therapeutic protocols for ACS, small vessel disease and de novo lesions signifies a profound advancement in interventional cardiology. DEBs, with their ability to deliver outcomes comparable to DES while simultaneously reducing metal burden and procedural complexity, have emerged as an invaluable tool for clinicians.
Clinical Perspective
- In our real-world experience, DEBs demonstrated excellent short-term efficacy and safety in managing ACS and diverse coronary anatomies including ISR, de novo lesions, bifurcations and small calibre vessels.
- Meticulous case selection is imperative, favouring patients with low SYNTAX scores and minimal thrombus burden.
- DEB therapy could be considered a promising alternative to traditional stent-based interventions in selected patients.