Refining DAPT strategies after drug coated balloon angioplasty

The evolution of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) has been shaped by the continuous challenge of balancing ischaemic protection with bleeding risk. While prolonged DAPT confers thrombotic risk reduction, it invariably increases bleeding complications, which are themselves associated with adverse prognostic implications.1 This dilemma has prompted the exploration of de-escalation strategies—gradual tapering of antiplatelet intensity or duration—as a means of optimising patient outcomes. Currently, the concept of DAPT de-escalation refers to the strategy of discontinuing aspirin after a short period of dual antiplatelet therapy after PCI, leaving patients on monotherapy with a potent P2Y12 inhibitor—typically ticagrelor, as supported by available evidence.234 The rationale behind this approach is to maximise ischaemic protection during the initial months after PCI, when the thrombotic risk is highest, while simultaneously mitigating the bleeding risk, which remains relatively constant and is directly associated with DAPT duration.5 In a previous meta-analysis from our group, DAPT de-escalation was indeed associated with a significant reduction of bleeding events in patients with acute coronary syndrome compared with five alternative standard DAPT strategies, while not increasing the risk of ischaemic events, even rare ones, such as stent thrombosis.6

Cardiovascular research has struggled over the past decade to develop accurate scores to precisely estimate the trade-off between ischaemic and bleeding risks, even by means of artificial intelligence.789 However, most existing scores prioritise clinical and demographic factors while minimally incorporating procedural data. Notably, patients undergoing drug coated balloon (DCB) treatment—where an angioplasty balloon coated with an antiproliferative drug (eg, paclitaxel or sirolimus) is inflated to deliver drug treatment directly to the arterial wall without leaving a permanent metal scaffold—are not sufficiently represented in the datasets from which these risk models were derived, leaving a substantial gap in evidence based decision making for this subgroup.

Concurrently, the paradigm of PCI has been reshaped by the growing adoption of DCB, an appealing alternative to conventional stenting, particularly for challenging lesion subsets such as in-stent restenosis (re-narrowing within a previously placed stent), small vessel disease (typically vessels <2.5 mm in diameter, that are associated with increased thrombotic risk), and bifurcations (branch points in the coronary arteries). In these scenarios, conventional stenting might necessitate multiple overlapping stents or complex two-stent techniques (eg, double-kissing crush, culotte stenting), which not only increase procedural complexity and metal burden but also correlate with poorer PCI outcomes. By delivering antiproliferative drug treatment without leaving a permanent scaffold, DCB might help avoid or reduce the need for these complex stenting strategies.10 The absence of a permanent metallic scaffold, polymer, or long term antiproliferative drug exposure theoretically allows for a more lenient DAPT regimen.11 However, this concept remains speculative. DCB angioplasty avoids the long term drawbacks of stents—such as chronic inflammation around the metal struts, neoatherosclerosis, stent thrombosis, and the potential for future re-intervention challenges. However, it leaves the atherosclerotic and inflamed endothelium vulnerable to procedural trauma, residual dissections, and drug induced endothelial dysfunction, thereby necessitating a tailored antithrombotic approach. Yet, the optimal DAPT strategy after DCB remains an unresolved clinical question.

A linked study (doi:10.1136/bmj-2024-082945), the REC-CAGEFREE II trial, provides useful evidence addressing this knowledge gap.12 This multicentre, open label, assessor blind, non-inferiority trial enrolled 1948 patients across 14 hospitals in China with acute coronary syndrome who underwent PCI with paclitaxel coated balloons. Patients were randomised to a stepwise DAPT de-escalation regimen (aspirin plus ticagrelor for one month, followed by ticagrelor monotherapy for five months, then aspirin monotherapy for six months) or standard DAPT for 12 months with aspirin and ticagrelor. The primary endpoint, a composite of all cause death, stroke, myocardial infarction, revascularisation, and major bleeding, occurred at comparable rates in both groups (8.9% v 8.6%), establishing non-inferiority. Moreover, stepwise de-escalation conferred a significant reduction in major bleeding.

The study had several strengths. Firstly, its exclusive focus on patients with acute coronary syndrome—who inherently have a heightened thrombotic risk—provides a stringent test of de-escalation safety.13 Secondly, the trial reflects contemporary real world indications for DCB treatment, encompassing small vessels, in-stent restenosis, and bifurcations, which are complex anatomical settings that theoretically require longer DAPT.14 Additionally, the study leveraged a sophisticated array of secondary endpoint analyses, including hierarchical testing and sensitivity analyses. Notably, the findings were consistent across several lesion settings (ie, de novo lesions v in-stent restenosis) and in subgroups at high ischaemic risk. Nevertheless, the study’s limitations warrant careful consideration. The generalisability of findings might be constrained by the under-representation of people with ST elevation myocardial infarction, because DCB is seldom used in thrombotic lesions. Furthermore, the benefits of de-escalation seem to be contingent on potent P2Y12 inhibition, as shown by the higher incidence of the patient-oriented composite outcome in the intention-to-treat cohort than in the per protocol cohort. The intention-to-treat cohort did include a broader group of patients who were treated with clopidogrel instead of ticagrelor owing to side effects. The study exclusively investigated paclitaxel coated balloons, precluding extrapolation to sirolimus based technologies. Furthermore, the cohort was predominantly East Asian, raising questions regarding applicability to other ethnic groups with varying bleeding and thrombotic propensities. Another important consideration is that while reducing bleeding risk is crucial, DAPT confers systemic ischaemic protection beyond the procedural setting. The role of DAPT in mitigating non-target vessel events and overall thrombotic burden cannot be overlooked,15 so, while de-escalation strategies are attractive, they should be selectively applied to patients at high bleeding risk rather than universally implemented.

Despite these caveats, REC-CAGEFREE II marks a step forward, translating the theoretical benefits of DCB treatment into actionable clinical practice. By demonstrating the feasibility of structured DAPT de-escalation in patients with acute coronary syndrome undergoing DCB angioplasty, the study provides a compelling rationale for refining current antiplatelet strategies. Future research should validate these findings in broader populations and assess alternative de-escalation algorithms, particularly in the context of emerging sirolimus-coated technologies.

Engaging with the perspectives of patients is paramount in shaping treatment paradigms. After reviewing the study findings summarised in this article, the patients and volunteers’ association of Amici del Cuore (Friends of the Heart) in Turin, Italy, emphasised the importance of striking a delicate equilibrium—reducing bleeding risk while preserving ischaemic protection. The group consistently expressed a preference for regimens that mitigate medication burden and adverse effects, without compromising safety. Their insights underscore the real world relevance of individualised DAPT strategies, particularly for those who prioritise bleeding avoidance over theoretical ischaemic risk.

As the field of PCI continues to advance, REC-CAGEFREE II is a poignant reminder that, in some instances, letting go of intensive therapy does not translate into a compromise in care. Rather, it represents a step towards a more refined, risk adjusted approach—where less may indeed be more.