1.1 DCBs for De Novo Coronary Lesions: Which Lesions and Are We There Yet?

These proceedings summarize the educational activity of the 17th Biennial Meeting of the International Andreas Gruentzig Society held January 30 to February 2, 2024 in Chiang Rai, Thailand.

Faculty Disclosures     Vendor Acknowledgments

2024 IAGS Summary Document

Statement of the problem or issue

Drug-coated balloons (DCBs) combine an angioplasty balloon with an anti-proliferative drug. They have several potential advantages over metallic drug-eluting stents and bioresorbable scaffolds in maintaining coronary distensibility, vasomotor function, and preventing chronic inflammation which can lead to neoathrosclerosis. In the United States (US) there are no FDA-approved DCBs currently available, even though the first DCB was CE-marked in Europe in 2007, and they have been under investigation outside the US for more than a decade. There are currently 14 companies that manufacture paclitaxel-coated balloons, and several other DCBs using sirolimus or biolimus are under development. There has been a steady increase in DCB use outside of the US. In Japan, for example, they were first approved in 2014, and that year they were used in 6% of PCI procedures; last year it was 21% of interventions. So, over fifty thousand interventions were performed with DCBs.

Paclitaxel has many characteristics that make it well suited for DCB application. It is rapidly absorbed, taken up in the subintimal space, and then distributes to the adventitia. Drug persistence and durability in these tissues over long periods of time has been demonstrated. Its safety, although debated for a few years, has now been accepted, and the dosing is well worked out. Sirolimus, on the other hand, has presented a more difficult challenge because of certain biological and technical limitations. However, with new crystalline formulations, micro-reservoirs, and other new technologies, there are experimental data for sirolimus-coated balloons showing very effective drug concentrations in the vessel wall for up to 90 days. We will likely see several very effective DCBs available in the near future. Several of their purported advantages have been borne out. The most important one is that serial angiographic and OCT studies have shown that 40% to 50% of vessels treated with a DCBs will demonstrate positive remodeling on follow-up imaging, not to the degree of being aneurysmal, but allowing for vessel growth, which is not allowed with metal scaffolds.

Gaps in current knowledge

There is limited experience with non-paclitaxel anti-proliferative formulations. Furthermore, clinical data are limited for most lesion and patient subsets of interest, for example, in long lesions, bifurcations, and in patients with acute coronary syndromes (ACS). The largest amount of available data relates to in-stent restenosis and small vessels.

The optimal delivery method is not yet understood. Sometimes DCBs are bulkier devices than regular balloons, and the anti-proliferative drugs only reside on the balloon surface for a certain amount of time. Efficient catheter delivery to the target vessel is very important. In a retrospective study which examined DCBs delivered through a Guideliner versus regular direct delivery, there was a lower rate of TLR in the Guideliner-delivery group, despite the target lesions being a much more anatomically complex group. This raises important questions: If you can't get the DCB rapidly to the target lesion, how effective will it really be?

Another gap area is methodology and criteria to assess immediate procedural outcome. Outside the US, consensus groups have proposed residual stenosis < 30%, presence of TIMI-III flow, FFR > 0.8, and absence of deep medial dissections or type C or greater dissections.

Device cost and reimbursement will be major issues, especially in the United States. Now that drug-eluting stents are typically under $300, how will DCBs compete with these low prices? If DCBs are reimbursed at balloon angioplasty rates, it will be difficult to achieve substantial uptake among interventionalists.

Possible solutions and future directions

Physician training is paramount. The DCB industry has taken on much of the responsibility for controlled release of new devices and insuring that physicians are trained to use their products. Post-marketing surveillance registries and other clinical registries will be key to understanding the adoption of DCBs and tracking outcomes. In the United States, as seen with other new devices, randomized trials examining patient and lesion subsets will help. Eventually, guidelines and consensus statements will be developed which will assist clinicians with: (1) selecting appropriate patients and lesion types for DCB treatment; (2) assessing techniques for optimal vessel and lesion preparation; (3) providing algorithms that outline when a DCB-only strategy is acceptable and scenarios in which a bail-out stent approach should be considered. Techniques for rapid and efficient device delivery will also have to be examined. Finally, artificial intelligence could potentially be used to review millions of procedures and look at characteristics that would be favorable for DCB intervention. For example, are intermediate lesions or vulnerable plaques appropriate candidates for DCB treatment?

Reference

1. Jeger RV, Eccleshall S, Wan Ahmad WA, et al. Drug-coated balloons for coronary artery disease: Third Report of the International DCB Consensus Group. JACC Cardiovasc Interv. 2020;13(12):1391-1402.