REC-CAGEFREE I - Drug-coated balloon angioplasty with rescue stenting versus intended stenting for the treatment of de novo coronary artery lesions
Reported from ESC Congress 2024
Mirvat Alasnag provides her take on REC-CAGEFREE I, a multicenter, non-inferiority trial presented at the ESC Congress 2024 in London.
Background
There has been growing enthusiasm for drug-coated balloon (DCB) technology in recent years. Evidence has mounted from multiple trials such as the BASKET-SMALL 2, PICCOLETO II, and AGENT IDE trials. (1-3) In May 2023 the European Society of Cardiology issued a statement on DCB encouraging the community to generate more evidence. (4) As a technology it is available in Europe, Asia Pacific, and Latin America where it is commonly applied for in-stent restenosis, side branches and small-vessel coronary disease. Studies such as Hybrid DEB are evaluating DCBs in chronic total occlusions; PICOLETTO III is designed for complex lesions and other studies have explored its role in individuals who are at high bleeding risk.
REC-CAGEFREE I (Drug-coated balloon angioplasty with rescue stenting versus intended stenting for the treatment of patients with de novo coronary artery lesions) is designed to test for de novo, non-complex lesions. (5)
Methods
REC-CAGEFREE I is an open-label, randomised, non-inferiority trial that was conducted in 43 sites in China. Patients aged 18 years or older with de novo, non-complex coronary artery disease and an indication for percutaneous coronary intervention (PCI). A non-complex PCI was defined as one treating one or two target lesions or vessels, one or two planned DES or DCB devices, planned total DES or DCB length of 60 mm or shorter. Both acute and chronic coronary syndrome cases were enrolled with de novo coronary lesions of native vessels regardless of treated vessel diameter. Exclusion criteria included cardiogenic shock, in-stent restenosis, Left Main stenosis, complex bifurcations and chronic total occlusions. Patients were randomly assigned 1:1 to paclitaxel-coated balloon angioplasty with the option of rescue stenting due to an unsatisfactory result (DCB arm) or pre-planned deployment of second-generation thin-strut sirolimus-eluting stents (DES arm). Successful angioplasty was defined as visual residual stenosis < 30% with TIMI 3 flow and no type D, E, F dissections.
The primary outcome was the device-oriented composite endpoint of cardiovascular death, target vessel myocardial infarction (TV-MI), and clinically and physiologically indicated target lesion revascularisation (TLR) at 24 months using an intention-to-treat (ITT) analysis. Device safety was also evaluated.
Results
A total of 2272 patients were enrolled with 50% in each arm. The median age was 62 years and 69·3% were men. In the DCB arm, 9·4% of the 1133 patients required bailout stenting due to TIMI 2 or less flow or Type D-F dissection or visual residual stenosis > 30%. Median follow-up was 734 days. At 24 months, the composite primary endpoint occurred in 6·4% of the DCB arm and 3·4% of the DES arm (NNT: 33). The predefined non-inferiority mark was not met. As for the individual components of the composite, cardiac death was reported in 1.2% in DES vs 3% in DCB (P=.05), TV MI: 1.6% DES vs 1.9% DCB which was not significantly different, and clinically and physiologically driven TLR: 1.2% DES vs 3.1% DCB (P=.002).
In terms of safety, no acute vessel closures occurred in the DCB arm and only one (0·1%) in the DES arm. Periprocedural myocardial infarction (MI) occurred in 0·9% of the DCB arm and 0.8% of the DES arm. It is interesting to review the results stratified by vessel size with small (defined as < 3mm) vs non-small (> 3mm); the differences between the two strategies were more evident in larger vessel sizes whereby the small vessel the primary endpoint in the small vessels was DES 4.4% vs 5.1% DCB and in the non-small vessel the primary endpoint occurred in DES 2.5% vs 7.5% DCB.
Conclusion & discussion
The study was powered for the defined clinical endpoints investigating the use of DCB in patients with de novo disease. A strategy of DCB with rescue stenting failed to reach non-inferiority compared to intended strategy of DES at 2 years. The investigators conclude that DES implantation should remain the preferred treatment strategy for such patients. Although the results may curb some enthusiasm for DCB use in de novo lesions, DCB remains an attractive option for small vessels where the difference was insignificant compared with larger vessels in this and other studies.
Furthermore, not all DCB technologies are the same. Not only are the agents used differently, but the amorphous or crystalline construct may play a role. A direct correlation between late lumen loss and dissection volume with the different designs has been postulated. A more rudimentary theory of barotrauma triggering events is plausible. Intracoronary imaging may permit us to weed out lesion and vessel-level triggers of adverse events. It is important to note that most of the trials are enrolled in small numbers and the event rates were small making it difficult to identify drivers. As such, the ESC’s call for more evidence remains still valid.
References:
- Fahrni G, Scheller B, Coslovsky M, Gilgen N, Farah A, Ohlow MA, Mangner N, Weilenmann D, Wöhrle J, Cuculi F, Leibundgut G, Möbius-Winkler S, Zweiker R, Twerenbold R, Kaiser C, Jeger R; BASKET-SMALL 2 Investigators. Drug-coated balloon versus drug-eluting stent in small coronary artery lesions: angiographic analysis from the BASKET-SMALL 2 trial. Clin Res Cardiol. 2020 Sep;109(9):1114-1124.
- Ahmad WAW, Nuruddin AA, Abdul Kader MASK, Ong TK, Liew HB, Ali RM, Mahmood Zuhdi AS, Ismail MD, Yusof AKM, Schwenke C, Kutschera M, Scheller B. Treatment of Coronary De Novo Lesions by a Sirolimus- or Paclitaxel-Coated Balloon. JACC Cardiovasc Interv. 2022 Apr 11;15(7):770-779.
- Yeh RW, Shlofmitz R, Moses J, Bachinsky W, Dohad S, Rudick S, Stoler R, Jefferson BK, Nicholson W, Altman J, Bateman C, Krishnaswamy A, Grantham JA, Zidar FJ, Marso SP, Tremmel JA, Grines C, Ahmed MI, Latib A, Tehrani B, Abbott JD, Batchelor W, Underwood P, Allocco DJ, Kirtane AJ; AGENT IDE Investigators. Paclitaxel-Coated Balloon vs Uncoated Balloon for Coronary In-Stent Restenosis: The AGENT IDE Randomized Clinical Trial. JAMA. 2024 Mar 26;331(12):1015-1024.
- https://www.escardio.org/The-ESC/Press-Office/Press-releases/interventions-with-drug-coated-balloons-a-pcr-statement
- Gao C, He X, Ouyang F, Zhang Z, Shen G, Wu M, Yang P, Ma L, Yang F, Ji Z, Wang H, Wu Y, Fang Z, Jiang H, Wen S, Liu Y, Li F, Zhou J, Zhu B, Liu Y, Zhang R, Zhang T, Wang P, Liu J, Jiang Z, Xia J, van Geuns RJ, Capodanno D, Garg S, Onuma Y, Wang D, Serruys PW, Tao L; REC-CAGEFREE I Investigators. Drug-coated balloon angioplasty with rescue stenting versus intended stenting for the treatment of patients with de novo coronary artery lesions (REC-CAGEFREE I): an open-label, randomised, non-inferiority trial. Lancet. 2024 Aug 30:S0140-6736(24)01594-0.
Related publications
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