REC-CAGEFREE I Trial Compares Paclitaxel DCB and Sirolimus DES to Treat De Novo Noncomplex CAD

September 9, 2024—In the first randomized trial to compare clinical outcomes in previously untreated patients with noncomplex disease undergoing percutaneous coronary intervention (PCI), novel drug-coated balloons (DCB) were not superior to standard treatment with second-generation drug-eluting stents (DES), announced the European Society of Cardiology (ESC).

In its recent press release, the society advised that the surprising findings from the REC-CAGEFREE I randomized trial were presented in a Hot Line Session at the ESC Congress 2024 held August 30 to September 2 in London, United Kingdom. Ling Tao, MD, from Xijing Hospital in Xi’an, China, is senior author of the trial findings.

As noted by ESC, the background of REC-CAGEFREE I is that previous studies have shown the strategy of DCB angioplasty with the option of stenting in case of an unsatisfactory result to be just as effective as DES for previously untreated small vessel coronary artery disease (CAD) (diameter ≤ 3.0 mm). However, the long-term efficacy and safety of this strategy in previously untreated coronary lesions, regardless of coronary artery diameter, remains uncertain.

According to ESC, to investigate this issue, the REC-CAGEFREE I randomized, noninferiority trial enrolled patients requiring PCI who had previously untreated, noncomplex CAD (irrespective of target vessel diameter) from 43 sites across China.

Between February 2021 and May 2022, a total of 2,272 patients (age, ≥ 18 years) who had achieved a successful target vessel predilation were randomly assigned in a 1:1 ratio to receive one of the following:

• Treatment with paclitaxel DCB angioplasty with the option of rescue stenting because of an unsatisfactory result (DCB; 1,133 patients), or
• Deployment of a second-generation, thin strut, sirolimus DES (1,139 patients)

The patients’ average age was 61 years; 69% were men; 27% had diabetes; and 6% were insulin dependent. In total, approximately 9% (106/1,133) of patients had to undergo rescue DES after unsatisfactory DCB angioplasty.

As summarized in the ESC press release, the primary endpoint was the 2-year combined rate of cardiac death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization (device-oriented composite endpoint [DoCE]). The primary endpoint was 6.4% (72 patients) for DCB and 3.4% (38 patients) for DES, with an absolute risk difference of 3.04% (which was above the prespecified 2.68% threshold for noninferiority). The difference was mainly because of higher rates of clinically and physiologically indicated target lesion revascularization with DCBs (3.1% vs 1.2%; difference, 1.9%).

However, as noted in the ESC press release, a subgroup analysis found that there was a notable heterogeneity in the treatment effect across vessel diameters, which requires further confirmation in adequately designed trials. Although DES was the more favorable option in the non-small vessel disease subpopulation (device diameter > 3 mm), in the small vessel disease subpopulation (≤ 3 mm) with more than 1,000 patients, the results were in line with previous studies showing that DCB and DES had similar rates of DoCE through the 2-year follow-up (P-value for the interaction between treatment (DCB or DES) and the small vessel disease subgroup was 0.02).

“DCB angioplasty failed to achieve noninferiority compared to standard treatment with second-generation, thin-strut, DESs, mainly due to the need for more repeat procedures (revascularization),” commented Dr. Tao in the ESC press release.

Dr. Tao continued, “While PCI with DES is highly effective, 2% of patients experience in-stent restenosis annually after the procedure. Because of the metallic scaffold left behind, a DES may distort and permanently cage the coronary vessel from adaptive remodeling, impeding vessel pulsatility, interfering with cell signaling and mechano-transduction, and promoting chronic inflammation. Such stent-related adverse events have fueled interest in alternative stent-free methods of local drug delivery, such as using DCBs.”

Finally, Dr Tao stated, “Our results show that the attempted strategy of ‘leave nothing behind’ by using paclitaxel-coated balloons in de novo noncomplex CAD was disproven, and DES implantation should continue to be the standard of care for these patients.”

The 2-year findings from the REC-CAGEFREE I trial were recently published by Professor Chao Gao, PhD, et al online ahead of print in The Lancet.