Abstract
BACKGROUND: The anatomical and pathophysiological characteristics of coronary artery disease vary between the sexes. This study investigated the impact of sex on outcomes in patients with de novo coronary artery lesions treated with drug-coated balloons (DCB) or drug-eluting stents (DES). METHODS: REC-CAGEFREE I was an investigator-initiated, non-inferiority trial conducted at 43 sites in China from Feb 5, 2021, to May 1, 2022, which randomized 2,272 patients for treating de novo coronary lesions, regardless of vessel diameter. After successful lesion pre-dilatation, eligible patients were randomized (1:1) to either DCB angioplasty with the option of rescue stenting or intended DES deployment. In this prespecified subgroup analysis, patients were analyzed by sex based on their medical records. The primary endpoint was device-oriented composite endpoint (DoCE), including cardiovascular death, target-vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization at 2 years. Between-group differences were compared by Cox proportional-hazards models, and imbalances in baseline characteristics were adjusted with inverse probability of treatment weighting (IPTW). The analyses were conducted in the intention-to-treat population. RESULTS: A total of 2,272 participants underwent randomization, of which 698 (30.7%) were female and 1,574 (69.3%) were male. At 2 years, no statistically significant differences in the incidence of DoCE were observed between sexes (36 [5.2%] for females and 74 [4.7%] for males, HR(IPTW):1.04, 95%CI:0.67 to 1.61, P = 0.877). Compared with DES, DCB was associated with a numerically higher risk of DoCE in females (6.3% versus 3.9%, HR(IPTW):1.55, 95%CI:0.78 to 3.11, P = 0.210) and a statistically significant higher risk in males (6.4% versus 3.1%, HR(IPTW):2.28, 95%CI:1.40 to 3.70, P = 0.001), respectively, with no significant sex-by-treatment (DCB/DES) interaction observed (P(interaction) = 0.575). The prognosis of DCB and DES differed significantly between small vessel disease (SVD) and non-SVD among females (P(interaction) = 0.007), but not among males (P(interaction) = 0.408). CONCLUSIONS: For patients with de novo, non-complex coronary artery disease, DCB was associated with a significantly higher risk of 2-year DoCE compared with DES in males, whereas a consistent but non-significant trend was observed in females. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04561739.