Background Persistent non-plateauing adverse event rates in patients who underwent percutaneous coronary intervention (PCI) remain a challenge. A bioadaptor is a novel implant that addresses this issue by restoring the haemodynamic modulation of the artery, allowing cyclic pulsatility, vasomotion, and adaptative remodelling, by unlocking and providing dynamic support to the artery. We aimed to assess outcomes with the device versus a contemporary drug-eluting stent (DES) in a representative PCI population. Methods INFINITY-SWEDEHEART is a single-blind, non-inferiority, registry-based, randomised controlled study conducted in 20 hospitals in Sweden. Patients aged 18-85 years, with chronic or acute coronary syndrome ischaemic heart disease, with an indication for PCI, with up to three de novo lesions suitable for implantation with one single device per lesion, and successful pre-dilatation were identified via the Swedish Coronary Angiography and Angioplasty Registry and eligible for enrolment. Participants were randomly assigned (1:1), using block randomisation with random variation in block size and stratified by site, to either the DynamX bioadaptor (Elixir Medical, Milpitas, CA, USA) or a zotarolimus-eluting DES (Resolute Onyx and Onyx Trustar, Medtronic, Minneapolis, MN, USA). The primary endpoint was the device-oriented clinical endpoint of target lesion failure at 12 months (a composite of cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target lesion revascularisation), assessed in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment, regardless of treatment received) who had either experienced an event up to 12 months or completed the trial up to 12 months. Non-inferiority was established if the upper limit of the two-sided 95% CI for the absolute risk difference was less than 4 center dot 2%. Powered secondary endpoints were landmark analyses from 6 months onwards for target lesion failure, target vessel failure (composite of cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target vessel revascularisation), and target lesion failure for patients with acute coronary syndrome assessed in the ITT population). This study is registered with ClinicalTrials.gov, NCT04562805, and follow-up to 5 years is ongoing. Findings Between Sept 30, 2020, and July 11, 2023, 2399 patients were randomly assigned to receive the bioadaptor (n=1201) or DES (n=1198; ITT population). Median age was 69 center dot 5 years (IQR 61 center dot 2-75 center dot 6), 575 (24 center dot 0%) of 2399 patients were female, and 1824 (76 center dot 0%) were male (data on race and ethnicity were not collected), and 1838 (76 center dot 6%) patients presented with acute coronary syndrome. The primary endpoint of 12-month target lesion failure occurred in 28 (2 center dot 4%) of 1189 assessable patients in the bioadaptor group versus 33 (2 center dot 8%) of 1192 assessable patients in the DES group, with a risk difference of -0 center dot 41% (95% CI -1 center dot 94 to 1 center dot 11; p(non-inferiority)<0 center dot 0001). In the prespecified landmark analysis from 6 months to 12 months, the Kaplan-Meier estimates of target lesion failure were 0 center dot 3% (with events in three of 1170 patients) in the bioadaptor group versus 1 center dot 7% (with events in 16 of 1176 patients) in the DES group (hazard ratio 0 center dot 19 [95% CI 0 center dot 06 to 0 center dot 65]; p=0 center dot 0079), of target vessel failure were 0 center dot 8% (events in eight of 1167) versus 2 center dot 5% (events in 23 of 1174; 0 center dot 35 [0 center dot 16 to 0 center dot 79]; p=0 center dot 011), and of target lesion failure in patients with acute coronary syndrome were 0 center dot 3% (events in two of 906) versus 1 center dot 8% (events in 12 of 895; 0 center dot 17 [0 center dot 04 to 0 center dot 74]; p=0 center dot 018). The rate of definite or probable device thrombosis, which was recorded as a safety outcome, was low and did not differ between groups (eight [0 center dot 7%] of 1201 in the bioadaptor group vs six [0 center dot 5%] of 1198 in the DES group; difference in event rates of 0 center dot 16% [95% CI -0 center dot 50 to 0 center dot 83]). Interpretation Among patients with coronary artery disease, including those with acute coronary syndrome, treatment with the bioadaptor was non-inferior to contemporary DES, showing potential to mitigate non-plateauing devicerelated events and improving outcomes in patients undergoing PCI. The additional planned follow-up will help to reinforce the clinical significance of the 1-year findings. Copyright (c) 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.