Drug-Coated Balloons for Small Coronary Artery Disease

Abstract

Background: Drug-coated balloons (DCB) are a novel therapeutic strategy for small native coronary artery disease. However, their safety and efficacy as compared to drug-eluting stents (DES) is poorly defined. Methods: In a multicenter, randomized non-inferiority trial, 758 patients with de-novo lesions in coronary vessels <3mm and an indication for percutaneous coronary intervention were randomized 1:1 to angioplasty with DCB vs. implantation of a second-generation DES after successful predilatation. The primary objective of this trial was to demonstrate non-inferiority of DCB vs. DES regarding major adverse cardiac events (MACE, i.e., cardiac death, non-fatal myocardial infarction, and target-vessel revascularization) after 12 months. The non-inferiority margin was set at an absolute rate difference of 4%. Dual antiplatelet therapy was given according to current guidelines. Findings: Non-inferiority of DCB vs. DES was demonstrated since the 95% confidence interval of the absolute difference in MACE was below the predefined margin (-3·84, 3·89%, p=0·02). After 12 months, event rates were similar in both groups (DCB vs. DES; MACE 7·6 vs. 7·5%, p=0·92) without any statistical difference for the single components of the primary endpoint (DCB vs. DES; cardiac death 3·1 vs. 1·3%, p=0·11; non-fatal myocardial infarction 1·6 vs. 3·5%, p=0.11; target vessel revascularization 3·4 vs. 4·5%, p=0·44). Interpretation: In small native coronary artery disease, DCB was non-inferior to DES regarding MACE up to 12 months, with similar event rates for both treatment groups. Trial Registration Number: NCT01574534 on clinicaltrials.gov Funding Statement: Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung, Bern, Switzerland (32003B_140956); Basel Cardiovascular Research Foundation, Basel, Switzerland; and B. Braun Medical AG, Sempach, Switzerland. Declaration of Interest: RJ has received lecture honoraria and travel support from B.Braun. MAO has received proctoring honoraria and travel support from Biosensors and research support from Terumo. NM has received speaker´s honoraria from Edwards and Medtronic, and consultant honoraria from Biotronik. GL is a medical user advisory board member for REVA Medical and has relationships with drug and device companies including Terumo, Acrostak, Bionsensors, Boston Scientific, Abbott Vascular, Impuls Medical, and Orbus Neich. FM is supported by Deutsche Gesellschaft fur Kardiologie, Deutsche Hochdruckliga, and Deutsche Forschungsgemeinschaft (SFB TRR 219), and has received grant support and personal fees from Medtronic and Recor Medical. AL has received speaker honoraria or served as a consultant for the following companies: Medtronic, St. Jude Medical, Claret Medical Inc., Boston Scientific, Edwards Lifesciences, Symetis, and Bard, and holds stock options from Claret Medical Inc., Emboline and Transverse Medical. In addition, he received grant support from Medtronic and Claret Medical Inc. and speaker honoraria from Novartis and Bayer. NG has received travel support from B.Braun. BS is shareholder of InnoRa GmbH, Berlin, and was named as co-inventor on patent applications submitted by Charite university hospital, Berlin, Germany. The other authors declare no other conflict of interest. Ethics Approval Statement: The trial was performed in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines, and the protocol was approved by the ethics committees in all participating centers (names of centers are listed in 6.2 of Appendix).