AIMS: Consensus is lacking regarding the best treatment for coronary in-stent restenosis (ISR). The two most effective treatments are angioplasty with paclitaxel-coated balloon (PCB) and repeat stenting with drug-eluting stent (DES) but individual trials were not statistically powered for clinical endpoints, results were heterogeneous, and evidence about comparative efficacy and safety in relevant subsets was limited. METHODS AND RESULTS: The Difference in Anti-restenotic Effectiveness of Drug-eluting stent and drug-coated balloon AngiopLasty for the occUrrence of coronary in-Stent restenosis (DAEDALUS) study was a comprehensive, investigator-initiated, collaborative, individual patient data meta-analysis comparing angioplasty with PCB alone vs. repeat stenting with DES alone for the treatment of coronary ISR. The protocol was registered with PROSPERO (CRD42017075007). All 10 available randomized clinical trials were included with 1976 patients enrolled, 1033 assigned to PCB and 943 to DES. At 3-year follow-up, PCB was associated with a significant increase in the risk of target lesion revascularization (TLR) compared with DES [hazard ratio (HR) 1.32, 95% CI 1.02–1.70, P = 0.035; number-needed-to-harm 28.5]. There was a significant interaction between treatment effect and type of restenosed stent (P = 0.029) with a more marked difference in patients with DES-ISR and comparable effects in patients with bare-metal stent-ISR. At 3-year follow-up, the primary safety endpoint of all-cause death, myocardial infarction, or target lesion thrombosis was comparable between treatments (HR 0.80, 95% CI 0.58–1.09, P = 0.152). A pre-specified subgroup analysis indicated a significant interaction between treatment effect and type of DES used to treat ISR (P = 0.033), with a lower incidence of events associated with PCB compared with first-generation DES and similar effect between PCB and second-generation DES (HR 1.06, 95% CI 0.71–1.60, P = 0.764). Long-term all-cause mortality was similar between PCB and DES (HR 0.81, 95% CI 0.53–1.22, P = 0.310); results were consistent comparing PCB and non-paclitaxel-based DES (HR 1.42, 95% CI 0.80–2.54, P = 0.235). Myocardial infarction and target lesion thrombosis were comparable between treatments. CONCLUSIONS: In patients with coronary ISR, repeat stenting with DES is moderately more effective than angioplasty with PCB at reducing the need for TLR at 3 years. The incidence of a composite of all-cause death, myocardial infarction, or target lesion thrombosis was similar between groups. The rates of individual endpoints, including all-cause mortality, were not significantly different between groups.

Daiichi Sankyo 211 Mt Airy Road 07920 Basking Ridge NJ USA

Department of Cardiology Academic Medical Centre University of Amsterdam Meibergdreef 9 1105 Amsterdam the Netherlands

Department of Cardiology Asan Medical Center University of Ulsan 388 1 Poongnapdong Seoul 138 736 South Korea

Department of Cardiology Contilia Heart and Vascular Center Elisabeth Krankenhaus Klara Kopp Weg 1 45138 Essen Germany

Department of Cardiology Fu Wai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences 167 Beilishi Road Xicheng 100037 Beijing China

Department of Cardiology Herz Kreislauf Zentrum Heinz Meise Strasse 100 36199 Rotenburg an der Fulda Germany

Department of Cardiology Hospital Clinico San Carlos Calle Profesor Martin Lagos 28040 Madrid Spain

Department of Cardiology Hospital Universitario de La Princesa Madrid Calle Diego de León 62 Madrid 28006 Spain

Department of Cardiology University Hospital Ostrava tr 17 listopadu 1790 70852 Ostrava Czech Republic

Department of Cardiovascular Diseases Deutsches Herzzentrum München Technische Universität München Lazarettstrasse 36 80636 Munich Germany

Department of Cardiovascular Diseases University Hospitals Leuven Herestraat 49 3000 Leuven Belgium

DZHK Munich Heart Alliance Marchioninistrasse 15 81377 Munich Germany

Mount Sinai Heart the Zena and Michael Wiener Cardiovascular Institute Icahn School of Medicine at Mount Sinai 1428 Madison Avenue 10029 New York NY USA

Eur Heart J. 2020 Oct 7;41(38):3729-3731. doi: 10.1093/eurheartj/ehz731. PubMed

Eur Heart J. 2020 Oct 7;41(38):3728. doi: 10.1093/eurheartj/ehz861. PubMed

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