Paclitaxel-coated balloon angioplasty vs. drug-eluting stenting for the treatment of coronary in-stent restenosis: a comprehensive, collaborative, individual patient data meta-analysis of 10 randomized clinical trials (DAEDALUS study)

Abstract

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.

Keywords: Clinical Trials; Drug-coated balloon; Drug-eluting stent; In-stent restenosis; Meta-analysis; Mortality; Paclitaxel; Percutaneous coronary intervention.

Graphical Abstract

Figure 1

Primary efficacy endpoint (target lesion revascularization). Cumulative incidence of primary efficacy endpoint in patients allocated to angioplasty with paclitaxel-coated balloon vs. repeat stenting with drug-eluting stent. The upper panel shows the results of the one-stage analysis. The lower panel shows the results of the two-stage analysis. CI, confidence interval; DES, drug-eluting stent; HR, hazard ratio; HR_adj, adjusted hazard ratio; n, number of patients with event; N, number of patients assigned to the treatment; PCB, paclitaxel-coated balloon. The numbers of patients at risk in the treatment groups are shown below the graphs.

Figure 2

Subgroup analysis for the primary efficacy endpoint. ACS, acute coronary syndrome; BMS, bare-metal stent; CAD, coronary artery disease; CI, confidence interval; DES, drug-eluting stent; HR, hazard ratio; ISR, in-stent restenosis; MLD, minimum lumen diameter; n, number of patients with event; N, number of patients assigned to the treatment; RVD, reference vessel diameter.

Figure 3

Primary safety endpoint (all-cause death, myocardial infarction, or target lesion thrombosis). Cumulative incidence of primary safety endpoint in patients allocated to angioplasty with paclitaxel-coated balloon vs. repeat stenting with drug-eluting stent. The upper panel shows the results of the one-stage analysis. The lower panel shows the results of the two-stage analysis. CI, confidence interval; DES, drug-eluting stent; HR, hazard ratio; HR_adj, adjusted hazard ratio; n, number of patients with event; N, number of patients assigned to the treatment; PCB, paclitaxel-coated balloon. The numbers of patients at risk in the treatment groups are shown below the graphs.

Figure 4

Subgroup analysis for the primary safety endpoint. ACS, acute coronary syndrome; BMS, bare-metal stent; CAD, coronary artery disease; CI, confidence interval; DES, drug-eluting stent; HR, hazard ratio; ISR, in-stent restenosis; MLD, minimum lumen diameter; n, number of patients with event; N, number of patients assigned to the treatment; RVD, reference vessel diameter.

Figure 5

(A) All-cause death, (B) cardiac death, (C) non-cardiac death, for paclitaxel-coated balloon vs. drug-eluting stent, and (D) mortality after paclitaxel-coated balloon vs. non-paclitaxel-eluting stent. Incidence and type of death in patients allocated to angioplasty with paclitaxel-coated balloon vs. repeat stenting with drug-eluting stent (A–C) and paclitaxel-coated balloon vs. non-paclitaxel-eluting stent (D). CI, confidence interval; DES, drug-eluting stent; HR, hazard ratio; HR_adj, adjusted hazard ratio; PCB, paclitaxel-coated balloon. The numbers of patients at risk in the treatment groups are shown below the graphs.

Take home figure

Summary of the treatment effects for angioplasty with paclitaxel-coated balloon vs. repeat stenting with drug-eluting stent in patients treated for coronary in-stent restenosis. ^aPrimary efficacy endpoint was target lesion revascularization; ^bprimary safety endpoint was the composite of death, myocardial infarction, or target lesion thrombosis; ^cnet composite endpoint 1 refers to the composite of death, myocardial infarction, target lesion thrombosis, or target lesion revascularization; ^dnet composite endpoint 2 refers to the composite of death, myocardial infarction, target lesion thrombosis, or target vessel revascularization.