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.

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Study queStionWhat is the most safe and effective interventional treatment for coronary in-stent restenosis? MethodSIn a hierarchical Bayesian network meta-analysis, PubMed, Embase, Scopus, Cochrane Library, Web of Science, ScienceDirect, and major scientific websites were screened up to 10 August 2015. Randomised controlled trials of patients with any type of coronary in-stent restenosis (either of bare metal stents or drug eluting stents; and either first or recurrent instances) were included. Trials including multiple treatments at the same time in the same group or comparing variants of the same intervention were excluded. Primary endpoints were target lesion revascularisation and late lumen loss, both at six to 12 months. The main analysis was complemented by network subanalyses, standard pairwise comparisons, and subgroup and sensitivity analyses. Study anSwer and liMitationSTwenty four trials (4880 patients), including seven interventional treatments, were identified. Compared with plain balloons, bare metal stents, brachytherapy, rotational atherectomy, and cutting balloons, drug coated balloons and drug eluting stents were associated with a reduced risk of target lesion revascularisation and major adverse cardiac events, and with reduced late lumen loss. Treatment ranking indicated that drug eluting stents had the highest probability (61.4%) of being the most effective for target lesion vascularisation; drug coated balloons were similarly indicated as the most effective treatment for late lumen loss (probability 70.3%). The comparative efficacy of drug coated balloons and drug eluting stents was similar for target lesion revascularisation (summary odds ratio 1.10, 95% credible interval 0.59 to 2.01) and late lumen loss reduction (mean difference in minimum lumen diameter 0.04 mm, 95% credible interval −0.20 to 0.10). Risks of death, myocardial infarction, and stent thrombosis were comparable across all treatments, but these analyses were limited by a low number of events. Trials had heterogeneity regarding investigation periods, baseline characteristics, and endpoint reporting, with a lack of information at long term follow-up. Direct and indirect evidence was also inconsistent for the comparison between drug eluting stents and drug coated balloons. what thiS Study addSCompared with other currently available interventional treatments for coronary in-stent restenosis, drug coated balloons and drug eluting stents are associated with superior clinical and angiographic outcomes, with a similar comparative efficacy.

In patients undergoing percutaneous coronary procedures, statin administration is associated with a marked and consistent reduction in the risk of CIAKI compared with saline. Although xanthine, NAC, NaHCO, NAC+NaHCO, ischemic preconditioning, and natriuretic peptide may have nephroprotective effects, these results were not consistent across multiple sensitivity analyses.

URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00433966 (HORIZONS-AMI) and ACUITY (NCT00093158).

Aims After percutaneous coronary intervention (PCI) with second-generation drug-eluting stent (DES), whether short dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) with a P2Y12 receptor inhibitor confers benefits compared with prolonged DAPT is unclear. Methods and results Multiple electronic databases, including PubMed, Scopus, Web of Sciences, Ovid, and ScienceDirect, were searched to identify randomized clinical trials comparing ≤3 months of DAPT followed by P2Y12 inhibitor SAPT vs. 12 months of DAPT after PCI with second-generation DES implantation. The primary and co-primary outcomes of interest were major bleeding and stent thrombosis 1 year after randomization. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by fixed-effect and random-effects models. Multiple sensitivity analyses including random-effects models 95% CI adjustment were applied. A sensitivity analysis comparing trials using P2Y12 inhibitor SAPT with those using aspirin SAPT was performed. A total of five randomized clinical trials (32 145 patients) were available. Major bleeding was significantly lower in the patients assigned to short DAPT followed by P2Y12 inhibitor SAPT compared with those assigned to 12-month DAPT (random-effects model: HR 0.63, 95% 0.45–0.86). No significant differences between groups were observed in terms of stent thrombosis (random-effects model: HR 1.19, 95% CI 0.86–1.65) and the secondary endpoints of all-cause death (random-effects model: HR 0.85, 95% CI 0.70–1.03), myocardial infarction (random-effects model: HR 1.05, 95% CI 0.89–1.23), and stroke (random-effects model: HR 1.08, 95% CI 0.68–1.74). Sensitivity analyses showed overall consistent results. By comparing trials testing ≤3 months of DAPT followed by P2Y12 inhibitor SAPT vs. 12 months of DAPT with trials testing ≤3 months of DAPT followed by aspirin SAPT vs. 12-month of DAPT, there was no treatment-by-subgroup interaction for each endpoint. By combining all these trials, regardless of the type of SAPT, short DAPT was associated with lower major bleeding (random-effects model: HR 0.63, 95% CI 0.48–0.83) and no differences in stent thrombosis, all-cause death, myocardial infarction, and stroke were observed between regimens. Conclusion After second-generation DES implantation, 1–3 months of DAPT followed by P2Y12 inhibitor SAPT is associated with lower major bleeding and similar stent thrombosis, all-cause death, myocardial infarction, and stroke compared with prolonged DAPT. Whether P2Y12 inhibitor SAPT is preferable to aspirin SAPT needs further investigation.

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