A randomized comparison of paclitaxel-eluting balloon versus everolimus-eluting stent for the treatment of any in-stent restenosis: The DARE Trial
Selected in JACC: Cardiovascular Interventions by D. Milasinovic
Baan J Jr., Claessen BE, Dijk KB, Vendrik J, van der Schaaf R, Meuwissen M, van Royen N, Gosselink ATM, van Wely MH, Dirkali A, Arkenbout EK, de Winter RJ, Koch KT, Sjauw KD, Beijk MA, Vis MM, Wykrzykowska JJ, Piek JJ, Tijssen JGP, Henriques JPS
JACC Cardiovasc Interv. 2018 Feb 12;11(3):275-283
LinkRead the abstract
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Why this study – the rationale/objective?
Previous randomized trials (e.g. RIBS IV and V) indicated potential superiority of a new generation DES over a drug-eluting balloon (DEB) for treatment of in-stent restenosis (ISR). The DARE randomized study compared a DEB (SeQuent Please that is coated with paclitaxel) versus everolimus-eluting stent (EES, Xience) in a mixed population of patients with BMS or DES ISR.
How was it executed – the methodology?
- 278 patients were randomized to receive either PEB (n=137) or EES (n=141), of which 77% and 82%, respectively, underwent the 6-month follow-up angiography, whereas all enrolled patients were available for the clinical follow-up at 1 year.
- The study was designed to address non-inferiority of PEB vs. EES for the primary endpoint of in-segment minimal lumen diameter (MLD) at 6 months.
What is the main result?
- At 6 months, in-segment MLD was not significantly different between the groups (PEB 1.71±0.51 mm vs. EES 1.74±0.61 mm; p=0.65, p for non-inferiority <0.001).
- Immediate post-procedural angiographic result tended to favor EES over PEB (in-segment acute gain 1.06 mm vs. 0.97 mm, p=0.12), whereas late lumen loss (LLL) was larger in the EES group (0.45 mm vs. 0.17 mm, p<0.001).
- At 12 months, the rates of death, MI and target vessel revascularization were similar between the groups. No cases of stent thrombosis were reported in neither group.
Critical reading and the relevance for clinical practice
The here described data from the DARE trial broaden the existing evidence base regarding the treatment of ISR, although it needs to be kept in mind, that unlike most of the other trials in the field, it included a mixed patient population (≈55% DES ISR and ≈45% BMS ISR). The demonstrated non-inferiority of a DEB vs. EES seems to provide support for the results of earlier studies (ISAR-DESIRE 3, PEPCAD China ISR), that compared the same DEB (SeQuent Please) with the 1st generation paclitaxel-eluting stent, as well as to go in line with the recently published data from the RESTORE trial (Am Heart J. 2018 Mar;197:35-42), which also indicated non-inferiority of DEB to EES (although the trial was underpowered due to slow recruitment). Importantly, the notion of treating ISR without leaving behind an additional layer of metallic struts appears to intuitively provide an attractive concept that may reduce long-term ischemic risks.
However, it should be kept in mind that two recent randomized trials (RIBS IV in DES ISR and RIBS V in BMS ISR) showed both angiographic (increase in MLD) and clinical (reduction in revascularization rates) benefits of EES over DEB. The observed benefit seemed to have, in large part, been derived from better acute procedural results, if ISR was treated with an implantation of another stent (EES), as compared with a balloon angioplasty (DEB). Interestingly, in the here presented DARE trial, the larger acute gain with EES was offset by the larger LLL at 6 months. It may also be noted that in-lesion QCA revealed a larger 6-month MLD for EES over DEB (1.98mm vs. 1.79mm, p=0.02), contrary to the similar in-segment MLD between the groups, that was the study’s pre-specified primary endpoint.
Overall, there seem to be at least three important questions that may warrant further studies in this field. First, what are the long-term outcomes of DEB vs. DES, in terms of the risks of future ischemic events. Second, what may be the role of intravascular imaging as a potential tool to tailor the treatment according to the underlying ISR mechanism. Third, since a class-effect of DEB has not been assumed, are there any clinically meaningful differences in outcomes among different devices.
In light of the hitherto collected randomized data, what is your current treatment algorithm for patients with ISR?