Paclitaxel-coated balloon angioplasty vs. drug-eluting stenting for the treatment of coronary in-stent restenosis

Selected in the European Heart Journal by J. Bil , D. Milasinovic

A comprehensive, collaborative, individual patient data meta-analysis of 10 randomized clinical trials (DAEDALUS study)

Reviewers

Jacek Bil

Interventional cardiologist / Cardiologist

Centre of Postgraduate Medical Education - Warsaw, Poland

Dejan Milasinovic

@MilasinD18

Interventional cardiologist / Cardiologist

Clinical Centre of Serbia - Belgrade, Serbia

Our Comment

This joint review is part of the PCRonline GLOBAL Journal Club Initiative by selected members of the EAPCI/PCR Journal Club and PCR NextGen, and is based on the underlying idea of “Bringing peers together, exchanging ideas, towards a common standard of care”.

Why this study – the rationale/objective?

There is no consensus regarding the best treatment for coronary in-stent restenosis (ISR), the two most commonly used options being angioplasty with paclitaxel-coated balloon (PCB) and repeat stenting with a drug-eluting stent (DES). The here presented meta-analysis of individual patient data from 10 randomized clinical trials compared clinical effects of angioplasty with PCB vs. repeat stenting with DES in patients with ISR.

How was it executed – the methodology?

• 1976 patients were enrolled, 1033 assigned to PCB and 943 to DES.
• The primary efficacy endpoint was target lesion revascularization (TLR), including any revascularization, either percutaneous or surgical, at the target segment (i.e. in-segment ISR). 
• The primary safety endpoint was a combination of all-cause death, myocardial infarction (MI) or target lesion thrombosis.

What is the main result?

At 3-year follow-up:

• PCB was associated with a significant increase in the rate of TLR compared with DES (16% vs. 12%, HR 1.32, 95% CI 1.02–1.70, P = 0.035).
• Subgroup analysis revealed a significant interaction (p=0.029) of the type of the restenotic stent on the treatment effect, in a way that PCB was not inferior to DES in the underlying BMS-ISR, but mainly in patients with DES-ISR (HR 1.6, p=0.002). 
• The combined occurrence of all-cause death, MI or target lesion thrombosis was comparable between treatment arms (9% in the PCB group vs. 10.9% in DES; HR 0.80, 95% CI 0.58–1.09, P = 0.152). 
• Subgroup analysis indicated a significant interaction between treatment effect and the type of DES used to treat ISR (P = 0.033), with a lower incidence of adverse events associated with PCB when compared with 1st-generation DES, and no difference when PCB was compared with 2nd-generation DES.

Critical reading and the relevance for clinical practice

Although newer generation DES led to significant decrease in ISR incidence, randomized clinical trials comparing contemporary devices showed TLR rates of 7-10% at 5-year follow-up, which highlights the importance of defining adequate treatment strategies in cases of stent failure.

The pooling of close to 2000 individual patients in the DADALUS study created the hitherto largest pool of randomized data showing that in patients with ISR (and more so DES-ISR), implanting a new DES may be more efficacious compared with a PCB, while maintaining similar safety up to 3 years follow-up.

This being said, it needs to be noted that the pooled finding of the lower TLR rate with DES compared with PCB was burdened by at least a moderate between-study heterogeneity. In addition, it should be kept in mind that the role of intracoronary imaging has not been addressed in this analysis, although it could be an important source of information regarding the mechanisms of stent failure and the morphology of the restenotic tissue, and thus play a role in defining the treatment strategy in individual cases.

In summary, this individual patient data meta-analysis appears to lend support to the use of 2nd generation DES in treating DES failure, with no penalty in terms of safety up to 3 years.