Paclitaxel drug coated balloons (DCB) for percutaneous treatment of coronary artery disease (CAD) are not associated with increased mortality, and longer term evaluation suggests a trend towards lower mortality compared to control therapies. The authors of a meta-analysis of randomised controlled trials, published in the Journal of the American College of Cardiology, say the findings are “in contrast to reported experience with paclitaxel-coated devices for superficial femoral artery interventions” and that the data “reassure the safety of these devices when used in coronary arteries”.
Bruno Scheller (University of Saarland, Homburg/Saar, Germany) et al compared DCB with non-DCB devices (such as conventional balloon angioplasty and bare-metal stents [BMS] with drug-eluting stents [DES]) for the treatment of coronary in-stent restenosis or de novo lesions. Following a meta-analysis in December 2018 by Katsanos et al that reported an increased mortality in trials with two or more years of follow-up after combining treatments with paclitaxel-coated stents or balloons in peripheral artery disease (PAD), and which Scheller et al say led to “major uncertainty in the clinical community”, they undertook to investigate the available data on survival after coronary intervention with paclitaxel-coated balloons from randomised controlled trials (RCTs) on PubMed, Web of science, and the Cochrane library database, “as no previous coronary studies were powered to assess the risk of long-term mortality appropriately”.
The primary outcome was all-cause mortality. The number of patients lost to follow-up was observed at different timepoints. A total of 4,590 patients enrolled in 26 RCTs published between 2006 and 2019 were analysed. At follow-up of six to 12 months (n=4,590, 26 RCTs), no significant difference in all-cause mortality was seen; however, DCB treatment was associated with a numerically lower mortality risk (risk ratio [RR] 0.74, 95% confidence interval [CI] 0.51–1.08, p=0.116). Risk of death at two years (n=1,477, eight RCTs) was similar between the two groups (RR 0.84, 95% CI 0.51–1.37, p=0.478). After three years of follow-up (n=1,775, nine RCTs), all-cause mortality was significantly lower in the DCB group when compared with control treatment (RR 0.73, 95% CI 0.53–1.00, p=0.047), with a number needed to treat of 36 to prevent one death. A similar reduction was seen in cardiac mortality (RR 0.53, 95% CI 0.33–0.85, p=0.009).
On the finding of a 27% relative risk reduction in all-cause mortality after three years, Scheller and colleagues speculate that this is related to a “significant reduction in the number and length of permanent implants, which should lead to a reduction in stent-associated short- and long-term events”. In addition, they say: “Appropriate lesion preparation may help identify lesions at risk that require stent treatment” A further factor, they suggest, is that local drug application reduces the restenosis probability comparable to the same order of magnitude as DES.
The researchers also report a subgroup analysis of the study which compared treatment with paclitaxel via DCB versus treatment without local drug administration (balloon angioplasty or BMS) and found a survival advantage for local paclitaxel application as early as one year. Furthermore, they say, reduced rates of cardiac mortality at three years following DCB treatment were also observed when paclitaxel eluting stents as control treatment were excluded.
Among the strengths and limitations that they highlight are that the analysis considered patient numbers lost to follow-up at different time points, although it was conducted at a study rather than a patient level. To achieve the best possible data quality, the researchers involved the principal investigators of most of the included trials. Most of the studies were powered for surrogate angiographic endpoints. They also point out that the majority of available studies using non-iopromide-coated balloons were small (apart from the iopromide paclitaxel DCB), which limited the possibility of conducting additional analysis comparing different DCB technologies. Furthermore, crossover treatment could not be assessed systematically, because this information was not provided in most of the publications. Additionally, information on concomitant medication, such as antiplatelet and statin therapy, was incompletely available and could therefore not be investigated.
Scheller and colleagues also concede: “Advances in stent design and evolution of comedication regimens, especially of the ones used in earlier studies, could be associated with improved outcomes and may have influenced the findings.” They call for additional long-term follow-up data “to confirm whether a survival advantage associated with DCB-based therapy should change the priority of primary stent deployment in patients undergoing PCIs [percutaneous coronary interventions]”.