Author + information
- Received April 19, 2016
- Revision received May 26, 2016
- Accepted June 2, 2016
- Published online August 22, 2016.
- Daniele Giacoppo, MDa,
- Salvatore Cassese, MD, PhDa,
- Yukinori Harada, MDa,
- Roisin Colleran, MBChBa,
- Jonathan Michel, MBBSa,
- Massimiliano Fusaro, MDa,
- Adnan Kastrati, MDa,b and
- Robert A. Byrne, MBChB, PhDa,∗ ()
- aDeutsches Herzzentrum München, Technische Universität München, Munich, Germany
- bDZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
- ↵∗Reprint Requests and Correspondence:
Dr. Robert Byrne, Deutsches Herzzentrum München, Lazarettstrasse 36, 80636, Munich, Germany.
Objectives This study sought to assess the risk of target lesion revascularization (TLR) and all-cause death at 12 months and at the maximum available follow-up. Secondary objectives included the identification of factors which could have influenced general findings.
Background Recently several randomized trials comparing drug-coated balloon (DCB) with conventional plain balloon (PB) for the treatment of femoropopliteal artery disease have been reported, but no updated meta-analyses are available and questions remain surrounding the long-term antirestenotic effectiveness of the 2 therapies.
Methods We searched main electronic databases for randomized trials comparing DCB and PB for femoropopliteal artery disease. Random effects models were used to estimate the risk of TLR and all-cause death at 12 months, whereas long-term TLR and death risk were assessed by mixed effects Poisson regression models and incident rates of each outcome per patient-year. Main analyses were supplemented by sensitivity analyses, Bayesian estimates, and trial sequential analysis.
Results A total of 8 eligible trials were identified. DCB was associated with a marked 12-month TLR risk reduction as compared with PB (risk ratio: 0.33; 95% confidence interval [CI]: 0.19 to 0.57). The risk of death was similar between groups (risk ratio: 0.96; 95% CI: 0.47 to 1.95). Long-term outcomes assessment showed a reduced incidence of TLR with DCB (0.35; 95% CI: 0.24 to 0.51) and a similar incidence of all-cause death (incidence rate ratio: 1.13; 95% CI: 0.60 to 2.15). Similar findings were observed in Bayesian analyses. Significant heterogeneity was present with evidence of differential efficacy across devices. Trial sequential analysis indicated that available evidence is sufficient to prove superior antirestenotic efficacy of DCB over PB.
Conclusions DCB significantly reduces the risk of TLR as compared with PB without any effect on all-cause death. Evidence exists for differential efficacy according to the type of device used. Future trials investigating DCB angioplasty should include potentially more effective comparator therapies.
Substantial improvements in endovascular techniques and outcomes mean that percutaneous transluminal angioplasty is now the first-line revascularization strategy for patients with symptomatic peripheral arterial disease (1). Plain balloon (PB) angioplasty for femoropopliteal artery disease has a high rate of procedural success and an acceptable safety profile, however, rates of restenosis are considerable (2). For this reason, a number of alternative percutaneous treatment strategies have been investigated (3–8).
Drug-coated balloons (DCBs) are standard balloon angioplasty catheters surface coated with a thin layer of antiproliferative drug combined with an excipient or spacer substance, which facilitates drug transfer to the vessel wall (9). The advantages of DCB therapy include drug delivery and inhibition of neointimal proliferation without requirement for a permanent metallic implant, more uniform drug–tissue transfer, potential amelioration of vessel healing due to the absence of proinflammatory durable polymer surface coating, and preservation of arterial regulatory functions (9).
Recently, several randomized clinical trials comparing DCB with conventional PB angioplasty for the treatment of femoropopliteal artery disease have been reported but no updated meta-analyses are available and data relating to the long-term assessment of the 2 therapies is scant (10–12). In addition, there continues to be ongoing discussion of the usefulness of systematic use of DCB instead of PB for de novo lesions and results obtained with different DCBs may be not uniform (13). Against this background, we conducted a comprehensive meta-analysis of randomized clinical trials comparing DCB versus PB for the treatment of femoropopliteal artery disease with the primary objective to assess the treatment effect for need for repeat target lesion revascularization (TLR) and death at 12 months and at the longest available follow-up. Secondary aims were the assessment of trial-level factors that could have influenced the antirestenotic effectiveness of the 2 devices and introduced heterogeneity, the exploration of the potential differential efficacy among available types of DCB, and the definition of functional benefits of a DCB-based revascularization.
This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Cochrane’s Collaboration recommendations (14,15). The PRISMA checklist is reported in the Online Appendix. Data used were from intention-to-treat analyses. Statistical analyses were performed using R (version 3.2.3), WinBUGS (version 1.4.3), and TSA (version 0.9).
Literature search and study selection
We searched PubMed, ScienceDirect, Scopus, Web of Knowledge, and Cochrane Library electronic databases for randomized trials comparing DCB versus PB for the treatment of femoropopliteal artery disease from the date of inception to December 1, 2015. No language restrictions or specific clinical subsets were imposed. The search algorithm applied for trials identification and the corresponding results are reported in the Online Table 1. Tangential exploration of relevant scientific websites (Online Table 1) as well as bibliography screening of relevant reviews on the topic was conducted to minimize the risk of missing reports.
Pre-specified inclusion criteria were: 1) randomized trials of patients receiving DCB versus PB; 2) single-treatment strategy, either DCB or PB, with bailout stenting in case of unsuccessful angioplasty with balloon; 3) treatment of femoropopliteal lesions with critical stenosis (≥70%); and 4) original results published in a peer-reviewed medical journal. Exclusion criteria included: 1) observational studies; 2) treatments other than DCB or PB; 3) use of other treatments in combination with DCB or PB; 4) application of DCB or PB only after stenting (post-dilation); and 5) lesion location in nonfemoropopliteal arterial segment (below-the-knee arteries disease, iliac artery, and so on). Trials including both de novo and restenotic lesions were allowed. Additional information about search and selection methods is reported in the Online Appendix. The risk of bias in each trial was qualitatively assessed as recommended by the Cochrane Collaboration (15).
Primary and secondary outcomes
The primary objective of this meta-analysis was the evaluation of the risk of TLR at 12 months and at long-term follow-up. Secondary outcomes of interest were 12-month and long-term all-cause death.
The analyses of 12-month TLR and 12-month all-cause death were performed by using DerSimonian–Laird random effects models (16,17). Effect size was estimated as risk ratio (RR) and 95% confidence intervals (CIs).
The analyses of long-term TLR and long-term all-cause death were performed by using mixed–effects Poisson regression models with random study effects (18). The analyses used the incident rate of the outcome per patient-years to obtain the pooled incidence rate ratio (IRR) with 95% CI of DCB versus PB (18). IRR was considered the most appropriate outcome for this analysis because it allowed incorporating the different follow-up durations of the included trials. A Bayesian analysis was also performed. Hierarchical models (binomial or Poisson likelihood and logit or log-link function, respectively) with random effects were computed by Markov Chain Monte Carlo method with Gibbs sampling and posterior inference was based on 100,000 simulations following discard of a “burn-in” of 50,000 simulations (19,20). Noninformative priors were used (21) and convergence was graphically appraised according to Gelman–Brooks (22). Posterior inference was expressed as RR or IRR, as appropriate, and the accompanying 95% credible intervals came from the 2.5th and 97.5th centiles of the posterior distribution.
Heterogeneity and publication bias/small study effect
Heterogeneity and publication bias/small study effect assessment are described in the Online Appendix.
Sensitivity and subgroup analyses
Rational and specifications of sensitivity and subgroup analyses are described in the Online Appendix.
Trial sequential analysis
We performed a trial sequential analysis to assess whether cumulative evidence deriving from randomized trials was sufficiently large to declare the superiority of one treatment over the other (23,24). Considering the real distribution of the events in the 2 groups of patients, we anticipated a 25% relative risk reduction (α = 0.05; 1–β = 0.80) in the risk of 12-month TLR by the O’Brien–Fleming α-spending function which allows generating monitoring boundaries accounting for repeated statistical testing. Accordingly, we calculated the required diversity-adjusted information size as number of patients (24).
A total of 8 randomized clinical trials were identified (6–8,25–31) (Online Appendix). Online Figure 1 illustrates the selection process in detail (PRISMA flow diagram). Trial design and methodology are shown in Table 1. Trial inclusion and exclusion criteria are summarized in the Online Table 2. More than one-half of the included trials were not powered to detect differences in TLR and had an angiographic endpoint (late lumen loss) as primary endpoint. The IN.PACT SFA (IN.PACT SFA Clinical Study for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery and/or Proximal Popliteal Artery Using the IN.PACT Admiral™ Drug-Eluting Balloon in a Chinese Patient Population) and LEVANT 2 (A Prospective, Multicenter, Single Blind, Randomized, Controlled Trial Comparing the Moxy Drug Coated Balloon vs. Standard Balloon Angioplasty for Treatment of Femoropopliteal Arteries), the 2 largest trials, were powered for a composite endpoint of major adverse events, including Duplex ultrasonography measurements (Table 1). Within-trial clinical characteristics were comparable and described patients with high cardiovascular risk (Table 2). Superficial femoral artery disease was predominant and variable rates of de novo target lesions, ranging from 0% to 94.9%, were observed (Table 3, Online Table 3). In 3 trials (6,7,25), bailout stenting was significantly more frequent in the PB group and in the 5 remaining trials (8,26–29) was numerically higher (Table 2). Mean lesion length across trials was <10 cm (range: 4.3 to 8.9). Differences in the prevalence of target lesion total occlusion (range: 16.1% to 41.6%) and in the use of predilation were observed across trials (Table 2, Online Table 3). Additionally, in the LEVANT I (A Prospective, Multicenter, Single Blind, Randomized, Controlled Trial Comparing the Lutonix Catheter vs. Standard Balloon Angioplasty for Treatment of Femoropopliteal Arteries With and Without Stenting) trial, a total of 8 DCB malfunctions was recorded (32). All the devices used in these trials released paclitaxel, but there were 4 different DCB catheters (Table 4): 2 trials used the Paccocath (7,26), 3 trials the IN.PACT (8,33,34), 2 trials the Lutonix (6,28), and the remaining trial the Passeo-18 Lux (25). Baseline functional assessment and post-procedural dual antiplatelet therapy duration are reported in the Online Tables 4 and 5.
Qualitative evaluation of the included trials revealed overall moderate risk of bias (Online Figures 2 and 3), which was attributable to incomplete description of random sequence generation and assignment concealment, the infeasibility of operator blinding due to manufacturing differences in devices, the rate of patients lost at angiography and clinical follow-up (8,26,28,29) and possible conflict of interest (26–28,31).
The results of the 12-month TLR analysis are illustrated in the Figure 1. Patients assigned to DCB showed a 67% risk reduction as compared with those receiving PB (RR: 0.33; 95% CI: 0.19 to 0.57). The distribution of the weight of evidence across trials was extremely balanced, but heterogeneity was high (69.4%). Repetition of the analysis in a Bayesian framework confirmed the relevant reduction in the risk of TLR associated with DCB (RR: 0.30; 95% credible interval: 0.14 to 0.58).
Sequential removal of each trial, one at a time, did not significantly alter the results (Online Figure 4): the RR ranged from 0.28 (without LEVANT I or LEVANT 2, the trials in which DCB showed the lowest benefit as compared with PB) to 0.38 (without the IN.PACT SFA, the trial in which DCB showed the greatest benefit as compared with PB) and the summary effect in all cases remained highly significant. Visual inspection of the contour-enhanced funnel plot for 12-month TLR revealed an asymmetric distribution, quantified by “trim and fill” with 4 missing trials to the right of the pooled effects and resulted significant (p = 0.01) at Egger’s linear regression (Online Figure 5).
To analyze the individual impact on heterogeneity, a single trial was removed one at a time, and the individual influence on I2 was estimated (Figure 2). Using this method, we identified 3 trials that amplified the I2: the LEVANT I, IN.PACT SFA, and LEVANT 2 trials (6,27,28). This was also graphically appraisable by Baujat plot (Figure 2, left panel). Subsequently, because the global I2 remained high, we investigated the possible combinations of trials, which resulted in an I2 value below the threshold of low heterogeneity (<25%). Only by removing the combination of the LEVANT I and LEVANT 2 trials was heterogeneity nonsignificant, suggesting that this cluster introduced relevant differences in terms of 12-month TLR.
Stratifying the trials according to the type of DCB used (Figure 3, Table 4), we observed a similar effect in the trials using the IN.PACT and Paccocath DCBs, while the trials using the Lutonix DCB were associated with a less marked, nonsignificant treatment effect favoring DCB (RR: 0.79; 95% CI: 0.53 to 1.14). The Passeo–18 Lux DCB catheter was used only in a single small trial and, although effect size was comparable with the IN.PACT and Paccocath DCBs, significance was borderline (RR: 0.38; 95% CI: 0.14 to 1.06). Within-group heterogeneity was not detected, although this may be likely due to the limited number of trials. The pooled effect after exclusion of the 2 trials using the Lutonix DCB (6,28) showed a higher risk reduction (RR: 0.21; 95% CI: 0.14 to 0.32) compared with main analysis results (Online Figure 6).
The varying prevalence of de novo stenotic lesions was explored by grouping the trials according to median trial-level proportion (≤71.3% or >71.3%) (Figure 4). Results in the 2 groups remained consistent with the main analysis. Finally, although the FAIR (Randomized Femoral Artery In–Stent Restenosis) trial significantly differs from the others, enrolling only patients with in-stent restenotic lesions, its removal did not change the superiority of DCB over PB (RR: 0.35; 95% CI: 0.20 to 0.63) and the point estimate after exclusion was similar to main analysis pooled value.
The impact of prevalence of target lesion total occlusion at baseline was explored by grouping trials according to rate ≤27.6% or >27.6% (Online Figure 7). The cutoff rate was extracted by the median rate of target lesion total occlusion across the included trials. The subgroup analysis confirmed the results of main analysis.
The additional primary endpoint of long-term TLR (Figure 5, left panel) was assessed by using the maximum trial-level available follow-up (mean follow-up time: 1.9 years; range: 1-5) for a total of 1,843 patient-years. The meta-analysis of long-term TLR confirmed that the superior effectiveness of DCB over PB was stable over time (IRR 0.35; 95% CI: 0.24 to 0.51). Heterogeneity was moderate (I2 = 44.2%) and also in this case mainly due to the LEVANT I and LEVANT 2 trials (6,28), which showed a nonsignificant effect moderately favoring DCB. After excluding these 2 trials, heterogeneity was no longer detected and the summary estimate favoring DCB seemed to be magnified compared with main analysis (Online Figure 8). The analyses were repeated using a Bayesian framework with concordant results.
Results of the meta-analysis for the secondary endpoints of 12-month all-cause death are illustrated in the Online Figure 9: the pooled risk of all-cause death at 12 months was similar between the 2 treatments (RR: 0.96; 95% CI: 0.47 to 1.95). No significant asymmetry was visualized in the contour-enhanced funnel plot for 12-month all-cause death and Egger’s test was nonsignificant (Online Figure 10). After performing a meta-analysis for the long-term all-cause death outcome (Figure 5, right panel), summary IRR did not favor one treatment over the other (IRR: 1.13; 95% CI: 0.60 to 2.15). An excess of mortality with DCB was observed in 1 study, the IN.PACT SFA trial. Bayesian analysis was consistent with frequentist estimate. Other major adverse events were overall extremely rare and comparable in the 2 groups, although functional benefits at follow-up were less evident than TLR reduction (Online Table 6).
Trial sequential analysis showed that the number of available trials is likely sufficient to demonstrate overall superior 12-month antirestenotic efficacy of DCB over PB (Figure 6). Indeed, after sequential addition of trials according to a chronological order (Z-score), very early the cumulative evidence reached not only the conventional boundary (standard estimate of required evidence), but also the α-spending function monitoring boundary (adjusted estimate of required evidence). The analysis predicted that a total of 421 patients was required to gain sufficient statistical power and adjusting the CI of the main analysis for repeated statistical testing the summary effect remained highly significant (adjusted 95% CI: 0.15 to 0.69).
In this meta-analysis, we observed 5 key findings: 1) DCB is significantly superior to PB in reducing the risk of TLR at 12 months in patients with femoropopliteal artery disease and this benefit appears to persist over time with reduced rates of TLR at long-term follow-up; 2) the antirestenotic benefits of DCB are consistent across subsets of either de novo or restenotic lesions; 3) there was some evidence of differential efficacy of available paclitaxel DCBs; 4) there was no difference in terms of mortality between treatment with DCB or PB; and 5) additional randomized clinical trials comparing currently available DCB with PB in a general clinical and angiographic subset do not seem to be required.
Our meta-analysis differs from prior meta-analyses (10–12) in several aspects: 1) it is updated to include recently published randomized trials; 2) we focus on clinical outcome measures, such as TLR and all-cause death, both at 12 months and in the long term; 3) it systematically assesses and explores reasons for observed heterogeneity in trial-level results; and 4) it provides novel insights regarding the available evidence on DCB versus PB using trial sequential analysis.
This meta-analysis provides evidence of clear superiority of DCB over PB for the treatment of femoropopliteal artery disease, in terms both of 12-month and long-term TLR. Indeed, the durability of DCB therapy superiority is particularly noteworthy. Concerns had been raised that the lower late lumen loss and binary restenosis observed at 6 months in patients with lower limb disease treated with DCB enrolled in trials with planned angiographic surveillance may not persist over the longer term. Our analysis, however, shows that DCB therapy continues to be associated with a reduced risk of TLR at a mean follow-up of 1.9 years. This finding is also in agreement with the recently available long-term follow-up of trials comparing DCB with PB in the treatment of coronary in-stent restenosis (32,33). The cumulative incidence of TLR in the PB group was slightly higher than recently reported (4,34). This may have exaggerated the magnitude of the results favoring DCB but the margin of significance of summary effect was clear.
The observed heterogeneity between trials seemed to be explained by the inclusion of the 2 trials using the Lutonix DCB (6,28). Indeed, heterogeneity was not detected by excluding the trials using the Lutonix DCB and using an influence analysis we showed that the LEVANT I and LEVANT 2 trials majorly contributed to I2 increase. The different effectiveness of the DCB treatment in the 2 trials using the Lutonix DCB has 2 possible explanations: on the one hand, this result may suggest a lower efficacy of this type of DCB compared with the others; in contrast, the findings may reflect trial design characteristics specific to LEVANT I and LEVANT 2 trials. This interpretation of the heterogeneity is graphically expressed by the strong asymmetry of the funnel plot, with the LEVANT I and LEVANT 2 trials falling in the nonsignificance area. However, the different results of these 2 trials may have introduced only heterogeneity without implying a publication bias (“true” heterogeneity) and the 4 missing trials to the right of mean effect required to make symmetric the funnel plot were corresponding to the high-significance area (p < 0.01), which is not associated generally with the presence of a small study effect (35).
Another important finding of this meta-analysis is the possible differential effectiveness observed among DCBs. This finding is in agreement with the heterogeneity analyses, providing a reasonable clinical explanation. Indeed, the attenuated antirestenotic effects associated with the trials using the Lutonix DCB could be explained by the lower paclitaxel dose density compared with the other DCBs (2 vs. ≥3 μg/mm2). In the animal model, DCB effectiveness appeared at the dose of 1 μg/mm2 with an incremental antirestenotic effect up to 3 μg/mm2, but beyond this value neointimal area remained comparable (36). However, paclitaxel dose density is only one of the factors influencing DCB efficacy. Indeed, excipients are key components of the balloon coating and regulate paclitaxel elution (37). The Lutonix DCB coating drug carrier consists of polysorbate and sorbitol, which have not been extensively explored in animal models and may have different effectiveness compared with excipients of the other DCBs (6,10,28,38).
Despite the clear reduction in TLR associated with DCB, there was no difference in terms of mortality between DCB treatment and PB. This finding remained unchanged after comparing incidence rate of all-cause death in the 2 groups at longest available follow-up.
We did not meta-analyze other secondary clinical outcomes because the qualitative review of data showed incomplete reporting (i.e., primary patency) and extremely rare occurrence (i.e., major amputation, thrombosis, and myocardial infarction). Nevertheless, data review indicated some interesting findings. Indeed, with the exception of the FAIR trial, the number of target lesion thrombosis in patients treated with DCB was in all trials equal to or lower than PB group, suggesting that concerns about a potential DCB thrombogenic tendency compared with PB could not be supported. Moreover, periprocedural dissections were comparable between both treatment groups though large differences among trials were observed.
Finally, we also performed a trial sequential analysis with the aim to assess the requirement for further studies investigating the comparative efficacy of DCB versus PB in the treatment of femoropopliteal artery disease. Our findings indicate that evidence of superiority of currently available DCBs is clear and suggests that future investigations should be oriented to comparisons between DCB and underexplored promising devices for femoropopliteal artery disease treatment, such as drug-eluting stents, or specific common high-risk clinical and angiographic subsets, such as diabetes, long lesion, in-stent restenosis, and total occlusion. However, although general proprieties of the IN.PACT, Paccocath and Lutonix DCBs seem to be well-evaluated, further evidence with Passeo–18 Lux is required.
As with any meta-analysis, our report shares the limitations of the original trials and potential sources of heterogeneity in clinical and procedural characteristics cannot be fully explored without individual patient data. Metaregression can only partially overcome the absence of individual patient data and given the strong dependence on the numbers of trials was not performed (39).
More specifically, the results of our meta-analysis should be interpreted taking the following limitations into account. First, 2 of the included trials (Biolux P–I and FemPac [Paclitaxel Coated Balloon Catheter for Inhibition of Restenosis in Femoropopliteal Arteries]) included minimal rates (n = 12) of target lesion involving below-the-knee arteries (25,26). Additionally, the analyses of 12-month TLR and all-cause death include 6-month data for the FemPac trial, because events at 12 months were not provided (26). Moreover, the third arm of the THUNDER (Local Taxan With Short Time Contact for Reduction of Restenosis in Distal Arteries) trial (paclitaxel in contrast media) was not pooled, implying a remote possibility that benefits of randomization could have been lost (7). Second, in the LEVANT I trial a 1:1 randomization was done following stratification according to flow limiting dissection or ≥70% resistant stenosis after initial treatment and, although DCB or PB assignment was random, 25% of patients (namely “stent group”) received provisional stenting (28). Third, we detected significant differences between trials using the Lutonix DCB and those using the other catheters. However, no randomized clinical trials directly compared the different devices and the difference observed could be due to confounding factors. Fourth, only 50% of trials reported a clinical follow-up between 24 and 60 months and the mean follow-up in this meta-analysis was of 1.9 months. Although the methodology used attempted to account for these issues, it cannot replace time-to-event analyses with individual patient data and uniform long-term follow-up. Fifth, the significant funnel plot asymmetry in relation to TLR was considered likely to be representative of “true” heterogeneity deriving from the different catheter types within DCB group rather than a small study effect. However, due to the limited number of trials, this question cannot be completely answered. Finally, the paucity of major adverse events and the significant variations in reporting functional variations of lower limb revascularization with DCB and PB across the trials did not allow the meta-analysis of these outcomes. Functional benefits at follow-up of femoropopliteal revascularization with DCB over PB were less evident than antirestenotic effects. Future trials with DCB should specifically address very late clinical and functional improvements.
The treatment of femoropopliteal artery disease with DCB significantly reduces the risk of 12-month TLR compared with PB without any effect on all-cause mortality. The observed treatment effect persists at long-term follow-up. Results were consistent across subsets of included lesions, but trials using the Lutonix DCB introduced significant heterogeneity, suggesting an attenuated antirestenotic effect. Additional trials to confirm the superior antirestenotic efficacy of currently available DCBs versus PB angioplasty in a general clinical and angiographic subset of patients with femoropopliteal artery disease are not required. Future trials should focus on the comparison between DCB and potentially more effective comparators such as drug-eluting stents.
WHAT IS KNOWN? In randomized clinical trials, DCBs are generally associated with superior antirestenotic efficacy compared with plain balloon. However, these trials are powered only for surrogate endpoints or composite endpoints, including clinical and surrogate parameters. The clinical impact of femoropopliteal artery revascularization with DCB is variable across reports and not explored in an adequately large number of patients. Moreover, the influence of target lesion type and the long-term durability of DCB effects are poorly defined. Finally, no randomized trials directly comparing the different available DCB devices have been conducted.
WHAT IS NEW? In patients undergoing femoropopliteal artery intervention, DCB therapy should be preferred over conventional plain balloon angioplasty due to superior antirestenotic effectiveness in terms of TLR. At long-term follow-up, the lower incidence of TLR associated with DCB seems to be durable. Although DCB performance seems not influenced by target lesion type, differential effectiveness across currently available devices was detected. Survival is not influenced by the revascularization strategy.
WHAT IS NEXT? Differences between the 2 treatments in terms of symptoms and functional improvement are not delineated sufficiently in randomized clinical trials and the specific subgroups of patients which might receive greatest benefit from revascularization with DCB is not defined. Future trials on DCB should potentially include more effective comparators such as drug-eluting stents.
For supplemental methods as well as tables and figures, please see the online version of this article.
Dr. Giacoppo has been awarded with a grant from the EAPCI (European Association Percutaneous Coronary Intervention). Dr. Kastrati has reported submission of patent applications in relation to drug-eluting stent technology. Dr. Byrne has received lecture fees from B. Braun Melsungen AG, Biotronik and Boston Scientific; and institutional research grants from Boston Scientific and Heartflow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- confidence interval
- drug-coated balloon
- incidence rate ratio
- plain balloon
- Preferred Reporting Items for Systematic Reviews and Meta-Analyses
- risk ratio
- target lesion revascularization
- Received April 19, 2016.
- Revision received May 26, 2016.
- Accepted June 2, 2016.
- American College of Cardiology Foundation
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