@article {30595,
	title = {Editor{\textquoteright}s choice - risk of major amputation following application of      paclitaxel coated balloons in the lower limb arteries: A systematic review
      and meta-analysis of randomised controlled trials
},
	journal = {Eur. J. Vasc. Endovasc. Surg.},
	volume = {63},
	year = {2022},
	month = {2022},
	pages = {60-71},
	publisher = {Elsevier BV},
	abstract = {OBJECTIVE: There have been concerns about the long term safety of      paclitaxel coated devices in the lower limbs. A formal systematic review
      and meta-analysis of randomised controlled trials (RCTs) was performed to
      examine the long term risk of major amputation using paclitaxel coated
      balloons in peripheral arterial disease (PAD). METHOD: This systematic
      review was registered with PROSPERO (ID 227761). A broad bibliographic
      search was performed for RCTs investigating paclitaxel coated balloons in
      the peripheral arteries (femoropopliteal and infrapopliteal) for treatment
      of intermittent claudication or critical limb ischaemia (CLI). The
      literature search was last updated on 20 February 2021 without any
      restrictions on publication language, date, or status. Major amputations
      were analysed with time to event methods employing one and two stage
      models. Sensitivity and subgroup analyses, combinatorial meta-analysis,
      and a multivariable dose response meta-analysis to examine presence of a
      biological gradient were also performed. RESULTS: In all, 21 RCTs with 3
      760 lower limbs were analysed (52\% intermittent claudication and 48\% CLI;
      median follow up two years). There were 87 major amputations of 2 216
      limbs in the paclitaxel arms (4.0\% crude risk) compared with 41 major
      amputations in 1 544 limbs in the control arms (2.7\% crude risk). The risk
      of major amputation was significantly higher for paclitaxel coated
      balloons with a hazard ratio (HR) of 1.66 (95\% CI 1.14 - 2.42; p = .008,
      one stage stratified Cox model). The prediction interval was 95\% CI 1.10 -
      2.46 (two stage model). The observed amputation risk was consistent for
      both femoropopliteal (p = .055) and infrapopliteal (p = .055) vessels.
      Number needed to harm was 35 for CLI. There was good evidence of a
      significant non-linear dose response relationship with accelerated risk
      per cumulative paclitaxel dose (chi square model p = .007). There was no
      evidence of publication bias (p = .80) and no significant statistical
      heterogeneity between studies (I2 = 0\%, p = .77). Results were stable
      across sensitivity analyses (different models and subgroups based on
      anatomy and clinical indication and excluding unpublished trials). There
      were no influential single trials. Level of certainty in evidence was
      downrated from high to moderate because of sparse events in some studies.
      CONCLUSION: There appears to be heightened risk of major amputation after
      use of paclitaxel coated balloons in the peripheral arteries. Further
      investigations are warranted urgently.
},
	keywords = {Amputation, Balloon, Dose, Meta-analysis, Paclitaxel-coated, Randomised},
	isbn = {1078-5884},
	url = {http://dx.doi.org/10.1016/j.ejvs.2021.05.027https://www.ncbi.nlm.nih.gov/pubmed/34326002},
	author = {Katsanos, Konstantinos and Spiliopoulos, Stavros and Teichgr{\"a}ber, Ulf and Kitrou, Panagiotis and Del Giudice, Costantino and Bj{\"o}rkman, Patrick and Bisdas, Theodosios and de Boer, Sanne and Krokidis, Miltiadis and Karnabatidis, Dimitrios}
}
