Τίτλος:
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
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 (I-2 = 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anatomy and clinical indication and excluding unpublished trials).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.
Συγγραφείς:
Katsanos, Konstantinos
Spiliopoulos, Stavros
Teichgraeber, Ulf
and Kitrou, Panagiotis
Del Giudice, Costantino
Bjoerkman,
Patrick
Bisdas, Theodosios
de Boer, Sanne
Krokidis,
Miltiadis
Karnabatidis, Dimitrios
Περιοδικό:
European Journal of Vascular and Endovascular Surgery
Εκδότης:
W B SAUNDERS CO LTD
Λέξεις-κλειδιά:
Amputation; Balloon; Dose; Meta-analysis; Paclitaxel-coated; Randomised
DOI:
10.1016/j.ejvs.2021.05.027
