Sirolimus vs Paclitaxel: Chronic vascular effects through DCB treatment in symptomatic peripheral artery disease

Medina Sacirovic (Essen)1, D. Messiha (Essen)1, S. Fakea (Essen)1, B. Akan (Essen)1, T. Rassaf (Essen)1, C. Rammos (Essen)1

1Universitätsklinikum Essen Klinik für Kardiologie und Angiologie Essen, Deutschland

 

BACKGROUND

Peripheral artery disease (PAD) is characterized by plaque formation, chronic inflammation
of the vessels and endothelial dysfunction.

The impairment of the endothelial function does not only initiate but further provokes the
development and progression of atherosclerosis and cardiovascular diseases, resulting in an
increased risk of adverse limb events, cardio- and cerebrovascular events, making efficient
lesion management crucial.

Sirolimus-coated balloons (SCB) represent a promising alternative drug eluting device to the
already existing paclitaxel coated balloon (PCB) for the treatment of PAD.

Drug eluting device treatment alters the endothelium but the impact is only incompletely understood.

We have now determined the impact and mechanisms of Sirolimus and Paclitaxel on

endothelial function in symptomatic PAD.

 

PATIENTS, MATERIALS AND METHODS

In this investigator-initiated randomized controlled trial 70 patients with PAD undergoing

peripheral vascular intervention were recruited. These patients exhibited complex

femoropopliteal artery lesions and chronic symptomatic lower limb ischemia (Rutherford 2-5).

The study population was randomized, resulting in 36 patients (67,6±9,9 years, 69% men)

being treated with SCB (Sirolimus Selution SLR™, MedAlliance) and 34 patients (67,4±8,9

years, 68% men) with PCB (Paclitaxel In.Pact™, Medtronic) angioplasty.

The primary outcome was the change in endothelial function as determined through flow-

mediated dilation (FMD) in the proximal non-stenotic segment of the targeted superficial

femoral artery (SFA), non-target SFA as well as the brachial artery.

Secondary endpoints included vascular stiffness as determined by pulse wave velocity, along

with analysis of peripheral perfusion through evaluation of the Ankle-Brachial-Index to

objectify vascular function.

Additionally, biochemical markers of vascular function were assessed including inflammation

markers (hs-CRP, IL-6, TGF-ß), and endothelial function markers (Endothelin-1). All clinical

outcomes were assessed prior and one and six 12 months after intervention.

 

RESULTS

70 patients enrolled completed their six-months clinical follow-up, leaving us with current

data on the chronic impact after DCB treatment. Patients treated with Sirolimus showed a

sustained improvement in endothelial function after six months (FMD target 3,3±0,6% to

4,7±0,4%; p<0,05), which was corroborated in the Paclitaxel group (FMD target 3,6±0,6% to

4,5±0,7%; p<0,05). Comparing the improvement in endothelial function after six months, a

greater improvement was evident in the SCB group as compared to PTX treatement (ΔFMD

PCB +0,82% vs SCB +1,22%, p<0,05).
This was corroborated by reduced markers of inflammation.

 

CONCLUSION

Evidence is provided for an improved local and systemic endothelial function after

interventional drug eluting balloon treatment of PAD. This improvement is sustained

throughout a six months follow-up, making further improvement of the systemic endothelial

function evident.

Our data will support the concept for a better mechanistic understanding to enhance

endovascular treatment strategies in PAD.

 
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