PReventing Amputations using Drug eluting StEnts - PaRADISE

Description:

Chronic limb ischemia (CLI) is a common source of mortality and morbidity in patients with peripheral vascular disease. Although bypass surgery is preferred to percutaneous transluminal angioplasty (PTA), it is often inadequate. The current trial sought to compare outcomes between patients undergoing below-the-knee (BTK) drug-eluting stent (DES) implantation for CLI, versus historic controls from the Trans-Atlantic Inter-Society Consensus (TASC) II document and the Bypass Versus Angioplasty in Severe Ischemia of the Leg (BASIL) trial.

Hypothesis:

Amputation-free survival with BTK DES would be superior to that noted in the BASIL trial.

Study Design

  • Parallel

Patients Screened: 118
Patients Enrolled: 106
Mean Follow Up: 3 years
Mean Patient Age: 74 years
Female: 34

Patient Populations:

  • Presence of CLI
  • Able to cross BTK lesion with 0.014” wire

Primary Endpoints:

  • Major amputation
  • All-cause mortality
  • Tissue healing
  • Relief of rest pain

Secondary Endpoints:

  • Major adverse events

Drug/Procedures Used:

Patients were enrolled when the 0.014” wire crossed the targeted BTK lesion. Lesions were predilated to test lesion compliance, and stents were deployed to achieve a slight negative residual compared to the distal reference vessel. A goal of two DES per limb was sought.

Concomitant Medications:

Before intervention, all patients were started on a regimen of aspirin 81 mg, clopidogrel 75 mg daily, or ticlopidine 250 mg bid. Patients received unfractionated heparin, 40-50 U/kg. After the procedure, indefinite thienopyridine, aspirin, and lipid therapy was encouraged.

Principal Findings:

Of 118 patients in whom an intervention was attempted, 12 patients were excluded due to inability to cross total occlusions. A total of 106 patients (118 limbs) were thus enrolled. The mean creatinine was about 1.5 mg/dl, and about 3.5% of the patients were on dialysis. Lesions were evenly distributed between Rutherford-Becker categories 4 (38%), 5(31%), and 6 (31%).

The contralateral retrograde approach was used 92% of the time. Contemporaneous superficial femoral artery (SFA) or popliteal artery interventions were performed in 48% of limbs. Occlusion of all three tibial vessels or jeopardized single-vessel run-off was noted in 74% of patients. Technical success in delivering stents was 100%, while angiographic success was 96%. The majority of stents used were sirolimus-eluting (83%). The mean number of stents per limb was 1.9, with a median diameter of the stents being 3 mm.

Wound healing and relief of resting pain were demonstrated in 93% of patients. There was only one major adverse event (stroke/myocardial infarction/infection/compartment syndrome/dissection/distal embolization/vessel occlusion/RP bleed/pseudoaneurysm/hematomas/contrast nephropathy) in the periprocedural period. The cumulative incidence of major amputations at 1 year was 5.1%, and at 3 years was 6%. Rutherford category 6 patients tended to have a trend toward worse survival, as compared with category 4 and 5 patients.

Amputation-free survival was better with BTK DES when compared with historical controls from the BASIL PTA arm at 1 year (5.1% vs. 10.9%, p = 0.03), and at 3 years (6% vs. 15.9%, p = 0.03). When compared with the BASIL surgical arm, results were better at 1 year (5.1% vs. 13.9%, p = 0.01), but not at 3 years (6% vs. 10.9%, p = 0.12). Overall survival was similar, as compared with both the BASIL PTA (p = 0.22) and surgical arms (p = 0.41) at 3 years.

Repeat angiographic evaluation was necessary in 35.8% of the patients, either due to recurrent ipsilateral symptoms, or for asymptomatic patients undergoing angiography for other vascular procedures. Of the symptomatic patients, stent failure was noted in 24%. Overall stent failure seemed to be less with sirolimus-eluting, as compared with paclitaxel-eluting stents.

Interpretation:

The results of this trial indicate that DES BTK is safe and effective in patients with CLI, who are at high risk for needing limb amputations. These rates seem to be higher than those noted historically from the PTA arm, and equal to the surgical arm of the BASIL study, at 3 years.

The limitations of this trial are that this was a single-center study, and there were no contemporary controls. Future multicenter trials comparing BTK DES with bypass surgery are necessary.

References:

Feiring AJ, Krahn M, Nelson L, Wesolowski A, Eastwood D, Szabo A. Preventing Leg Amputations in Critical Limb Ischemia With Below-the-Knee Drug-Eluting Stents: The PaRADISE (PReventing Amputations using Drug eluting StEnts) Trial. J Am Coll Cardiol 2010;55:1580-1589.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Interventions and Vascular Medicine, Chronic Angina

Keywords: Aneurysm, False, Myocardial Infarction, Stroke, Coronary Restenosis, Drug-Eluting Stents, Femoral Artery, Creatinine, Sirolimus, Pain, Hematoma, Angioplasty, Balloon, Coronary, Peripheral Vascular Diseases, Paclitaxel, Renal Dialysis, Compartment Syndromes, Wound Healing, Popliteal Artery


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