Antithrombotic Treatment for Peripheral Arterial Occlusive Disease.

BACKGROUND: Patients with peripheral arterial occlusive disease (PAOD) are at ele - vated risk for cardiovascular events and vascular events affecting the limbs. The goals of antithrombotic treatment are to keep vessels open after revascularization, to prevent cardiovascular events, and to lessen the frequency of peripheral ischemia and of amputation. METHODS: This review is based on pertinent publications retrieved by a selective literature search, with particular attention to meta-analyses, randomized controlled trials, and the German and European angiological guidelines. RESULTS: Diabetes mellitus and nicotine abuse are the main risk factors for lower limb PAOD. The evidence for the efficacy and safety of antithrombotic treatment in patients with PAOD is limited, in particular, after surgical or endovascular revascularization. Intensifying antithrombotic treatment with stronger antiplatelet therapy (APT), dual antiplatelet therapy (DAPT), or antiplatelet therapy combined with anticoagulation lowers the rate of peripheral revascularization (relative risk [RR] 0.89; 95% confidence interval [0.83; 0.94]), amputation (RR 0.63; [0.46; 0.86]), and stroke (RR 0.82; [0.70; 0.97]) but raises the risk of bleeding (RR 1.23; [1.04; 1.44]). Pre - dictors for peripheral vascular events include critical limb ischemia and having previously undergone a revascularization procedure or an amputation. CONCLUSION: Antiplatelet therapy should only be intensified for a limited time, or if the risk of ischemia is high. Before and during intensified antiplatelet therapy, the risk of bleeding should be assessed and weighed against the risk of ischemia. No validated score is available to estimate the risk of hemorrhagic complications in patients with PAOD. New antithrombotic therapies should not be used indiscriminately, but should rather be reserved for selected groups of patients.

[Dual Pathway Inhibition in Atherosclerosis - Which Patients Benefit?] / Dual-Pathway-Inhibition bei Atherosklerose ­ wer profitiert?

Dual antithrombotic therapy (DAT) with low-dose rivaroxaban in combination with acetylsalicylic acid (ASA) is available to patients with stable atherosclerotic disease as a new therapeutic option.The results of the COMPASS trial demonstrate a significant relative risk reduction of cardiovascular outcomes by 24 % with low-dose DAT in patients with stable peripheral arterial disease or coronary heart disease.Despite a guideline adherent secondary prevention therapy, the cardiovascular event rate with ASA alone during the mean study period of almost two years was 5.4 %. The absolute reduction of the event rate by the low-dose DAT is low at 1.3 %. Consequently, it is important to identify groups of patients at high risk for cardiovascular events. These patients are particularly qualified to receive a DAT regimen and can be characterized using high-risk features.The individual ischemic risk profile may be further defined by the presence of polyvascular atherosclerosis, concomitant diseases, and ischemic events in the past. The quo ad vitam reduced prognosis of patients with polyvascular atherosclerosis advocates a polyvascular screening, even in supposedly stable patients with coronary heart disease and peripheral arterial disease.An intensification of antithrombotic therapy is naturally associated with an increased risk of bleeding. Therefore, the risk-reduction of ischemic events should be weighed individually against the risk of bleeding.A low-dose DAT is particularly suitable for patients with a high ischemic risk and a low risk of bleeding.

Promising role of drug-coated balloons in the tibial vessels?

In order to assess the role of drug-coated balloons (DCB) in below-the-knee (BTK) artery interventions, we analyzed randomized trials which compare coated to non-coated balloons and additionally a direct comparison of drug-eluting stents (DES) with DCB. As angioplasty with non-coated balloons is per guideline-recommendation still standard of care for below-the-knee artery endovascular treatment, we focused on the direct comparison of efficacy and clinical outcome data of both treatment modalities. Data from peer reviewed and published trials were consulted. For each single study, primary and secondary endpoints were reported and compared. Three single-center, non-core lab adjudicated trials showed encouraging data which suggests that DCB in BTK arteries effectively inhibit the risk of early restenosis, but the pivotal, prospectively randomized, multicenter, core lab adjudicated trials failed to match with these result. Limitations of DEB treatment and trials in BTK arteries had been reported, hence a technical evaluation of possible side effects of DCB treatment and of trial design was taken into account. On the basis of the results available, the distinguishing findings of drug eluting effects in the femoropopliteal region cannot be transferred to BTK arteries. Refinement of the existing DCB technology and of future trial design should be considered. To adjudicate on DCB technology applied for BTK treatment is premature and it is mandatory to be kept under evaluation, because the potential benefit, with respect to the compelling results in the femoropoliteal arteries, could be huge to improve endovascular BTK and especially CLI treatment.

Promising role of drug-coated balloons in the tibial vessels?

To judge on the role of drug-coated balloons (DCB) in below-the-knee (BTK) artery interventions, we analyzed randomized trials which compare coated to non-coated balloons and additionally a direct comparison of drug-eluting stents (DES) with DCB. As angioplasty with non-coated balloons is per guideline-recommendation still standard of care for below- the-knee artery endovascular treatment, we focused on the direct comparison of efficacy and clinical outcome data of both treatment modalities. Data from peer reviewed and published trials were consulted. For each single study, primary and secondary endpoints were reported and compared. Three single-center, non-core lab adjudicated trials showed encouraging data which suggests that DCB in BTK arteries effectively inhibit the risk of early restenosis, but the pivotal, prospectively randomized, multicenter, core lab adjudicated trials failed to match with these result. Limitations of DEB treatment and trials in BTK arteries had been reported, hence a technical evaluation of possible side effects of DCB treatment and of trial design was taken into account. On the basis of the results available, the distinguishing findings of drug eluting effects in the femoropopliteal region cannot be transferred to BTK arteries. Refinement of the existing DCB technology and of future trial design should be considered. To adjudicate on DCB technology applied for BTK treatment is premature and it is mandatory to be kept under evaluation, because the potential benefit, with respect to the compelling results in the femoropoliteal arteries, could be huge to improve endovascular BTK and especially CLI treatment.

Paclitaxel-coated balloons reduce restenosis after femoro-popliteal angioplasty: evidence from the randomized PACIFIER trial.

BACKGROUND: Peripheral percutaneous transluminal angioplasty is fraught with a substantial risk of restenosis and reintervention. A drug-eluting balloon (DEB) based on a novel coating was compared with uncoated balloons in patients undergoing femoro-popliteal percutaneous transluminal angioplasty. METHODS AND RESULTS: Patients with symptomatic femoro-popliteal atherosclerotic disease undergoing percutaneous transluminal angioplasty were randomized to paclitaxel-coated IN.PACT Pacific or uncoated Pacific balloons. The primary end point was late lumen loss at 6 months assessed by blinded angiographic corelab quantitative analyses. Secondary end points were binary restenosis and Rutherford class change at 6 months, and target lesion revascularization plus major adverse clinical events (major adverse events=death, target limb amputation, or target lesion revascularization) at 6 and 12 months. Eighty-five patients (91 cases=interventional procedures) were randomized in 3 hospitals (44 to DEB and 47 to uncoated balloons). Average lesion length was 7.0 ± 5.3 and 6.6 ± 5.5 cm for DEB and control arm, respectively. Procedural success was obtained in all cases. Six-month quantitative angiography showed that DEB were associated with significantly lower late lumen loss (-0.01 mm [95% CI, -0.29; 0.26] versus 0.65 mm [0.37; 0.93], P=0.001) and fewer binary restenoses (3 [8.6%] versus 11 [32.4%], P=0.01). This translated into a clinically relevant benefit with significantly fewer major adverse events for DEB versus uncoated balloons up to 12 months (3 [7.1%] versus 15 [34.9%], P<0.01) as well as target lesion revascularizations (3 [7.1%] versus 12 [27.9%], P=0.02). CONCLUSIONS: Use of IN.PACT Pacific DEB is associated with significant reductions in late lumen loss and restenoses at 6 months, and reinterventions after femoro-popliteal percutaneous transluminal angioplasty up to 1 year of follow-up. CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Unique identifier: NCT01083030.