SWITCH: A Randomised, Sequential, Open-label Study to Evaluate the Efficacy and Safety of Sorafenib-sunitinib Versus Sunitinib-sorafenib in the Treatment of Metastatic Renal Cell Cancer.

BACKGROUND: Understanding how to sequence targeted therapies for metastatic renal cell carcinoma (mRCC) is important for maximisation of clinical benefit. OBJECTIVES: To prospectively evaluate sequential use of the multikinase inhibitors sorafenib followed by sunitinib (So-Su) versus sunitinib followed by sorafenib (Su-So) in patients with mRCC. DESIGN, SETTING, AND PARTICIPANTS: The multicentre, randomised, open-label, phase 3 SWITCH study assessed So-Su versus Su-So in patients with mRCC without prior systemic therapy, and stratified by Memorial Sloan Kettering Cancer Center risk score (favourable or intermediate). INTERVENTION: Patients were randomised to sorafenib 400mg twice daily followed, on progression or intolerable toxicity, by sunitinib 50mg once daily (4 wk on, 2 wk off) (So-Su), or vice versa (Su-So). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was improvement in progression-free survival (PFS) with So-Su versus Su-So, assessed from randomisation to progression or death during second-line therapy. Secondary endpoints included overall survival (OS) and safety. RESULTS AND LIMITATIONS: In total, 365 patients were randomised (So-Su, n=182; Su-So, n=183). There was no significant difference in total PFS between So-Su and Su-So (median 12.5 vs 14.9 mo; hazard ratio [HR] 1.01; 90% confidence interval [CI] 0.81-1.27; p=0.5 for superiority). OS was similar for So-Su and Su-So (median 31.5 and 30.2 mo; HR 1.00, 90% CI 0.77-1.30; p=0.5 for superiority). More So-Su patients than Su-So patients reached protocol-defined second-line therapy (57% vs 42%). Overall, adverse event rates were generally similar between the treatment arms. The most frequent any-grade treatment-emergent first-line adverse events were diarrhoea (54%) and hand-foot skin reaction (39%) for sorafenib; and diarrhoea (40%) and fatigue (40%) for sunitinib. CONCLUSIONS: Total PFS was not superior with So-Su versus Su-So. These results demonstrate that sorafenib followed by sunitinib and vice versa provide similar clinical benefit in mRCC. PATIENT SUMMARY: We investigated if total progression-free survival (PFS) is improved in patients with advanced/metastatic kidney cancer who are treated with sorafenib and then with sunitinib (So-Su), compared with sunitinib and then sorafenib (Su-So). We found that total PFS was not improved with So-Su compared with Su-So, but both treatment options were similarly effective in patients with advanced/metastatic kidney cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00732914, www.clinicaltrials.gov.

Results after balloon angioplasty or stenting of atherosclerotic subclavian artery obstruction.

INTRODUCTION: Endovascular therapy is an accepted treatment strategy in occlusive disease of the subclavian artery. The purpose of this study was to evaluate the technical and clinical long-term outcome following either balloon angioplasty (plain balloon angioplasty (PTA)) or stenting. PATIENTS AND METHODS: The authors retrospectively analyzed 108 interventions of atherosclerotic lesions of subclavian arteries or the brachiocephalic trunk (107 patients; mean age of 66 +/- 9 years; 90% symptomatic) representing 92% of the patients treated with subclavian artery obstructive disease during a 10-year period. Primary endpoint of the study was the 1-year primary patency rate. Follow-up was based on oscillometry, Doppler blood pressure measurements, and duplex ultrasound. RESULTS: The primary success rate was 97% (100% for stenoses (78/78) and 87% for total occlusions (26/30)). Treatment modalities included PTA alone (13%; n = 14) or stenting (87%; n = 90) with balloon-expandable (n = 61), self-expanding (n = 17), or both types of devices (n = 12). The 1-year primary patency rate of the 97 patients eligible for follow-up was 88%, for the subgroups 79% (PTA) and 89% (stenting; P = 0.2). The blood pressure difference between both limbs at baseline was 45 +/- 26 mm Hg and dropped to 10 +/- 14 mm Hg (P < 0.001) after the intervention and 15 +/- 19 mm Hg at 1 year (P < 0.01). CONCLUSION: Endovascular therapy of atherosclerotic subclavian artery obstructions result in excellent acute success rates even in total occlusions. Results evince good durability of endovascular therapy for atherosclerotic occlusive disease of subclavian arteries and with a trend towards better outcome with stenting compared to PTA.

Acute and long-term outcome of endovascular therapy for aortoiliac occlusive lesions stratified according to the TASC classification: a single-center experience.

PURPOSE: To compare acute and long-term outcomes of endovascular therapy for TASC (TransAtlantic Inter-Society Consensus) A and B lesions versus TASC C and D lesions. METHODS: Based on a prospectively maintained database, a retrospective analysis was conducted of 375 symptomatic patients (335 men; mean age 63+/-8 years) who underwent 438 interventions for aortoiliac arterial obstructions. Lesions were stratified according to the TASC II classification: 259 (59%) procedures involved TASC A/B lesions, while 113 (26%) were for TASC C and 66 (15%) for TASC D lesions. RESULTS: The baseline characteristics of patients with TASC A/B lesions differed significantly in the ankle-brachial index (ABI), occurrence of renal insufficiency, and lesion characteristics from those with TASC C or D lesions. Acute treatment success, defined as residual stenosis <30%, was 100%, 96%, 93%, and 100% for TASC A, B, C, and D lesions, respectively. The primary 1-year patency rate, which was 86% for the entire study cohort, was similar for all TASC classifications (89%, 86%, 86%, 85% for TASC A to D lesions, respectively). In the TASC A/B cohort, the 5-year event-free survival (70%) was not significantly better than in the C/D cohort (57%, p=0.124). The clinical outcome, as measured by Rutherford stage and ABI, improved significantly in all TASC subgroups after successful intervention and was maintained up to 1 year. Stenting was an independent predictor for lower restenosis rates (HR 0.517, 95% CI 0.317 to 0.842; p=0.008). CONCLUSION: In experienced hands, endovascular therapy of aortoiliac lesions can be successfully performed with sustained long-term outcome independent of the TASC II classification, even in class D lesions.

Arterial puncture closure using a clip device after transpopliteal retrograde approach for recanalization of the superficial femoral artery.

PURPOSE: To report the safety and efficacy of a clip device to close retrograde popliteal artery puncture sites used in recanalization of the superficial femoral artery (SFA). METHODS: From January 2005 to March 2007, 28 patients (20 men; mean age 66+/-10 years) with stable chronic peripheral artery disease were treated for chronic total SFA occlusion. All patients received aspirin and clopidogrel and were heparinized during the procedure. After failed antegrade recanalization, the SFA was revascularized via a retrograde transpopliteal access. The StarClose Vascular System was used to seal the popliteal artery puncture site. RESULTS: All (100%) interventions were finished successfully, and hemostasis was secured with the StarClose device in all cases. There was 1 (3.6%) major complication with the StarClose system: a transient popliteal artery occlusion induced by plaque shift during sheath removal, which was corrected with balloon angioplasty via the femoral access. Three (10.8%) small hematomas (<5 cm) occurred at the puncture site without causing significant patient discomfort. CONCLUSION: In this small experience, the StarClose Vascular Closure System appeared to be an effective and safe sealing device after percutaneous transpopliteal interventions. Plaque shifting leading to stenosis or occlusion at the puncture site can occur.

Initial experience with directed laser atherectomy using the CLiRpath photoablation atherectomy system and bias sheath in superficial femoral artery lesions.

PURPOSE: To report a safety and efficacy study of directed excimer laser atherectomy with the Bias Sheath guiding catheter to create larger lumens in the superficial femoral artery (SFA). METHODS: Fourteen patients (9 men; mean age 66+/-9 years, range 46-76) with chronic lower limb ischemia (Rutherford class 2 to 5) referable to SFA stenoses were treated with the 8-F-compatible Bias Sheath and a 1.7- or 2.0-mm laser catheter. Eight (57%) lesions were de novo and 6 (43%) were in-stent restenoses (ISR). Mean diameter stenosis was 96%+/-8% (range 80%-100%; 10 total occlusions), and mean lesion length was 126+/-78 mm (range 30-290). The primary study endpoint was laser success, defined as <50% angiographic residual stenosis post-laser, without major perforations. RESULTS: The primary endpoint was achieved in 8 (57%) lesions; all patients underwent additional balloon angioplasty, which achieved an angiographic residual stenosis <30% in all. Three lesions could not be completely traversed with the study device. Two dissections were detected after Bias Sheath application; 1 required stenting. There were 2 embolic events (specific to the antegrade device design); both were treated with aspiration therapy. Intravascular ultrasound (IVUS)-based minimal lumen diameters were 0.23+/-0.2 mm (range 0-1.0) at baseline and 3.2+/-0.8 mm after Bias Sheath application. Rutherford category improved at 1 month in 10 (71%) patients. One patient remained unchanged, another worsened (category 2 to 3), 1 died, and the fourth was not examined. The ankle-brachial index improved from 0.41+/-0.18 at baseline to 0.79+/-0.19 at discharge and to 0.80+/-0.19 at 1 month. Primary 1-month patency (<50% restenosis by duplex) was 85% (11/13 lesions). CONCLUSION: SFA lesions, including ISR, can be treated in the majority of cases with directed laser atherectomy, significantly reducing plaque burden as measured by IVUS. Embolization was attributed to device-specific features of the prototype antegrade sheath design, which was discontinued. Larger studies are mandatory to document the long-term technical and clinical impact of this new device.

Percutaneous rotational and aspiration atherectomy in infrainguinal peripheral arterial occlusive disease: a multicenter pilot study.

PURPOSE: To report a safety and efficacy study of the first rotational aspiration atherectomy system (Pathway PV) for the treatment of arterial lesions below the femoral bifurcation. METHODS: From December 2005 to February 2006, 15 patients (9 men; mean age 71+/-9 years) with Rutherford stage 2 to 5 lower limb ischemia were enrolled at 3 study sites. Target lesions were in the superficial femoral (n = 7, 47%), popliteal (n = 7, 47%), and posterior tibial (n = 1, 6%) arteries. Mean diameter stenosis was 97%+/-10%; mean lesion length was 61+/-62 mm (range 5-250). The primary study endpoint was the 30-day serious adverse event (SAE) rate. RESULTS: Interventional success (residual stenosis <30%) was achieved in all lesions (100%). Stand alone atherectomy was performed in 6 (40%) patients, adjunctive balloon angioplasty in 7 (47%), and stenting/endografting in 2 (13%). The SAE rate at 30 days was 20% (3/15), including 1 perforation due to an unrecognized displacement of the guidewire (sealed with an endograft), 1 false aneurysm at the puncture site (successful duplex-guided compression therapy), and 1 dissection in conjunction with a distal embolism (stent implantation and aspiration thrombectomy). Primary patency rates measured by duplex ultrasound at 1 and 6 months were 100% and 73%, respectively; the TLR rate was 0% after 6 months. The ankle-brachial index increased significantly from 0.54+/-0.3 at baseline to 0.89+/-0.16, 0.88+/-0.19, and 0.81+/-0.20 (p<0.05) at discharge, 1 month, and 6 months, respectively. Mean Rutherford categories were 2.92+/-1.19 (range 1-5), 0.64+/-1.12 (range 0-1), and 0.83+/-1.33 (range 0-3) at the same time points (p<0.05). CONCLUSION: The application of this new atherectomy device was feasible in all cases. The serious adverse event rate was moderate; however, all events were solved during the index procedure. The 0% 6-month TLR rate is promising.

Treatment of instent restenosis following stent-supported renal artery angioplasty.

OBJECTIVES: We prospectively studied the long-term outcome of endovascular treatment of instent renal artery stenosis (IRAS). BACKGROUND: Restenosis is a considerable drawback of stent-supported angioplasty of renal artery stenosis especially in small vessel diameters. The appropriate treatment strategy is not yet defined. PATIENTS AND METHODS: During a 10-year period 56 consecutive patients (65 lesions) with their first IRAS were included in a prospective follow-up program (mean follow-up 53 +/- 25 months, range 6-102). Primary endpoint of the study was the reoccurence of IRAS (>or= 70%) after primarily successful treatment of the first IRAS determined by duplex ultrasound. RESULTS: Primary success rate was 100%, no major complication occurred. Nineteen lesions were treated with plain balloon angioplasty (group 1, 30%), 42 lesions with stent-in-stent placement (group 2, 65%) using various bare metal balloon expandable stents, and 4 lesions with drug-eluting stent angioplasty (group 3, 6%). During follow-up, overall 21 lesions (32%) developed reoccurence of IRAS: n = 7/19 in group 1 (37%), n = 14/42 in group 2 (33%), and n = 0/4 in group 3 (0%; P = 0.573). Reoccurence of IRAS was more likely to occur in smaller vessel diameters than in larger ones [3-4mm: 4/7 (57%); 5 mm: 11/26 (42%); 6 mm: 5/25 (20%); 7 mm: 1/7 (14%), P = 0.088]. Multivariable analysis found bilateral IRAS and IRAS of both renal arteries of the same side in case of multiple ipsilateral renal arteries as independent predictors for reoccurence of IRAS. CONCLUSION: Treatment of IRAS is feasible and safe. The data demonstrate a nonsignificant trend towards lower restenosis with restenting of IRAS versus balloon angioplasty of IRAS. Individual factors influence the likelihood of reoccurence of IRAS.

Treatment of reoccurring instent restenosis following reintervention after stent-supported renal artery angioplasty.

BACKGROUND: Reoccurrence of restenosis following angioplasty of renal instent restenosis is a considerable drawback of stent-supported angioplasty of renal artery stenosis especially in small vessel diameters. We therefore prospectively studied the long-term outcome of different techniques of endovascular treatment of reoccurrence of instent renal artery restenosis after primarily successful reangioplasty focusing on the impact of covered and drug eluting stents, respectively. PATIENTS AND METHODS: The study included 31 consecutive patients (33 lesions) presenting with their at least second instent restenosis following renal artery stenting who were included in a prospective follow-up program (mean follow-up 36+/-25 months, range 1-85). Primary endpoint of the study was the reoccurrence rate of instent stenosis after primarily successful treatment of instent restenosis determined by duplex ultrasound. RESULTS: Primary success rate was 100%, no major complication occurred. Seven lesions were treated with balloon angioplasty (21%, group 1), 7 lesions with stent-in-stent placement (21%, group 2), 6 lesions with placement of a covered stent (18%, group 3), 3 lesions with a cutting balloon (9%, group 4), and 10 lesions with placement of a drug eluting stent (31%, group 5). During follow-up, overall 12 lesions (36%) developed reoccurrence of instent restenosis: n=5 in group 1 (reoccurrence rate 71%), n=3 in group 2 (43%), n=1 in group3 (17%), 3 in group 4 (100%), and n=0 in group 5 (0%). Treatment with a cutting balloon was the only significant predictor of restenosis (hazard ratio 32.3 (95% CI, 3.3-315.0); P<0.001). CONCLUSION: Treatment of at least second renal artery instent restenosis is feasible and safe. Balloon angioplasty and the implantation of a bare metal stent, a covered stent, or a drug eluting stent seemed to offer favorable long-term patency, whereas cutting balloon angioplasty resulted in a very high rate of restenoses and should therefore be discouraged for this indication.

Two-year results after directional atherectomy of infrapopliteal arteries with the SilverHawk device.

PURPOSE: To report the 12- and 24-month results after directional atherectomy (DA) of below-the-knee (BTK) arterial lesions with the SilverHawk device. METHODS: Forty-nine BTK lesions in 36 patients (58% men; mean age 70+/-11 years) with peripheral occlusive disease of the lower limbs were treated with DA; 19 (53%) of the limbs were classified with Rutherford-Becker 4 or 5 ischemia. Target lesions were in the popliteal artery (n = 6, 12%), tibioperoneal trunk (n = 25, 51%), peroneal artery (n = 10, 20%), anterior tibial artery (n = 5, 10%), and posterior tibial artery (n = 3, 6%). Nine (18%) lesions were located in a stent. Twelve lesions extended to 2 artery segments. The average degree of diameter stenosis was 89%+/-10% (range 70%-100%); there were 11 (22%) occlusions. The mean lesion length was 48+/-28 mm. RESULTS: Sixteen (33%) lesions were treated after predilation; 33 (67%) lesions were treated with primary DA. All but 1 (2%) lesion could be treated with DA. In 19 (39%) lesions, additional balloon angioplasty was performed, and 2 (4%) lesions required stent implantation as a result of dissection. The mean stenosis diameter after DA was 12%+/-18% (range 0%-100%). After additional therapy, the mean stenosis diameter was 8%+/-9% (range 0%-100%). A residual stenosis

[Quality of antithrombotic therapy in patients with chronic atrial fibrillation: the AFib Trial]. / Qualität der antithrombotischen Therapie bei chronischem Vorhofflimmern: AFib-Studie.

BACKGROUND: Large randomised studies have definitely shown that oral anticoagulation effectively reduces thromboembolic complications, e.g. stroke, in patients with chronic non-valvular atrial fibrillation (AFib). However, less than 50% of the eligible AFib patients receive anticoagulation, although their risk of thromboembolic disease is increased 5-7 fold as compared to individuals who have a regular sinus rhythm. This is the reason why undertreatment needs to be evaluated and addressed. In Germany, data on the antithrombotic therapy of these patients are sparse, national guidelines are lacking. AIM OF THE STUDY: This prospective cohort study is the first one to evaluate the quality of antithrombotic prevention in two groups of AFib outpatients in two different, socio-demographically comparable regions of Germany (Südbaden and Südwürttemberg) over a period of several years. Quality of care is defined as the percentage of AFib patients in a certain region treated according to international guidelines. If the percentage in both cohorts does not exceed 80%, guidelines are to be developed and implemented in Südwürttemberg on consideration of the specific treatment conditions in this region; their applicability is to be evaluated later. METHODS: Office-based specialists of internal and general medicine are currently recruiting 200 AFib patients in each study region for documentation of their clinical data. Besides the quality of antithrombotic chemoprevention, relevant problems emerging in antithrombotic therapy in an ambulant setting will be identified. In the area of intervention (Südwürttemberg) experts and office-based physicians will exclusively develop evidence-based guidelines and disseminate them among doctors. Six months after the implementation of these guidelines in Südwürttemberg, their influence on prescribing patterns will be determined by comparing the proportion of anticoagulated AFib patients in Südwürttemberg to that of the control cohort (Südbaden). In addition, secondary outcomes of interest include deaths, days of hospitalisation, and incidence of stroke or bleeding episodes for different antithrombotic treatments.