Candesartan treatment for peripheral occlusive arterial disease after stent angioplasty : a randomised, placebo-controlled trial.

OBJECTIVES: In this prospective, double-blind, placebo-controlled study we observed the influence of treatment with candesartan 8mg on restenosis rates after stent implantation into the femoral artery 6 months after percutaneous transluminal angioplasty (PTA). We hypothesised that angiotensin II type 1 (AT1)-receptor blockade with candesartan would reduce restenosis rates by reducing angiotensin II-mediated intima hyperproliferation within the stented vessel segment in patients with peripheral occlusive disease. PATIENTS AND METHODS: Eighty-seven patients with peripheral occlusive arterial disease stage IIb who had been successfully treated with PTA and stent implantation were randomised to receive orally either candesartan 8mg (n = 44) or placebo (n = 43). Follow-up included evaluation of the degree of stenosis and thickness of the intima-media complex (primary endpoint). In addition, thickness of the interventricular septum, crurobrachial pressure ratios, and pain-free walking distance were determined (secondary endpoints). RESULTS: The degree of stenosis after 6 months was not significantly different between the groups studied (35.9 +/- 39.6% for candesartan vs 36.0 +/- 38.4% for placebo). Relevant restenosis including stent occlusions was found in nine patients (20.5%) in the candesartan group and in ten patients (23.3%) in the placebo group. The thickness of the intima-media complex 6 months after stent implantation was 1.60 +/- 0.32mm in the candesartan group and 1.64 +/- 0.32mm in the placebo group (not significant). There were no differences in secondary endpoints between the treatment groups. Controls after 3 months (20.9 +/- 33.6% for candesartan vs 27.6 +/- 38.3% for placebo; p = 0.39) and 9 months (44.1 +/- 40.8% for candesartan vs 47.7 +/- 37.2% for placebo; p = 0.67) of therapy revealed a lower degree of stenosis in patients treated with candesartan. CONCLUSIONS: Although not significant, candesartan treatment tended to improve the prognostic benefits after stent implantation, suggesting that an antiproliferative effect after stenting may need higher doses than an antihypertensive effect of the drug. This hypothesis requires confirmation in further prospective studies with higher daily doses of candesartan, which are already in progress.

Potential use of a low-molecular-weight heparin to prevent restenosis in patients with extensive wall damage following peripheral angioplasty.

The long-term outcome of primary successful percutaneous transluminal angioplasty (PTA) for patients with peripheral occlusive arterial disease (POAD) is frequently compromised by the development of restenosis, especially when extensive dissections result from the angioplastic procedure. Unfortunately, prevention of the occlusive process by means of drugs such as antithrombotics, anticoagulants, thrombolytics, corticosteroids, lipid reducers, or cytostatics has not been demonstrated convincingly. The authors sought to clarify whether such patients could benefit from the postsurgical administration of low-molecular-weight heparin. A total of 172 POAD patients with extensive dissections after PTA in the pelvic or upper leg regions were randomized for 7-day post-PTA intravenous treatment with either full heparinization or nadroparin calcium followed by adjunctive oral aspirin for 6 months. The primary outcome measure was the degree of stenosis (normal findings; stenosis < 50%, > 50%, > 80%, occlusion) before and after angioplasty, as well as 3 weeks and 3 and 6 months after dilation; secondary efficacy criteria included changes in the Fontaine stage and in the crurobrachial ratio. No significant treatment-related differences were found at the 3 post-PTA follow-up examinations with regard to the degree of stenosis. This was also the case for the subgroup of patients (n = 62) who had undergone angioplasty in the pelvic region. By contrast, when angioplasty was performed in the superficial femoral artery (n = 110), the degree of restenosis was significantly lower (p<0.01) among patients receiving nadroparin calcium compared to those given heparin at week 3, month 3, and month 6. No intergroup differences emerged for secondary outcome measures in the long term or for safety parameters. These preliminary results indicate that patients with extensive dissections after PTA treatment for POAD in the upper leg region might benefit from a reduction in the rate of restenosis by administration of 7-day weight-adjusted nadroparin calcium.

Short- and long-term results of abciximab versus aspirin in conjunction with thrombolysis for patients with peripheral occlusive arterial disease and arterial thrombosis.

Acute peripheral occlusive arterial disease is an important cause of morbidity and mortality, particularly among older persons. Catheter-directed thrombolytic therapy is the treatment of choice but has limitations: long lytic times, occlusions refractory to thrombolysis, and a high rate of restenosis. We conducted a pilot study to evaluate the use of the platelet GP IIb/IIIa receptor antagonist abciximab versus aspirin in conjunction with thrombolysis in patients with acute peripheral occlusive arterial disease associated with arterial thrombosis. A total of 84 patients were randomized into two equal groups to receive 5 mg recombinant tissue plasminogen activator intravenously and 500 IU heparin/hour along with either 500 mg acetylsalicylic acid or a bolus of 0.25 mg/kg abciximab followed by 10 microg/min abciximab over 12 hours (heparin reduced to 250 IU/hour). Primary efficacy criteria included the number of rehospitalizations, reinterventions, and amputations during the following 6 months. Secondary endpoints were the changes in the Fontaine stage, Bollinger index (vessel occlusion), ankle-to-brachial ratios, distance to claudication after 6 months, and the duration of the initial local lysis treatment. Adjunctive use of abciximab reduced the rates of rehospitalization, reinterventions, and amputations versus results with the use of aspirin (10 vs 14 occurrences, respectively; 9 vs 11; 3 vs 5; when summed, intergroup difference p < 0.05). Secondary peripheral occlusive arterial disease variables became highly significant versus aspirin (p < 0.001 or greater) at 3 and 6 months after treatment. The duration of lysis was markedly shorter upon addition of abciximab versus aspirin (75 vs 110 min; p < 0.001). No major bleeding complications or embolisms occurred. These preliminary results indicate that abciximab may have a useful role when used adjunctively with a thrombolytic agent in older persons with acute peripheral occlusive arterial disease and arterial thrombosis.

Short- and long-term results after thrombolytic treatment of deep venous thrombosis.

OBJECTIVES: The goal of this study was to assess the short- and long-term efficacy of different thrombolytic therapy regimens in patients with leg or pelvic deep venous thrombosis (DVT). BACKGROUND: It is unclear whether locoregional or systemic thrombolysis is superior in treating acute leg DVT or even whether lysis is more effective than anticoagulation therapy in preventing postthrombotic syndrome. METHODS: A total of 250 patients averaging 40 years of age with acute DVT were randomized into five groups to receive full heparinization (1,000 IU/h) and compression treatment, with four groups also administered locoregional tissue plasminogen activator (20 mg/day) or urokinase (100,000 IU/day) or systemic streptokinase (3,000,000 IU daily) or urokinase (5,000,000 IU daily). All groups then received anticoagulation and compression treatment for one year. Primary efficacy criteria included the change after one year in the number of closed vein segments and the occurrence of postthrombotic syndrome. RESULTS: Systemic thrombolytic therapy significantly reduced the number of closed vein segments after 12 months in patients with acute DVT compared with conventional treatment (p < 0.05). Postthrombotic syndrome also occurred with less frequency in systemically treated patients versus controls (p < 0.001). High-dose thrombolysis led to better rates of complete recanalization after seven days (p < 0.01) than locoregional lysis. However, 12 patients receiving thrombolysis (9 systemic, 3 local) suffered major bleeding complications; 9 patients on systemic treatment developed pulmonary emboli. CONCLUSIONS: Systemic thrombolytic treatment for acute DVT achieved a significantly better short- and long-term clinical outcome than conventional heparin/anticoagulation therapy but at the expense of a serious increase in major bleeding and pulmonary emboli. Given the inherent risks for such serious complications, systemic thrombolysis, although effective, should be used selectively in limb-threatening thrombotic situations.

Comparative results of thrombolysis treatment with rt-PA and urokinase: a pilot study.

BACKGROUND: The aim of the following prospective study was to investigate whether patients benefited from locoregional lysis treatment of recent deep leg vein thrombosis after 1 year. PATIENTS AND METHODS: The prospective study included 69 patients aged between 22 and 58 years, in whom recent lower leg vein and popliteal vein thromboses were diagnosed by phlebography. Patients were randomized to one of three treatment groups: one group was treated for a maximum of 7 days with full heparinization and daily dose of 20 mg rt-PA administered locoregionally over a period of 4 hours; a second group received 100,000 IU/h urokinase locoregionally for a maximum of 7 days, in addition to full heparinization; and in the third group (control group), intravenous heparin infusions after PTT constituted the only form of treatment. All patients were given phenprocoumon from day 7 and received compression treatment. Before treatment began and before the course of phenprocoumon started, phlebography and colour duplex sonography examinations were carried out. After 12 months, follow-up duplex sonography was conducted to evaluate the reflux times over the popliteal vein and the degree of patency of the deep leg veins. RESULTS: Complete lysis was achieved in 6 of 22 patients in the recombinant tissue plasminogen activator (rt-PA) group and in 11 of 22 patients in the urokinase group. At follow-up examination after 12 months, there were serious post-thrombotic changes in 14 of 22 patients in the rt-PA group, in 9 of 22 patients in the urokinase group and in 15 of 22 patients in the group of patients who received no lysis treatment. CONCLUSION: Patients with recently formed thromboses in the lower leg and popliteal veins who underwent 7 days of locoregional lysis treatment with urokinase demonstrated significantly fewer clinical symptoms of post-thrombotic syndrome after 1 year than those who received locoregional treatment with rt-PA over a similar period or a control group treated with anticoagulants only.

Effect of high dose verapamil on restenosis after peripheral angioplasty.

OBJECTIVES: We sought to determine whether treatment with high dose verapamil prevents restenosis in patients at high risk for reoccurrence after successful percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Restenosis is the major limitation of PTCA. Calcium antagonists have demonstrated some potential as inhibitors of this process. METHODS: A total of 98 patients with peripheral occlusive arterial disease (POAD), stable angina pectoris, mild hypertension and at least one additional risk factor increasing the likelihood of restenosis after angioplasty were selected for this placebo-controlled, double-blind, randomized trial. Verapamil (240 mg twice daily) or placebo was taken for 6 months. Efficacy variables assessed before and after angioplasty and at 6 weeks and 6 months after PTCA included thickness of the intima/media complex degree of stenosis, interventricular septal thickness, crurobrachial pressure ratios of dorsalis pedis and posterior tibial arteries, distance to claudication and total vessel diameter. RESULTS: No significant intergroup differences emerged before or immediately after PTCA. Six weeks after angioplasty, a significant thickening of the intima/media complex in the treated vascular segment of 14.3% occurred in the placebo group versus 0% among verapamil patients (p < 0.01). At 6 months, the intima/media thickness was 35.7% greater in the placebo group but had decreased by 14.3% in the verapamil group (p < 0.001). At 6 months, a marked reduction in septal thickness was observed in the verapamil group versus that in the placebo group (p < 0.001). The rate of restenosis was also significantly lower in the verapamil group (p < 0.001). Few minor side effects were reported. CONCLUSIONS: In patients with POAD at increased risk for restenosis, the administration of high dose verapamil prevented recurrent stenosis for 6 months after successful peripheral angioplasty and was well tolerated.