Fibrin Sealant TISSEEL Lyo as a haemostatic agent in vascular surgery: Results of randomized, controlled, patient-blinded, multicentre clinical study in the Russian population.

BACKGROUND: This phase III, controlled, patient-blinded, multicentre study in two parallel, equal-sized treatment groups compared the efficacy and safety of TISSEEL Lyo, fibrin sealant versus Manual Compression (MC) with surgical gauze pads for use as a haemostatic agent in patients who underwent vascular surgery in Russia. METHODS: Adult patients, both genders, who received peripheral vascular expanded polytetrafluoroethylene conduits and had suture line bleeding after surgical haemostasis were enrolled. Patients were randomized to be treated with TISSEEL Lyo or MC. The bleeding needed additional treatment and had to be assessed as grade 1 or 2 bleeding according to the Validated Intraoperative Bleeding scale. The primary efficacy endpoint was the proportion of patients achieving haemostasis at 4 min after treatment application (T4) at the study suture line, which was maintained until the closure of the surgical wound. The secondary efficacy endpoints included the proportion of patients achieving haemostasis at 6 min (T6) and 10 min (T10) after treatment application at the study suture line, which was maintained until closure of the surgical wound, as well as the proportion of patients with intraoperative and postoperative rebleeding. Safety outcomes included incidence of adverse events (AEs), surgical site infections and graft occlusions. RESULTS: A total of 110 patients were screened; 104 patients were randomized: (TISSEEL Lyo: 51 [49%] patients; MC: 53 [51%] patients). T4 haemostasis was achieved in 43 (84.3%) patients in the TISSEEL Lyo group and in 11 (20.8%) patients in the MC group (p < 0.001). Significantly more patients in TISSEEL Lyo group achieved the haemostasis at T6 (relative risk (RR) of achieving haemostasis 1.74 [95% confidence interval (CI) 1.37; 2.35]) and T10 (RR 1.18 [95% CI 1.05; 1.38]) versus MC. No one had intraoperative rebleeding. Postoperative rebleeding was reported only in one patient in the MC group. No treatment-emergent serious AEs (TESAEs) related to TISSEEL Lyo/MC, TESAEs leading to withdrawal and TESAEs leading to death were reported in patients during the study. CONCLUSIONS: Data demonstrated TISSEEL Lyo had clinically and statistically significant superiority to MC as a haemostatic agent in vascular surgery at all measured time points including 4, 6 and 10 min and had proven to be safe.

Efficacy and safety of Actovegin in the treatment of intermittent claudication: results of an international, multicenter, placebo-controlled, randomized, phase IIIb clinical trial (APOLLO).

BACKGROUND: This study aimed to assess the efficacy and safety of Actovegin for the treatment of patients with Fontaine stage IIB peripheral arterial disease (PAD). METHODS: The study included 366 patients with Fontaine stage IIB PAD from 19 centers (Russia, Georgia, Kazakhstan). Placebo or Actovegin (1200 mg daily [QD]) were administered intravenously for two weeks, followed by a 10-week course of oral administration (placebo or Actovegin 1200 mg QD). The primary efficacy outcome was percentage change in the initial claudication distance (ICD) by week 12. Secondary outcomes included percent and absolute changes in ICD, absolute claudication distance (ACD) and changes in Quality of Life (QoL) assessed by the SF-36 Mental Health Score. RESULTS: The increase in ICD after 12 weeks of Actovegin treatment was 29.19% (LS mean [Actovegin vs. placebo]; 95% CI: 9.35-49.02; P=0.0041). The percentage increase in ICD at 24 weeks was 35.51% (LS mean; 95% CI: 10.96-60.05; P=0.0047), which correspond to an increase in absolute ICD of 41.22 m (LS mean; 95% CI: 16.77-65.66; P=0.0010). The percentage increase in ACD after 24 weeks was 36.47% compared with the baseline (LS mean; 95% CI: 10.07-62.88; P=0.0069), which corresponded to an absolute increase in ACD of 50.92 m (LS mean; 95% CI: 18.35-83.49; P=0.0023). A statistically significant improvement in QoL with Actovegin compared with placebo was demonstrated within 24 weeks (LS mean 2.28; 95% CI: 0.88-3.68; P=0.0015). Actovegin demonstrated an acceptable safety and tolerability profile with minor differences from placebo. CONCLUSIONS: The results of this 12-week course of Actovegin demonstrated its superiority over placebo in the increase in ICD and ACD at weeks 2, 12 and 24 from the start of treatment. Actovegin has an acceptable safety and tolerability profile.

EVAR as a treatment option for high-risk nonagenarians with complicated abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) is a life-threatening disease, with an extremely high risk of death when ruptured. With the increase in life expectancy AAA is becoming more prevalent in aging patients. Elective and emergency procedures in elderly patients with AAA are becoming more common, but the indications for aortic repair and outcomes in geriatric patients are debatable. In our report, we present long-term results of a successful endovascular aortic repair (EVAR) of a ruptured juxtarenal aortic aneurysm complicated by hypovolemia and myocardial infarction in a 92-year-old patient. No endoleaks or bleedings were detected with CT angiography in the post-operative period. After two years following the procedure, the patient is doing well and can take care of himself; there was no disease progression as confirmed by ultrasonography. In conclusion, complicated abdominal aortic aneurysms in nonagenarians can be successfully treated by EVAR with fine long-term results.

Coagulation Factor Activity and Hemostatic Markers of Endothelial Dysfunction in Patients with Peripheral Arterial Disease.

PURPOSE: We aimed to evaluate the impact of intrinsic coagulation factors and hemostatic markers of endothelial dysfunction on complications in patients with atherosclerotic peripheral arterial disease (PAD). MATERIALS AND METHODS: This prospective study enrolled 120 PAD patients at Fontaine stages 2b to 3 who underwent open surgical, endovascular, or conservative treatment. Coagulation factors (FVIII, FIX, and FXI) and endothelial hemostatic markers, including von Willebrand factor (vWF) activity and level, soluble endothelial protein C receptor, and plasminogen activator inhibitor-1 (PAI-1) levels, were assessed. RESULTS: At 3 months after open bypass grafting, activity of FVIII significantly increased from a median of 175% to 233% (P<0.001). At 3 months after endovascular treatment, the activities of FVIII, FIX, and FXI significantly increased from medians of 157%, 180%, and 156% to 184%, 218%, and 181%, respectively (P<0.05). Six patients with increased FVIII activity developed bypass graft thrombosis. Four patients in the endovascular group and three patients in the conservative treatment group with increased activity of vWF developed myocardial infarction (P=0.049). The subjects who developed restenosis had increased vWF activity (P=0.023) and decreased nitric oxide metabolite levels (P=0.003). Three subjects who received conservative treatment and developed PAD progression at 12 months had increased PAI-1 activity (P=0.028). CONCLUSION: Patients with advanced PAD had a hypercoagulable status, and performance of open or endovascular revascularization was associated with further hypercoagulability. Increased activity of coagulation factors and altered levels of hemostatic markers of endothelial dysfunction were associated with PAD complications such as graft thrombosis, myocardial infarction, disease progression, and restenosis.

pCMV-vegf165 Intramuscular Gene Transfer is an Effective Method of Treatment for Patients With Chronic Lower Limb Ischemia.

Effective treatment of chronic lower limb ischemia is one of the most challenging issues confronting vascular surgeons. There are a number of choices available to the vascular surgeon. Open or endovascular revascularization is the treatment of choice when applicable. Current pharmacological therapies play an auxiliary role and cannot prevent disease progression. Therefore, new methods of treatment are needed. We conducted a phase 2b/3 multicenter randomized controlled clinical trial of the intramuscular transfer of a plasmid DNA encoding vascular endothelial growth factor (VEGF) 165 with cytomegalovirus promotor (CMV) in patients with atherosclerotic lower limb ischemia. A total of 100 patients were enrolled in the study, that is, 75 patients were randomized into the test group and received 2 intramuscular injections of 1.2 mg of pCMV-vegf165, 14 days apart together with standard pharmacological treatment. In all, 25 patients were randomized into the control group and received standard treatment only. The following end points were evaluated within the first 6 months of the study and during a 1.5-year additional follow-up period: pain-free walking distance (PWD), ankle-brachial index (ABI), and blood flow velocity (BFV). The pCMV-vegf165 therapy appeared to be significantly more effective than standard treatment. The PWD increased in the test group by 110.4%, 167.2%, and 190.8% at 6 months, 1 year, and 2 years after treatment, respectively. The pCMV-vegf165 intramuscular transfer caused a statistically significant increase in ABI and BFV. There were no positive results in the control group. Thus, pCMV-vegf165 intramuscular gene transfer is an effective method of treatment of moderate to severe claudication due to chronic lower limb ischemia.