Maintain Vessel Patency Research Articles

An integrated view of potassium homeostasis

n engl j med 373;18 nejm.org october 29, 2015 1786 was a similar trend favoring patency in patients who received statins. Also, treatment with a drugcoated balloon was associated with improved patency over a conventional balloon in both patients receiving statins and those not receiving statins. The beneficial effects of statins may be additive to those of drug-coated balloons. In summary, our trial showed that angioplasty with a drug-coated balloon maintained vessel patency that was superior to that of angioplasty with a standard balloon, and it showed superiority for a functional end point on the Walking Impairment Questionnaire. We agree that all patients should receive maximum tolerated doses of statins and that data from larger studies are lacking to confirm the beneficial effects on quality of life and physical functioning conferred by angioplasty with a drug-coated balloon over conventional angioplasty with a standard balloon.

Iatrogenic Type A Aortic Dissection: Conservative Treatment after Complicated Left Subclavian Artery Recanalization

used bare stents. We chose the EXCLUDER iliac stentgraft (W.L. Gore and Associates) in both cases because of its availability and because it has proven to have low permeability when used in abdominal aortic aneurysm repair. The graft provided an effective seal across the perforation, with creation of a new intact flow lumen. In conclusion, the use of covered stents for treatment of traumatic venous injuries provided a safe and effective way to address the acute extravasation. It may prove to be a first-line approach in this setting to maintain vessel patency and avoid iatrogenic complications.

Successful treatment of aortic root rupture following transcatheter aortic valve implantation in a heavily calcified aorta: A novel approach to a serious complication

Aortic root rupture during transcatheter aortic valve implantation (TAVI) is an uncommon but almost uniformly fatal complication. We describe a novel surgical management of this complication using a combination of pledgeted sutures and prolonged direct digital compression with biomatrix and lattice adjuncts. Furthermore, our patient underwent percutaneous coronary intervention with endothelial progenitor cell-capturing stents, which facilitated TAVI to be performed off clopidogrel therapy. We believe the use of these stents reduced the severity of hemorrhage following aortic root rupture and helped maintain vessel patency following prolonged hypotension.

Can Myocardial Infarct Size Be Reduced by Mechanically Unloading the Left Ventricle?

Great strides have been made in the treatment of acute myocardial infarction (MI). Improved outcomes and reduced mortality are largely the result of opening the occluded infarct artery as soon as possible and keeping it open. Early reperfusion consistently reduces myocardial infarct size in both experimental animal models and in patients. Article see p 328 Despite the advances in stenting of the occluded coronary artery and shortening of the door-to-balloon time, 1 month mortality postinfarction still hovers at ≈15%, and post-MI heart failure remains problematic. Therefore, there is still a need to try to further reduce myocardial infarct size in 2013. Initial concepts focused on reducing myocardial infarct size by improving the imbalance between O2/nutrient supply and O2/nutrient demand of the heart (Table). Improving O2 supply by inducing early reperfusion with thrombolytic therapy, then angioplasty, and now stenting has been successful and dual-antiplatelet therapy and possibly the addition of anticoagulant therapy have further improved clinical outcomes, maintained vessel patency, and reduced stent thrombosis. Other techniques to improve O2/nutrient supply such as hyperoxemia and erythropoietin have shown benefit in some but not all studies. Antianginal agents that vasodilate the coronary arteries and may improve coronary flow, such as nitrates and calcium blockers, in general, have failed to reduce myocardial infarct size in clinical trials. View this table: Table. Therapies That May Reduce Infarct Size by Either Improving O2 Supply or Reducing O2 Demand Although restoring O2 supply reduces ischemic cardiac damage resulting from MI, attempts at reducing myocardial infarct size by reducing O2 demand have yielded mixed results. Early clinical studies with β-blockers in the pre-reperfusion era were negative. However, chronic β-blockers post-MI were suggested to reduce fatal ventricular arrhythmias, reduce reinfarction, and limit left ventricle (LV) remodeling and post-MI heart failure and death. …

Hirudin and S18886 Maintain Luminal Patency After Thrombolysis With Alfimeprase

An optimal strategy to improve reperfusion in patients with arterial occlusions is a recognized clinical need. We hypothesized that hirudin (thrombin inhibitor) and S18886 [S18, thromboxane A(2) receptor (TP) antagonist] would improve blood flow and reperfusion rates after thrombolysis with the direct-acting fibrinolytic enzyme alfimeprase. In anesthetized beagles, carotid artery thrombosis was induced by electrolytic endothelial injury. After 30 minutes of occlusion, animals were administered vehicle, hirudin, and/or S18. Carotid artery blood flow was monitored for 90 minutes after the infusion of alfimeprase or recombinant tissue plasminogen activator (rt-PA). The onset to reperfusion was more rapid in animals treated with alfimeprase than in those treated with rt-PA. All the animals treated with hirudin + S18 + alfimeprase maintained vessel patency, and all vehicle-treated animals reoccluded. In animals treated with hirudin + S18 + alfimeprase, time to reocclusion and total reflow time after thrombolysis were longer compared with vehicle-treated animals. The quality and quantity of blood flow were most improved in animals treated with hirudin + S18 + alfimeprase. There were no significant differences in time to reocclusion, total reflow time, and quality and quantity of blood flow between vehicle + rt-PA-treated animals and hirudin + S18 + rt-PA-treated animals. Dual antithrombotic therapy with hirudin and S18 improves reperfusion after thrombolysis with alfimeprase but not rt-PA.

Endovascular Management of Iliac Vein Rupture During Percutaneous Interventions for Occlusive Lesions

Iatrogenic Iliac vein rupture is a rare and potentially lethal complication. We present herein two different clinical scenarios of iatrogenic iliac vein rupture that resulted from performing percutaneous endoluminal interventions to treat symptomatic veno-occlusive lesions. The first case was due to the presence of surgical clips from the patient's previous gynecologic surgery, which caused iliac vein compression and eventually led to acute deep vein thrombosis. The second case resulted from central venous outflow obstruction ipsilateral to a lower extremity arteriovenous dialysis access site. Both Iliac vein ruptures were the result of percutaneous attempts to correct the outflow lesion (delayed in the first case and acute in the second case). Hemorrhage was successfully controlled in both cases using a self-expandable Viabahn (W. L. Gore and Associates, Flagstaff, AZ) covered stent while maintaining vessel patency and resolving symptoms related to veno-occlusive disease.

Myocardial Infarction and Protection

Cardioprotection has been defined as a therapy that limits the infarct size during an acute myocardial infarction that may lead to better clinical outcomes. Various interventions have been investigated in the past to reduce myocardial infarct size with variable success. The best strategy till date to limit infarct size has been the early restoration of coronary blood flow, with percutaneous coronary interventionwhere available. Stenting following invasive reperfusion, especially in the early hours after an infraction has been found superior to all other available modalities of therapy. Attempt to decrease time from onset of symptoms to start of reperfusion and maintaining vessel patency has been proven to yield the best outcomes. Future studies powered to better assess clinical outcomes are needed for adjunctive therapy with stem cells and hypothermia.

Abstract 17260: Percutaneous Recanalization of Totally Occluded Pulmonary Veins After Pulmonary Vein Isolation

Background: Pulmonary vein total occlusion (PVO) is an uncommon complication of pulmonary vein isolation (PVI). We have previously published our early experience with diagnosis and treatment of PVO, and now describe mid-term follow-up of attempted recanalization. Methods: Patients with angiographic PVO were identified from our catheterization database. Medical records and catheterization reports were reviewed for: symptoms, flow to affected lung quadrant, time from PVI to diagnosis of PVO, anatomic characteristics of occluded veins, and procedural details. Patients with severely hypoplastic veins had staged intervention with initial balloon angioplasty followed by stenting 2-4 months later to allow for vessel growth. Symptoms, quadrant flow, and status of the vein at last follow-up were ascertained. Results: Between 6/2005 and 6/2011, 14 patients with PVO underwent attempted recanalization. Median age was 56.9 (0.2-67.3) years, weight 88 (5.0-111.4) kg. Symptoms included dyspnea in 11, cough in 4, hemoptysis in 5 with a mean NYHA class of 2.1 ± 0.8. Flow to affected lung quadrant was severely diminished at 5.9 ± 3.7%. Median time from PVI to recanalization attempt was 16.5 (2.0-62.7) months. Reference vessel diameter was 5.3 ± 2.0 mm and length of occluded segment 8.3 ± 6.0 mm. Recanalization results are summarized in Table 1. At median follow-up of 13.3 (0-41.3) months, 10 veins remain patent with minimal diameter of 6.1 ± 2.7 mm, reference diameter of 7.8 ± 3.1 mm, and flow to affected lung quadrant 12.3 ± 7.2%, all significantly greater than pre-intervention (p<0.03). Of 10 patients completing staged intervention, 5 have no symptoms and mean NYHA class decreased to 1.5 ± 0.7. Conclusions: PVO recanalization can be accomplished with reasonable acute and mid-term vessel patency and significant improvement in symptoms and flow to affected lung quadrant. However, recurrent stenosis is common and repeated interventions are often necessary to maintain vessel patency.

Multiobjective design optimisation of coronary stents

We present here a multi-objective and multi-disciplinary coronary stent design optimization paradigm. Coronary stents are tubular, often mesh-like, structures which are deployed in diseased (stenosed) artery segments to provide a scaffolding feature that compresses atheromatus plaque, hence restoring luminal area and maintaining vessel patency. A three variable geometry parameterisation of a CYPHER (Cordis Corporation, Johnson & Johnson co.) type stent is proposed to explore the functionality of a sequence of circumferential rings connected by ‘n’ shaped links. The performance of each design is measured by six figures of merit (objectives/metrics) representing (i) acute recoil, (ii) tissue stresses, (iii) haemodynamic disturbance, (iv) drug delivery, (v) uniformity of drug distribution, and (vi) flexibility. These metrics are obtained from computational simulations of (i) structural deformation through balloon inflated expansion of a stent into contact with a stenosed vessel, (ii) pulsatile flow over the deformed stent embedded in the vessel wall, (iii) steady-state drug distribution into the tissue, and (iv) flexibility of a stent in response to an applied moment. Design improvement is obtained by a multi-objective surrogate modelling approach using a non-dominated sorting genetic algorithm (NSGA-II) to search for an optimal family of designs. A number of trade-offs between the different objectives are identified. In particular a conflict between pairs of the following objectives are shown -- (a) volume average stress vs. recoil, (b) volume average drug vs. volume average stress, (c) flexibility vs. volume average stress, (d) flexibility vs. haemodynamic disturbance, (e) volume average drug vs. haemodynamic disturbance, and (f) uniformity of drug vs. volume average stress. Different paradigms to choose the optimal designs from the obtained Pareto fronts are presented and under each such paradigm, the optimal designs and there relative positions with respect to a representative CYPHER stent are shown. The methodology and the results of this work could potentially be useful in further optimisation studies and development of a family of stents with increased resistance to in-stent restenosis and thrombosis.

Catheter-directed thrombolytic therapy for thoracic deep vein thrombosis is safe and effective in selected patients with and without cancer

To assess the safety, feasibility and efficacy of catheter-directed thrombolysis for thoracic central venous thrombosis in both cancer and non-cancer patients. A retrospective case series of 68 patients, including 35 with active cancer and 33 without cancer, was analysed. They all received catheter-directed thrombolysis with alteplase or urokinase for symptomatic acute major thoracic vein thrombosis. Substantial clot lysis was obtained in 62 out of 68 patients (91%), the results being 88.6 and 93.8% for cancer and non-cancer patients respectively (P = 0.68). The mean infusion time in patients with and without cancer was 2.11 and 1.84 days respectively (P = 0.3259). Procedure-related complications occurred in two cancer patients (8.6%) and in seven non-cancer patients (21%) (P = 0.18). One cancer patient developed a fatal intracranial bleeding. Additional intervention after successful lysis was performed in cancer (n = 18; 51%) as well as in non-cancer patients (n = 29; 88%). Catheter-directed thrombolysis is a feasible and highly effective interventional procedure with an acceptable safety profile in selected patients with and without cancer for the treatment of symptomatic thoracic central venous thrombosis. In most cases, additional endovascular or surgical procedures are required to restore and maintain vessel patency after successful thrombolysis.

Rola badania dopplerowskiego w ocenie powikłań naczyniowych po cewnikowaniu serca z dostępu promieniowego lub udowego z użyciem StarClose – badanie w ramach RADIAMI II

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Kowalczuk A, Chodór P, Streb W, Kurek T, Kalarus Z, Zembala M. Original paperThe utility of duplex ultrasound scanning in reporting the vascular complications after heart catheterization performed from new arterial approaches – radial or femoral artery access with StarClose usage – a substudy of the RADIAMI II trial. Advances in Interventional Cardiology/Postępy w Kardiologii Interwencyjnej. 2010;6(3):112-116. doi:10.5114/pwki.2010.16351. APA Kowalczuk, A., Chodór, P., Streb, W., Kurek, T., Kalarus, Z., & Zembala, M. (2010). Original paperThe utility of duplex ultrasound scanning in reporting the vascular complications after heart catheterization performed from new arterial approaches – radial or femoral artery access with StarClose usage – a substudy of the RADIAMI II trial. Advances in Interventional Cardiology/Postępy w Kardiologii Interwencyjnej, 6(3), 112-116. https://doi.org/10.5114/pwki.2010.16351 Chicago Kowalczuk, Anetta M., Piotr Chodór, Witold Streb, Tomasz Kurek, Zbigniew Kalarus, and Marian Zembala. 2010. "Original paperThe utility of duplex ultrasound scanning in reporting the vascular complications after heart catheterization performed from new arterial approaches – radial or femoral artery access with StarClose usage – a substudy of the RADIAMI II trial". Advances in Interventional Cardiology/Postępy w Kardiologii Interwencyjnej 6 (3): 112-116. doi:10.5114/pwki.2010.16351. Harvard Kowalczuk, A., Chodór, P., Streb, W., Kurek, T., Kalarus, Z., and Zembala, M. (2010). Original paperThe utility of duplex ultrasound scanning in reporting the vascular complications after heart catheterization performed from new arterial approaches – radial or femoral artery access with StarClose usage – a substudy of the RADIAMI II trial. Advances in Interventional Cardiology/Postępy w Kardiologii Interwencyjnej, 6(3), pp.112-116. https://doi.org/10.5114/pwki.2010.16351 MLA Kowalczuk, Anetta M. et al. "Original paperThe utility of duplex ultrasound scanning in reporting the vascular complications after heart catheterization performed from new arterial approaches – radial or femoral artery access with StarClose usage – a substudy of the RADIAMI II trial." Advances in Interventional Cardiology/Postępy w Kardiologii Interwencyjnej, vol. 6, no. 3, 2010, pp. 112-116. doi:10.5114/pwki.2010.16351. Vancouver Kowalczuk A, Chodór P, Streb W, Kurek T, Kalarus Z, Zembala M. Original paperThe utility of duplex ultrasound scanning in reporting the vascular complications after heart catheterization performed from new arterial approaches – radial or femoral artery access with StarClose usage – a substudy of the RADIAMI II trial. Advances in Interventional Cardiology/Postępy w Kardiologii Interwencyjnej. 2010;6(3):112-116. doi:10.5114/pwki.2010.16351.

Temporary Endovascular Bypass: A Novel Treatment for Acute Stroke: Fig 1.

Intracranial stent placement is emerging as an effective treatment for acute stroke. As a means to avoid stent-associated complications and capitalize on stent-placement-related advantages, the concept of a "temporary endovascular bypass" (TEB) for stroke therapy was recently reported. In this technique, a stent is temporarily deployed for instant recanalization. Once sufficient flow is established to maintain vessel patency, the stent is recaptured and withdrawn. We report a second case to further characterize the merits of TEB.

Double-Barrel Technique for Preservation of Aortic Arch Branches During Thoracic Endovascular Aortic Repair

Thoracic endovascular aortic repair (TEVAR) may involve either planned or inadvertent coverage of aortic branch vessels when stent grafts are implanted into the aortic arch. Vital branch vessels may be preserved by surgical debranching techniques or by placement of additional stents to maintain vessel patency. We report our experience with a double-barrel stent technique used to maintain aortic arch branch vessel patency during TEVAR. Seven patients underwent TEVAR using the double-barrel technique, with placement of branch stents into the innominate (n = 3), left common carotid (n = 3), and left subclavian (n = 1) arteries alongside an aortic stent graft. Gore TAG endografts were used in all cases, and either self-expanding stents (n = 6) or balloon-expandable (n = 1) stents were utilized to maintain patency of the arch branch vessels. In three cases the double-barrel stent technique was used to restore patency of an inadvertently covered left common carotid artery. Four planned cases involved endograft deployment proximally into the ascending aorta with placement of an innominate artery stent (n = 3) and coverage of the left subclavian artery with placement of a subclavian artery stent (n = 1). TEVAR using a double-barrel stent was technically successful with maintenance of branch vessel patency and absence of type I endoleak in all seven cases. One case of zone 0 endograft placement with an innominate stent was complicated by a left hemispheric stroke that was attributed to a technical problem with the carotid-carotid bypass. On follow-up of 2-18 months, all double-barrel branch stents and aortic endografts remained patent without endoleak, migration, or loss of device integrity. The double-barrel stent technique maintains aortic branch patency and provides additional stent-graft fixation length during TEVAR to treat aneurysms involving the aortic arch. Moreover, the technique uses commercially available devices and permits complete aortic arch coverage (zone 0) without a sternotomy. Although initial outcomes are encouraging, long-term durability remains unknown.

Successful Emergency Endovascular Treatment for Superior Vena Cava Injury

Superior vena cava (SVC) hemorrhage due to iatrogenic injury is an infrequent but important event. We report the case of a 56-year-old woman with a history of right pneumonectomy for lung cancer with iatrogenic SVC injury and hemorrhage. After unsuccessful attempts at suture repair of the defect, an endovascular approach using a stent graft succeeded in controlling hemorrhage while maintaining vessel patency. To our knowledge, this is the third report of SVC hemorrhage control using this technique, and it supports the experience of other authors that endovascular stenting is an effective means of treating emergent venous hemorrhage.

Innovations in PAD therapy

Innovations in PAD therapy

A Novel, Self-Expanding, Nitinol Stent in Medically Refractory Intracranial Atherosclerotic Stenoses

The purpose of this study was to assess the safety and performance of the Wingspan stent system and Gateway percutaneous transluminal angioplasty balloon catheter in the treatment of high-grade, intracranial atherosclerotic lesions in patients who had failed medical therapy. In this prospective, multicenter, single-arm study, medically refractory patients with a modified Rankin score < or =3 and recurrent symptoms attributable to angiographically demonstrated intracranial stenosis > or =50% in a vessel 2.5 to 4.5 mm in diameter were enrolled. Intracranial lesions were predilated with an undersized Gateway balloon catheter to 80% of the native vessel diameter, followed by deployment of the self-expanding Wingspan stent to facilitate further remodeling of the atherosclerotic plaque and to maintain vessel patency. Neurologic examinations and angiograms were performed at 6 months after the procedure. Among the 45 patients enrolled, the degree of stenosis was reduced from a baseline of 74.9+/-9.8% to 31.9+/-13.6% after stenting and 28+/-23.2% at the 6-month follow-up. The 30-day composite ipsilateral stroke/death rate was 4.5% (2/44); at the 6-month follow-up, the ipsilateral stroke/death rate was 7.0%, the rate for all strokes was 9.7%, and all-cause mortality was 2.3%. Physician-reported follow-up in 43 patients (average of 13 months) conducted outside the study protocol (not adjudicated by the clinical event committee) reported 1 additional ipsilateral stroke. In medically refractory patients with high-grade intracranial atherosclerotic stenoses, a new treatment paradigm involving predilation with an undersized Gateway percutaneous transluminal angioplasty balloon catheter and placement of a self-expanding Wingspan stent system appears to be safe, may facilitate remodeling, and may contribute to favorable angiographic outcomes.

A Percutaneous Technique for Preservation of Arch Branch Patency During Thoracic Endovascular Aortic Repair (TEVAR):Retrograde Catheterization and Stenting

To report a percutaneous endovascular technique to deal with stent-graft encroachment and coverage (partial or total) of the origin of the left common carotid artery (CCA) or the left subclavian artery during thoracic endovascular aortic repair. Percutaneous retrograde puncture of the left CCA was accomplished with guidewire advancement into the ascending aorta and insertion of a 6-F sheath. Balloon angioplasty and deployment of a stent across the origin of the left CCA successfully recanalized the vessel and restored normal antegrade flow and pressure. It was reasoned that the stent would maintain vessel patency by focally displacing the endograft device, preventing partial or total coverage (and obstruction) of the arch branch origin. This technique has been used successfully in 8 patients, 6 involving the left CCA and 2 the left subclavian artery. Two of the patients were lost to follow-up after 6 and 12 months. The other 6 patients have been followed from 10 to 32 months; the stented vessels have remained patent in all. While the "interposition" of a bare metal stent between a thoracic endograft and the aortic wall is theoretically unappealing and potentially detrimental, as the direct interaction between the devices might undermine the integrity of one or both, we have not seen such problems in this limited clinical experience.

Diagnostic approach to inherited bleeding disorders

The appropriate development of hemostasis encompasses a delicate equilibrium between anti- and prothrombotic forces developing during three distinct phases (primary hemostasis, coagulation and fibrinolysis) that are closely linked to each other and precisely regulated to close vessel wounds, promote vascular healing and maintain vessel patency. Imbalance in each of these systems produces either hemorrhagic or thrombotic disorders. Inherited bleeding disorders, caused by quantitative or qualitative alterations of either platelets or plasma proteins involved in blood coagulation and fibrinolysis, may lead to serious and lifelong bleeding conditions, the severity of which is inversely associated with the degree of the underlying defect. Rapid and reliable identification of these pathologies is worthy of focus to allow the adoption of appropriate substitutive or supportive antihemorrhagic therapies. Evaluation of the hemorrhage-prone patient requires careful recording of the medical history, attention to pertinent physical findings and the discretionary use of laboratory resources. Owing to the low diagnostic efficiency of clinical history and examination, an appropriate and reliable laboratory approach, encompassing first- and second-line testing, is essential to screen, diagnose and monitor patients with bleeding diatheses. As both the analytical sensitivity and responsiveness of traditional coagulation assays to different abnormalities differ widely, each laboratory should establish individual guidelines based on field experience and on reagent and instrument characteristics. Emerging evidence indicates that the implementation of global coagulation tests, such as the thrombin generation assay and clot waveform analysis, would provide additional information for clinical decision-making for patients with inherited bleeding disorders.

Animal Models of Thrombosis Help Predict the Human Therapeutic Concentration of PRT54021, a Potent Oral Factor Xa Inhibitor.

Factor Xa (fXa) inhibition has resulted in the emergence of a new class of antithrombotics. Pharmacodynamic monitoring of these agents has proven problematic. The present study was designed todetermine the target concentration of an oral fXa inhibitor required for clinical trials using both thrombin generation assays and three in vivo models anddetermine whether clotting assays such as activated partial thromboplastin time (aPTT) and prothrombin time (PT) would be suitable for monitoring human dosing.PRT54021 (PRT021) is a potent inhibitor of human fXa (Ki=117pM). PRT021 and fondaparinux, an indirect fXa inhibitor, both significantly inhibited TAT and F1.2 generation in human whole blood. Compared to a therapeutic level of fondaparinux (200nM), PRT021 (200nM) was more potent in suppressing both markers. Multiple doses of PRT021 were evaluated in three animal models. The first model, which measured clot accretion on cotton threads placed in rabbit abdominal vena cava, compared inhibition of thrombus mass by PRT021 to that of supratherapeutic doses of enoxaparin (a LMW heparin). The second model compared the ability of PRT021 to maintain vessel patency under arterial flow conditions in FeCl3 induced thrombosis in rat carotid artery to that achieved by enoxaparin or clopidogrel (an antiplatelet agent). The third model investigated inhibition of 111In labeled platelet deposition on dacron grafts and expansion chambers placed in femoral arteriovenous shunts in baboons. PRT021 and enoxaparin were administered as IV infusions and clopidogrel was dosed orally for three days. Ex vivo PT and aPTT were measured in all models. The models encompass stringent criteria of arterial and venous thrombosis and PRT021 produced dose-responsive antithrombotic activity in each of the three models. The efficacy of PRT021 compared favorably to supratherapeutic levels of enoxaparin and clopidogrel. Unlike in the rodent models, efficacy in primates was attained at a much lower dose with minimal prolongation of PT. Species specificity was also demonstrated by in vitro extensions of PT and aPTT in rat, rabbit, baboon and human plasma. A 2X change of PT was attained at concentrations of 8.9, 1.6, 1 and 0.4μM respectively. The data indicate that doses of PRT021 that inhibit thrombin generation in human blood and that provide anticoagulation similar to baboon dosed at 0.49mg/kg may be sufficient to prevent venous thrombosis in humans. Comparative modeling of extents of change in PT to levels of antithrombotic efficacy also leads us to predict that human therapeutic activity for PRT021 may be attained without concurrent changes in ex vivo clotting parameters. The targeted concentration is currently being tested in Phase II trials for its ability to prevent venous thromboembolism in orthopedic surgery patients.Model of ThrombosisAgent, DoseAntithrombotic ActivityaPTT fold changePT fold changeRabbit vena cavaPRT021,3mg/kg76% inhibition2.222.34Rabbit vena cavaEnoxaparin, 1.6mg/kg96% inhibition2.062.01Rat carotidPRT021,19.1mg/kg90% patency1.692.20Rat carotidEnoxaparin, 7.6mg/kg70% patency3.491.19Rat carotidClopidogrel, 3mg/kg/day80% patency1.031.01Baboon arteriovenousPRT021,0.49mg/kg90% inhibition (venous), 32% inhibition (arterial)1.291.17

The safety and efficacy of the StarClose® vascular closure system: The ultrasound substudy of the CLIP study

The StarClose Vascular Closure System (Abbott Vascular, Redwood City, CA) features a nitinol clip that is designed to achieve closure of the femoral arteriotomy access site. The CLIP Study was performed to assess the safety and efficacy of StarClose when compared with standard manual compression following 5-6 French diagnostic or interventional percutaneous procedures. A substudy of this trial was designed to assess the utility of duplex ultrasonography to assess patency of the femoral artery and to determine access site complications (pseudoaneurysm, arteriovenous fistula, hematoma, deep vein thrombosis) in a multicenter prospective trial. This is the report of the duplex ultrasound (DUS) substudy of the CLIP trial. A total of 17 U.S. sites enrolled 596 subjects with 483 subjects randomized at a 2:1 ratio to receive StarClose or manual compression of the arteriotomy after a percutaneous procedure. The study included roll-in (n = 113), diagnostic (n = 208), and interventional (n = 275) arms with a primary safety endpoint of major vascular complications through 30 days and a primary efficacy endpoint of postprocedure time to hemostasis. A substudy of the CLIP interventional arm evaluated DUS images of the closure site at five study sites, targeting 100 subjects at day 30 following hemostasis. The DUS protocol was devised and implemented by an independent vascular ultrasound core laboratory with extensive experience in vascular device trials. DUS inguinal region from 6 cm proximal to 6 cm distal to the arteriotomy puncture was performed. A qualitative examination was performed to determine the presence of iatrogenic vascular injuries: hematoma, pseudoaneurysm (PSA), arteriovenous fistula (AVF), and arterial/venous thrombosis or stenosis using 2-dimensional gray scale, color, and focused Doppler images. DUS of 96 subjects randomized to StarClose (n = 71) and compression (n = 25) were performed and evaluated. There was no evidence of hematoma, PSA, or AVF observed in the StarClose group. No StarClose subjects in the substudy had a PSA or AVF. All patients in the substudy demonstrated patency of the access site artery and vein without thrombosis or stenosis. Finally, in the entire study cohort, no clinically-driven DUS studies demonstrated iatrogenic vascular injury or vessel thrombosis in the StarClose treated patients. DUS, a safe and reliable method for determining the safety and efficacy of access site closure devices, is a reliable, safe, inexpensive and accurate method of assessing vascular access site complications in multicenter trials. In this substudy of the CLIP study, DUS found no statistical difference in access site complications between the StarClose and manual compression groups. Both groups maintained vessel patency without stenosis, thrombosis, hematoma, pseudoaneurysm, or AV fistula.