Mohsen Sharifi

Moderate Pulmonary Embolism Treated With Thrombolysis (from the “MOPETT” Trial)

The role of low-dose thrombolysis in the reduction of pulmonary artery pressure in moderate pulmonary embolism (PE) has not been investigated. Because the lungs are very sensitive to thrombolysis, we postulated that effective and safe thrombolysis might be achieved by a lower dose of tissue plasminogen activator. The purpose of the present study was to evaluate the role of this safe dose thrombolysis in the reduction of pulmonary artery pressure in moderate PE. During a 22-month period, 121 patients with moderate PE were randomized to receive a safe dose of tissue plasminogen activator plus anticoagulation (thrombolysis group [TG], nxa0= 61 patients) or anticoagulation alone (control group [CG], nxa0= 60). The primary end points consisted of pulmonary hypertension and the composite end point of pulmonary hypertension and recurrent PE at 28 months. Pulmonary hypertension and the composite end point developed in 9 of 58 patients (16%) in the TG and 32 of 56 patients (57%) in the CG (p <0.001) and 9 of 58 patients (16%) in the TG and 35 of 56 patients (63%) in the CG (p <0.001), respectively. The secondary end points were total mortality, the duration of hospital stay, bleeding at the index hospitalization, recurrent PE, and the combination of mortality and recurrent PE. The duration of hospitalization was 2.2 ± 0.5 days in the TG and 4.9 ± 0.8 days in the CG (p <0.001). The combination of death plus recurrent PE was 1 (1.6%) in TG and 6 (10%) in the CG (pxa0= 0.0489). No bleeding occurred in any group, and despite a positive trend in favor of a safe dose thrombolysis, no significant difference was noted in the rate of individual outcomes of death and recurrent PE when assessed independently. In conclusion, the results from the present prospective randomized trial suggests that safe dose thrombolysis is safe and effective in the treatment of moderate PE, with a significant immediate reduction in the pulmonary artery pressure that was maintained at 28 months.

Endovenous therapy for deep venous thrombosis: The TORPEDO trial

Objectives. We compared the efficacy and safety of percutaneous endovenous intervention (PEVI) plus anticoagulation with anticoagulation alone in the reduction of venous thromboembolism (VTE) and post‐thrombotic syndrome (PTS) in acute proximal deep venous thrombosis (DVT). Background. Recurrent VTE and PTS are common complications of DVT. There are no randomized trials investigating the efficacy of PEVI in the reduction of the above complications. Methods. Patients with symptomatic proximal DVT were randomized to receive PEVI plus anticoagulation or anticoagulation alone. Anticoagulation consisted of intravenous unfractionated heparin or subcutaneous low‐molecular weight heparin plus warfarin. PEVI consisted of one or more of a combination of thrombectomy, balloon venoplasty, stenting, or local low‐dose thrombolytic therapy. Results. At 6 months follow‐up, recurrent VTE developed in 2 of 88 patients of the PEVI plus anticoagulation group versus 12 of 81of the anticoagulation‐alone group (2.3% vs. 14.8%, P = 0.003). PTS developed in 3 of 88 patients of the PEVI plus anticoagulation Group and 22 of 81 of the anticoagulation‐alone group (3.4% vs. 27.2%, P < 0.001). Conclusions. In patients with symptomatic proximal DVT, PEVI plus anticoagulation may be superior to anticoagulation—alone in the reduction of VTE and PTS at 6 months.

Thrombus Obliteration by Rapid Percutaneous Endovenous Intervention in Deep Venous Occlusion (TORPEDO) Trial: Midterm Results

Purpose To present midterm results from a randomized study comparing the safety and efficacy of percutaneous endovenous intervention (PEVI) + anticoagulation vs. anticoagulation alone in the reduction of venous thromboembolism (VTE) and post-thrombotic syndrome (PTS) in acute symptomatic proximal deep venous thrombosis (DVT). Methods The TORPEDO trial was a randomized study to demonstrate superiority of PEVI in the reduction of the VTE and PTS at 6 months; in that trial, 183 patients (103 men; mean age 61±11 years) with symptomatic proximal DVT were randomized to receive PEVI + anticoagulation (n=91) or anticoagulation alone (n=92). PEVI consisted of one or more of a combination of thrombectomy, balloon venoplasty, stenting, and/or local low-dose thrombolytic therapy. Results At 6 months, recurrent VTE developed in 2.3% of the PEVI + anticoagulation group vs. 14.8% in the anticoagulation only group (p=0.003); PTS developed in 3.4% vs. 27.2% (p<0.001), respectively. At a mean follow-up of 3065 months (range 12–41), 88 patients in the PEVI + anticoagulation group and 81 patients in the anticoagulation only group reached target follow-up. Recurrent VTE developed in 4 (4.5%) of the 88 PEVI + anticoagulation patients vs. 13 (16%) of the 81 patients receiving anticoagulation only (p=0.02). PTS developed in 6 (6.8%) of the PEVI + anticoagulation group vs. 24 (29.6%) of the anticoagulation only group (p<0.001). Conclusion In patients with proximal DVT, PEVI is superior to anticoagulation alone in the reduction of VTE and PTS. This benefit, which appears early in the course of treatment, extends to >2.5 years.

Role of IVC Filters in Endovenous Therapy for Deep Venous Thrombosis: The FILTER-PEVI (Filter Implantation to Lower Thromboembolic Risk in Percutaneous Endovenous Intervention) Trial

ObjectivesThe purpose of this study was to evaluate the necessity of and recommend indications for inferior vena cava (IVC) filter implantation during percutaneous endovenous intervention (PEVI) for deep venous thrombosis (DVT).BackgroundPEVI has emerged as a powerful tool in the management of acute proximal DVT. Instrumentation of extensive fresh thrombus is potentially associated with iatrogenic pulmonary embolism (PE). The true frequency of this complication has not been studied in a randomized fashion. We evaluated IVC filter implantation during PEVI for DVT.MethodsA total of 141 patients with symptomatic proximal DVT undergoing PEVI for symptomatic DVT were randomized to receive an IVC filter (70 patients) or no filter (71 patients; control group). The anticoagulation and PEVI regimen were similar between the two groups. Patients with development of symptoms suggestive of PE underwent objective testing for PE.ResultsPE developed in 1 of the 14 symptomatic patients in the filter group and 8 of the 22 patients in the control group (Pxa0=xa00.048). There was no mortality in any group. Three patients (4.2%) in the control group had transient hemodynamic instability necessitating resuscitory efforts. Predictors of iatrogenic PE were found to be PE at admission; involvement of two or more adjacent venous segments with acute thrombus; inflammatory form of DVT (severe erythema, edema, pain, and induration); and vein diameter ofxa0≥7xa0mm with preserved architecture.ConclusionsIVC filter implantation during PEVI reduces the risk of iatrogenic PE by eightfold without a mortality benefit. A selective approach may be exercised in filter implantation during PEVI.

New oral anticoagulants in the treatment of heparin- Induced thrombocytopenia

BACKGROUNDnHeparin induced thrombocytopenia (HIT) is a potentially catastrophic syndrome with a high incidence of vascular thrombosis. There are little data on the efficacy of new oral anticoagulants (NOAC) in this setting. This study reports on the outcome of patients with HIT, treated with NOAC.nnnMATERIALS AND METHODSnWe retrospectively identified 22 patients with HIT who were treated by our group with a combination of NOAC and a short course of argatroban. These patients were evaluated in a prospective fashion for development of outcomes at a mean follow up of 19±3 months.nnnRESULTSnThere were a total of 5 deep and 2 superficial vein thromboses diagnosed at index hospitalization. No patient developed arterial thrombosis. All patients tolerated NOAC and their platelet count normalized before discharge. At 19 months of follow-up, 6 patients had died of non-thrombotic causes. There was no bleeding, limb loss or recurrent venous thromboembolism in any patient.nnnCONCLUSIONSnIn patients with HIT, a short course of parenteral treatment with argatroban followed by administration of a NOAC is highly safe and effective in prevention of thrombosis and normalization of platelet count. Development of HIT however, portends a poor prognosis independent of vascular thrombosis.

Effect of anticoagulation on endothermal ablation of the great saphenous vein.

BACKGROUNDnA growing number of patients who are on systemic anticoagulation with warfarin require endovenous thermal ablation for reflux disease in the great saphenous vein (GSV). Little is known about the effects of anticoagulation on periprocedural bleeding and long-term closure rates of the treated veins. This study evaluated the effects of uninterrupted anticoagulation in patients undergoing endovenous thermal ablation.nnnMETHODSnIn this prospective observational study, 88 limbs of patients on warfarin (anticoagulation group [AG]) who underwent endovenous thermal ablation for GSV reflux disease were compared with 92 limbs in patients receiving no anticoagulation or antiplatelet agents (control group [CG]). Forty percent of AG patients were also receiving antiplatelet therapy. Periprocedural bleeding and closure rate at 1 year were evaluated.nnnRESULTSnNo major bleeding occurred in either group. Minor bleeding was noted in 8 of 88 procedures in the AG vs 4 of 92 in the CG (P = 0.24); all in patients receiving radiofrequency ablation. Four of the eight minor bleeds in the AG were noted in patients receiving triple therapy with warfarin, aspirin, and clopidogrel or ticlopidine. Triple therapy in the AG was associated with a higher risk of minor bleeding compared with the CG (relative risk, 13.0; 95% confidence interval, 4.10-41.19, P < .001). All treated venous segments remained closed at the 1-year follow-up in both groups.nnnCONCLUSIONSnIn this relatively small, nonrandomized study comparing endovenous thermal ablation in patients with and without warfarin, no differences were found in periprocedural risk of major bleeding or closure rate of the treated venous segments. Minor bleeding was increased in patients receiving triple therapy with warfarin, aspirin, and a thienopyridine who underwent radiofrequency ablation.

Catheter-directed Thrombolysis with Argatroban and tPA for Massive Iliac and Femoropopliteal Vein Thrombosis

PurposeCatheter-directed thrombolysis (CDT) is a highly effective approach in the treatment of deep venous thrombosis (DVT). There are no data on the primary use of CDT with argatroban and tissue plasminogen activator (tPA) in patients without heparin-induced thrombocytopenia (HIT). The aim of this study was to evaluate the efficacy and safety of the combined administration of argatroban and tPA during CDT for massive DVT in patients without HIT.MethodsThirty-three patients with massive symptomatic iliac and femoropopliteal DVT underwent CDT with tPA and argatroban within 28xa0±xa06xa0h of presentation. The dose of tPA was 0.75–1xa0mg/h through the infusion port and that of argatroban at 0.3–1xa0μg/kg/min through the side port of the sheath. The patients were evaluated for the efficacy and safety of CDT and recurrent symptomatic venous thromboembolism (VTE) at a mean follow-up of 22xa0months.ResultsThere was no bleeding or iatrogenic pulmonary embolism with the CDT regimen we used. Grade III lysis (complete resolution of thrombus on venography) was achieved in 30 patients (91xa0%). In 3 patients with additional inferior vena cava filter thrombosis, further thrombectomy of the filter was required. No patient developed recurrent VTE.ConclusionConcomitant administration of argatroban and tPA is a highly safe and effective regimen for CDT for massive DVT.

Low incidence of post-thrombotic syndrome in patients treated with new oral anticoagulants and percutaneous endovenous intervention for lower extremity deep venous thrombosis.

Post-thrombotic syndrome (PTS) is a common complication of deep venous thrombosis (DVT) of the iliofemoral venous system leading to significant morbidity and high health care costs. It has been recently shown that percutaneous endovenous intervention (PEVI) can effectively reduce the incidence of PTS. The role of new oral anticoagulants (NOACs) in combination with PEVI in the reduction of PTS has not been previously studied. This report sought to evaluate the role of PEVI plus NOACs in the reduction of PTS in acute symptomatic femoropopliteal and iliac DVT. We studied 127 patients with acute lower extremity DVT who had undergone PEVI plus administration of NOACs. All had received a minimum of 3 months of anticoagulation with a NOAC following PEVI. The mean follow-up was 22±5 months. The patients were evaluated for development of PTS, bleeding, recurrent venous thromboembolism (VTE), duration of hospitalization and mortality. There was no in-hospital bleeding. The mean duration of hospitalization was 46±9 hours. DVT occurred in two patients who had been later switched to warfarin. There were four non-VTE-related deaths. PTS developed in five patients (3%), two of whom were those who had been switched to warfarin. Their mean Villalta score was 6.2±0.9. We conclude that the combination of PEVI plus NOAC and low dose aspirin is associated with a very low rate of PTS with the severity being only mild. This approach leads to very low rates of bleeding and recurrent VTE and promotes early discharge.

Transforming and Simplifying the Treatment of Pulmonary Embolism: “Safe Dose” Thrombolysis Plus New Oral Anticoagulants

BackgroundAdministration of systemic thrombolysis in pulmonary embolism (PE) has been limited to severe forms due to the risk of intracerebral hemorrhage (ICH). There is growing evidence from small studies that low-dose systemic thrombolysis has equal efficacy to standard dose, while eliminating the risk of ICH. Little data exists on the combined use of low-dose systemic thrombolysis and new oral anticoagulants (NOAC). We evaluated the clinical and echocardiographic outcome of patients treated with low or “safe dose” thrombolysis (SDT) and NOAC at intermediate term.MethodsWe retrospectively identified 159 patients with massive and submassive PE who were treated with SDT and NOAC over a 2-year period by our group. They were followed prospectively for PE-related mortality, recurrent PE, bleeding, change in right/left ventricle (RV/LV) size, pulmonary artery systolic pressure (PASP), and clinical improvement at a mean follow-up of 18xa0±xa03xa0months.ResultsAt 6xa0months, the RV/LV size was reduced from 1.29xa0±xa00.28 to 0.89xa0±xa00.03 (pxa0<xa00.001). The PASP dropped from 53.12xa0±xa03.85xa0mmHg to 30.39xa0±xa03.93xa0mmHg (pxa0<xa00.001). There was no ICH or in-hospital major or minor bleeding. At 18xa0months, three patients died of cancer. Recurrent PE developed in one patient who had been later switched to warfarin. The duration of hospitalization was 1.8xa0±xa00.3xa0days.ConclusionWith combination of SDT and NOAC, treatment of massive and submassive PE becomes identical and is transformed from an “anticoagulation first” to a “thrombolysis first” approach, thereby making treatment streamlined, simple, safe and effective, accessible and inexpensive.

Pulseless electrical activity in pulmonary embolism treated with thrombolysis (from the “PEAPETT” study)

OBJECTIVEnPulseless electrical activity (PEA) during cardiac arrest portends a poor prognosis. There is a paucity of data in the use of thrombolytic therapy in PEA and cardiopulmonary arrest due to confirmed pulmonary embolism (PE). We evaluated the outcome of low-dose systemic thrombolysis with tissue plasminogen activator (tPA) in patients presenting with PEA due to PE.nnnMETHODSnDuring a 34-month period, we treated 23 patients with PEA and cardiopulmonary arrest due to confirmed massive PE. All patients received 50 mg of tPA as intravenous push in 1 minute while cardiopulmonary resuscitation was ongoing. The time from initiation of cardiopulmonary resuscitation to administration of tPA was 6.5 ± 2.1 minutes.nnnRESULTSnReturn of spontaneous circulation occurred in 2 to 15 minutes after tPA administration in all but 1 patient. There was no minor or major bleeding despite chest compression. Of the 23 patients, 2 died in the hospital, and at 22 ± 3 months of follow-up, 20 patients (87%) were still alive. The right ventricular/left ventricular ratio and pulmonary artery systolic pressure dropped from 1.79 ± 0.27 and 58.10 ± 7.99 mm Hg on admission to 1.16 ± 0.13 and 40.25 ± 4.33 mm Hg within 48 hours, respectively (P< .001 for both comparisons). There was no recurrent venous thromboembolism or bleeding during hospitalization or at follow-up.nnnCONCLUSIONnRapid administration of 50 mg of tPA is safe and effective in restoration of spontaneous circulation in PEA due to massive PE leading to enhanced survival and significant reduction in pulmonary artery pressures.