Benefits of Achieving Robust Clot Resolution in VTE Patients...

Benefits of Achieving Robust Clot Resolution in VTE Patients While Balancing Lower Risk of Adverse Events By Michael J. Cerminaro , Brian G. Firth

2020-10-13

How Advanced Catheter-Directed Therapies May Help Improve Outcomes While Reducing the Incidence of Post-PE Syndrome (CTED/CTEPH) and Post-Thrombotic Syndrome (PTS) in the Treatment of VTE Patients.

VENOUS THROMBOEMBOLISM (VTE) is a vascular condition that affects about 10 million patients worldwide each year. Deep vein thrombosis (DVT) most often forms in the deep veins of the legs, groin, or arms. If they break loose, they can travel to the pulmonary arteries in the lungs and result in a pulmonary embolism (PE), with potentially fatal outcomes. Together, DVT and PE are known as VTE.

VTE is a leading cause of death and disability worldwide. Venous clots affect up to 900,000 people a year in the United States alone, and about 100,000 of those patients die. VTE is the third leading cause of cardiovascular mortality and morbidity after coronary artery disease and stroke.1 It is also the leading cause of death in hospitalized patients. Also, VTE contributes to a yearly economic burden of $7–10 billion in the United States alone.2

Traditionally, the majority of VTE patients have been treated with anticoagulation alone.

However, up to 50% of patients who present with lower extremity DVT develop post-thrombotic syndrome (PTS), despite being treated with anticoagulation therapy and compression therapy. Of patients with PE who are treated with anticoagulation therapy, 35–50% go on to develop some form of functional limitation (post-PE syndrome).3, 4

The Role of Catheter-Directed Interventions Clinical data from several large studies suggest the use of catheter-directed interventions for the treatment of acute proximal DVT may help reduce acute symptoms and improve quality of life. Likewise, several different catheter-directed thrombolysis (CDT) and percutaneous mechanical thrombectomy trials have shown prompt improvement in right ventricular function when treating patients with massive and/or submassive PE. Two important goals of catheter-directed interventions for DVT should be to prevent or reduce the likelihood of developing PTS and to improve quality of life.5 The primary goal of catheter-directed therapy of massive/submassive PE is to relieve right heart strain as quickly as possible and restore the patient to a hemodynamically stable condition. However, a long-term goal should also be to reduce the incidence of post-PE syndrome, chronic thromboembolic disease (CTED), and chronic thromboembolic pulmonary hypertension (CTEPH).

The mainstay of treatment for patients with VTE is anticoagulation.6 The purpose of anticoagulation is the prevention of recurrent thrombosis, embolization, and death. Advanced therapies like systemic thrombolytics (which may involve up to 100mg of r-tPA) are effective at lysing the clot but carry up to a 30% risk of bleeding, including a 2–3% risk of intracranial hemorrhage. This has led to a quest to identify treatments that carry a much better risk-benefit ratio directed more locally at the culprit thrombus without the risks of severe bleeding complications. Two broad approaches have evolved to resolve the clot: localized CDT and mechanical extraction of the clot (mechanical thrombectomy). Each approach has its own pros and cons that merit discussion.

CDT—with localized administration of lower doses of thrombolytics through catheters with multiple side holes—has been used for some time with variable success. This approach is not appropriate for patients who present with a high risk of bleeding. One variation on this CDT approach has been the addition of low-frequency ultrasound (USAT), which is purported to enhance clot lysis, based on bench-top data. When used to administer r-tPA—in a dosage of 24 mg over 12–24 hours—to patients with massive and submassive PE, it resulted in improvement in right heart function. However, the therapy was complicated by a 10% incidence of major bleed-ing.7 While this is substantially lower than the systemic therapy bleeding risk of up to 30% and intracranial hemorrhage risk of up to 3%, this still poses unacceptable risks. When lower doses of r-tPA were administered with USAT, there was still benefit in terms of reduction in right ventricular to left ventricular (RV/LV) ratio, but the reduction in clot burden was progressively lower as the r-tPA dose was decreased, in a stepwise fashion.8 USAT has been shown to be safe for the treatment of DVT.9,10 However, its benefit over standard, multi-side-hole CDT therapy remains controversial.

A retrospective study of 83 patients failed to demonstrate a clinical benefit of USAT over standard