Ultrasound-Accelerated Thrombolysis More Effective Than Heparin Alone for Intermediate PE

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An ultrasound-assisted thrombolysis strategy is more effective than heparin alone for reversing right ventricle dilation in patients with acute, intermediate-risk pulmonary embolism and is not associated with increased bleeding complications, according to a small study published online November 13, 2013, ahead of print in Circulation. The results were first presented in March 2013, at the American College of Cardiology/i2 Scientific Session in San Francisco.

For the ULTIMA (ULTrasound Accelerated ThrombolysIs of PulMonAry Embolism) trial, lead author Nils Kucher, MD, of University Hospital Bern (Bern, Switzerland) and colleagues randomized 59 patients with submassive pulmonary embolism to IV heparin plus accelerated ultrasound with an endovascular device (EkoSonic Endovascular System, EKOS, Bothell, WA; n = 30) or heparin alone (n = 29) between November 2010 and January 2013.

The endovascular device incorporates small ultrasound transmitters that cause fibrin strands to thin and loosen and expose plasminogen receptor sites. This results in increased thrombus permeability and thrombolytic penetration. Simultaneously, the ultrasonic pressure waves force the thrombolytic agent (recombinant t-PA) deep into the pulmonary thrombus.

Significant Differences Seen

Overall, the ultrasound-accelerated strategy was superior to anticoagulation with heparin alone in reversing right ventricular dilatation and dysfunction.

At 24 hours, researchers observed a mean right-to-left ventricular dimension (RV/LV) ratio of 0.99±0.17 in the ultrasound-accelerated  group, a significant decrease from 1.28±0.19 at baseline (P < 0.001).  In the anticoagulation group RV/LV ratios were 1.17±0.20 and 1.20±0.14, respectively (P = 0.31). The mean decrease in RV/LV ratio from baseline to 24 hours was 0.30±0.20 in the ultrasound-accelerated group vs.

0.03±0.16 in the heparin group (P < 0.001).

Additionally, invasive hemodynamic measurements at 18 ± 3 hours post- ultrasound-accelerated thrombolysis confirmed reduced pulmonary artery pressure and increased cardiac index.

Safety assessments indicated no hemodynamic decompensation or recurrent venous thromboembolism in patients at 90 days.  One death occurred in the heparin group and there were no cases of major bleeding. Minor bleeding was seen in 4 patients (3 in the ultrasound-accelerated thrombolysis group and 1 in the heparin group; P = 0.61), with no incidence of recurrent venous thromboembolism.

In conclusion, wrote the study authors, “in PE patients at intermediate risk of death, a standardized USAT regimen was superior to anticoagulation with heparin alone in reversing right ventricular dilatation at 24 hours, without an increase in bleeding complications.” 

Verification Needed

In a telephone interview with TCTMD, Barry T. Katzen, MD, of the Baptist Cardiac & Vascular Institute (Miami, FL), said that while the current standard of practice in this acute, intermediate-risk population is IV anticoagulation, this study will “add to the body of evidence that ultrasound-accelerated thrombolysis benefits this subset of patients.”

The study endpoint of the RV/LV ratio, however, is a surrogate for clinical benefits, specifically decreased morbidity and mortality over time, said Dr. Katzen. Consequently, this research needs to be followed by larger studies that document these clinical outcomes.  While the study found a statistically significant RV/LV ratio benefit of the ultrasound-accelerated strategy, this did not impact mortality during the short study duration, he explained.    

In their paper, Dr. Kucher and colleagues acknowledge that the study was “too small to draw firm conclusions about the clinical efficacy and safety of [ultrasound-accelerated thrombolysis] in comparison with anticoagulation alone.”  They also note that study participants were hemodynamically stable, and “it remains unclear whether [ ultrasound-accelerated thrombolysis] with intrapulmonary r-tPA bolus is effective and safe in unstable PE patients at high risk of death from right ventricular failure.” 

The researchers also note that the long-term benefits of early hemodynamic improvement after reperfusion in patients with acute pulmonary embolism are not well established. “Although evidence from randomized trials is lacking, it is reasonable to suggest that a reperfusion strategy with early improvement in hemodynamic parameters may potentially reduce the incidence of chronic pulmonary hypertension, the main long-term complication of acute PE,” they write.

The study findings and an increasing number of clinicians are finding that pulmonary embolism patients with increased RV/LV ratio experience a clinical benefit with ultrasound-accelerated thrombolysis. Nevertheless, the procedure is invasive and must be performed in a facility by skilled interventionalists who have the resources to place lines in the pulmonary artery, concluded Dr. Katzen.

Study Details

Patients had a mean age of 63±14 years and 53% were female. Participants had a RV/LV ratio of 1 or higher. The ultrasound-accelerated thrombolysis regimen consisted of 10-20 mg rt-PA over 15 hours per treated lung.  Unfractionated heparin was given via intravenous bolus of 80 IU/Kg, followed by an infusion of 18 IU/kg/h.  The bolus was omitted in individuals who were already receiving anticoagulation therapy at time of randomization.

 


Source:
Kucher N, Boekstegers P, Muller O, et al. Randomized controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2013; Epub ahead of print.

 

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Ultrasound-Accelerated Thrombolysis More Effective Than Heparin Alone for Intermediate PE

An ultrasound-assisted thrombolysis strategy is more effective than heparin alone for reversing right ventricle dilation in patients with acute, intermediate-risk pulmonary embolism and is not associated with increased bleeding complications, according to
Disclosures
  • Dr. Kucher is a consultant for EKOS Corp and has received honoraria from Sanofi-Aventis, Boehringer Ingelheim, Pfizer, Bristol Myers Squib and Bayer.
  • Dr. Katzen reports no relevant conflicts of interest.

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