Urokinase, Alteplase, or Reteplase for DVT Thrombolysis?

Abstract & Commentary

Synopsis: This retrospective study determined that catheter-directed thrombolysis was equally effective and safe whether urokinase, alteplase, or reteplase was used, but that costs were substantially less with the newer recombinant drugs.

Source: Grunwald MR, et al. J Vasc Interv Radiol. 2004;15:347-352.

Grunwald and colleagues at johns hopkins Hospital reviewed the experience of their institution with catheter-directed thrombolytic therapy for deep-venous thrombosis (DVT) between 1997 and 2003. During this time, because of changes in their availability, urokinase (UK) was the exclusive agent used for the first 2 years, recombinant tissue plasminogen activator (TPA) was the only agent used for the next 20 months, and either TPA or recombinant plasminogen activator (reteplase, RPA) was used at the discretion of the attending vascular interventional radiologist for the remaining 25 months of the study, except for 3 patients who received UK in 2003.

During the 6 years examined in this study, 74 patients received catheter-directed thrombolytic therapy for DVT in a total of 82 limbs. Age, gender, thrombus location, duration of symptoms, and the use of additional interventional therapies did not differ statistically among the patients who received UK, TPA, or RPA. Success rates per limb (complete or partial thrombolysis) were 97% for UK, 97% for TPA, and 100% for RPA. Major/overall complication rates were 5.3%/10.5%, 3.1%/12.5%, and 8.3%/16.7%, respectively for the 3 thrombolytic agents. None of these findings differed statistically between agents. However, drug costs [median, (25th-75th percentiles)] were $6,577 ($3,144 - $14,212) for UK as compared to $488 ($255- $666) and $1,787 ($1,296-$2,006) for TPA and RPA, respectively. These differences in drug costs were statistically significant, both UK vs TPA (P < 0.001) and UK vs RPA (P < 0.01).

Comment by David J. Pierson, MD

Systemic anticoagulation with unfractionated or low-molecular-weight heparin, followed by coumadin, is the traditional management for DVT. Although this approach prevents propagation of existing thrombus, it relies on endogenous mechanisms for clot lysis, which may take long enough for damage to venous valves to occur and predispose the patient to development of post-phlebitic syndrome.1 Whether routine catheter-directed thrombolysis would result in a clinically important reduction in the incidence and severity of post-phlebitic syndrome is still unsettled, although this more aggressive approach is widely used, particularly when thrombosis is extensive or causes severe symptoms.

Within the constraints of its retrospective nature, the sequential use of therapies, and its single-institution data source, this study shows that UK, TPA, and RPA have similar efficacy and safety when used for catheter-directed DVT thrombolysis. Despite this equivalence, however, Grunwald et al pharmacoeconomic analysis revealed that TPA was more than 13 times less expensive than UK, and almost 4 times less expensive than RPA. The use of TPA or RPA in lieu of UK would have resulted in a cost savings of $6,000 or $4,800 per limb, respectively, and the use of TPA in place of RPA would have produced an additional savings of approximately $1,300 per limb. Because only 12 patients received RPA during the period reviewed by Grunwald et al, this last distinction should be viewed as speculative.

Reference

1. Prandoni P, et al. Ann Intern Med. 1996;125:1-7.

David J. Pierson, MD, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, is Editor of CriticalCare Alert.