Catheter-directed thrombolysis reduces post-thrombotic syndrome after DVT

Catheter-directed thrombolysis appeared associated with a persistent risk reduction for post-thrombotic syndrome among patients with extensive proximal deep vein thrombosis, according to follow-up results from a randomized controlled trial.

However, assignment to this therapy did not appear associated with improved quality of life, and further research is needed to determine the optimal endovascular thrombolytic approach for DVT.

“Research into treatment of DVT has focused on the efficacy and safety of anticoagulants to prevent recurrent thrombosis,” Per Morten Sandset, MD, head of hematology research at Oslo University Hospital, and colleagues wrote. “However, little effort has been made to evaluate how to prevent post-thrombotic syndrome — a chronic disorder characterized by swelling, pain, discomfort, varicose veins, skin eczema and induration, and sometimes leg ulcers. Post-thrombotic syndrome is a major determinant of morbidity and health-related quality of life after DVT and is associated with major socioeconomic costs.”

Sandset and colleagues conducted the CaVenT study, which compared a conventional therapeutic approach of compression stockings and anticoagulants to conventional therapy plus additional catheter-directed thrombolysis in patients with extensive proximal DVT.

The 2-year results of the trial showed that the addition of catheter-directed thrombolysis reduced the risk for post-thrombotic syndrome 14%. However, treatment assignment did not appear to significantly improve quality of life.

The current analysis reports prespecified outcomes of post-thrombotic syndrome at 5 years — assessed with the Villalta score — as well as quality of life at 5 years.

The 5-year follow-up results of the trial included data from 176 patients (catheter-directed thrombolysis, n = 87; standard therapy, n = 89), representing 84% of the initial study population.

Sixty-three patients assigned standard therapy developed post-thrombotic syndrome, compared with 37 patients assigned catheter-directed thrombolysis (71% vs. 43%; P < .0001). This corresponded with an absolute risk reduction of 28% (95% CI, 14-42) and a number needed to treat of four (95% CI, 2-7).

Severe post-thrombotic syndrome — defined as a Villalta score greater than or equal to 15, or the presence of an ulcer — occurred in four patients assigned catheter-directed thrombolysis and one patient assigned standard therapy.

No significant between-group differences occurred regarding quality of life scores. However, independent of treatment, patients who developed post-thrombotic syndrome reported deteriorated quality of life compared with those who did not (P < .0001).

The control arm had a higher dropout rate than the catheter-directed thrombolysis arm (19 patients vs. 6 patients; P = .03). In both arms, 50% of patient dropouts were due to death.

As a study limitation, the researchers acknowledged that no “gold standard” exists for the diagnosis of post-thrombotic syndrome.

“Despite the demonstrated reduction in post-thrombotic syndrome in our study, the best endovascular thrombolytic approach remains unclear,” Sandset and colleagues wrote. “Adjunctive mechanical techniques might have an impact on treatment time, dosages of thrombolytic drug, and possibly the clinical outcome compared with the catheter-directed thrombolysis-only approach.”

The lack of a quality of life improvement may hamper the use of catheter-directed thrombolysis, Chad J. Zack, MD, and Mohamad Alkhouli, MD, both professors of cardiology at Mayo Clinic in Rochester, Minnesota, and Riyaz Bashir, MD, FACC, professor of cardiology at Temple University School of Medicine, wrote in an accompanying editorial.

“Although the trial’s small size restricts adequate evaluation of safety outcomes, major complications in the catheter-directed thrombolysis arm were limited to three major bleeding events,” Zack and colleagues wrote. “It is important to note that all catheter-directed thrombolysis procedures were carried out at one of four specialized centers. Centers with a larger volume of procedures have been associated with improved safety outcomes. It is possible that standardization of treatment protocols minimized adverse events, potentially arguing for the creation of centers of excellence for treating venous thromboembolism, as has been done for the treatment of valvular heart disease and stroke.” – by Cameron Kelsall

Disclosure: The researchers report no relevant financial disclosures. Zack, Alkhouli and Bashir report no relevant financial disclosures.