Letter to the Editor regarding ‘Relationships between the use of pharmacomechanical catheter-directed thrombolysis,sonographic findings,and clinical outcomes in patients with acute proximal DVT: Results from the ATTRACT Multicenter Randomized Trial’

We read with great interest the study of Weinberg and colleagues, a duplex ultrasound subgroup analysis of the ATTRACT trial, which for the first time allows for evaluation of the technical procedural success of the study.^1,2 The underlying aim of the ATTRACT trial was to test the open vein hypothesis of deep vein thrombosis (DVT) by early thrombus removal with pharmacomechanical catheter-directed thrombolysis (PCDT), as previous published data had not enabled a clear evaluation and understanding of the efficacy of thrombus removal.

The authors report that at 1 month, the PCDT arm had less residual thrombus than the control arm: common femoral vein (CFV) (21% PCDT vs 35% control, p < 0.0001), femoral vein (51% PCDT vs 70% control, p < 0.0001), and popliteal vein (61% PCDT vs 74% control, p < 0.0001). ¹ Baseline noncompressibility of the CFV was 31/58 (53%) compared with only 21% at 1 month (12/58). It is unclear why the technical success rate of PCDT for CFV thrombus in this substudy was so low (19/31; 61%). In comparison, a separate study of 191 consecutive patients with acute iliofemoral DVT treated with catheter-directed thrombolysis reported duplex ultrasound patency results of > 90% at 1 month. ³ In the ultrasound substudy, technical success was even lower among patients undergoing PCDT in the femoropopliteal group at 1 month: femoral vein and popliteal vein 23/53 (43%) and 13/48 (27%), respectively. ¹ These results make it difficult to prove the open vein hypothesis when residual thrombus was present in nearly 40% of those with treated iliofemoral DVT and up to 70% of those in the popliteal segment, which has previously been associated with long-term procedural success. ³ The importance of successful early thrombus removal was reinforced by results in Supplemental Table S3, which reported that restoration of CFV compressibility at 1 month was associated with significant reduction in the development of PTS (p = 0.004).

Weinberg and colleagues report that venous valvular reflux appears to play a role in progression to moderate-or-severe PTS. ¹ A threshold of 0.5 s was selected to avoid missing instances of reflux; however, it has been demonstrated that a cut-off of > 1 s for femoropopliteal veins better represents patients with venous disease. ⁴ At 12 months, the proportion of patients with reflux in any vein (85% PCDT vs 91% control, p = 0.35) were similar in both groups. Therefore, the authors conclude that PCDT does not reduce venous valvular reflux. As the technical success of PCDT was low, significant residual thrombus was present in treated iliofemoral and femoropopliteal vein segments, and only 18% of the total study population had ultrasound follow-up at 12 months, we find it difficult to understand how the authors justify this conclusion.

In our assessment, the ATTRACT trial has set a foundation for how future studies on the treatment of acute iliofemoral DVT should be modified to truly address the open vein hypothesis. The heterogeneity of data from trials of endovenous thrombolysis makes even meta-analysis of these outcomes difficult, though it is clear that clinical results are predicated upon successful thrombus removal – as this study again demonstrates. ⁵ The importance of technical procedural success in these studies cannot be overstated – low procedural success leads to a closed vein and worse patient outcomes.