Temporal Profile of Catheter-directed Thrombolysis on Post-thrombotic Syndrome Outcomes in Iliofemoral DVT Patients: Post-hoc Analysis of ATTRACT Trial

Introduction: Patients with iliofemoral deep vein thrombosis (IFDVT) may preferentially benefit from catheter-directed thrombolysis/thrombectomy (CDT) to reduce the post-thrombotic syndrome (PTS). Our prior analysis of the full NIH ATTRACT trial cohort demonstrated that the maximal benefit of CDT occurs at the day (D) 4-8 symptom-onset-to-randomization (SOR) timeframe (Circulation 2021; 143:1224-1238). However, the optimal time window for CDT benefit specifically for IFDVT patients has not been determined. Hypothesis: IFDVT patients may have a broader time window and greater magnitude for CDT benefit compared to all-comer DVT patients. Methods: We analyzed the IFDVT subgroup (N=391) of the NIH ATTRACT trial to assess optimal SOR timeframes for improved PTS outcomes (Villalta and VEINES-QoL scores). In a series of sensitivity analyses, IFDVT patients were non-prespecified divided into two (early, late) or three (early, intermediate, late) SOR groups. Mean scores were estimated by a piecewise linear-regression growth-curve model, with adjustment for strata including clinical center and baseline covariates (age, sex, BMI) by intention-to-treat analysis. Results: In the IFDVT patients, sensitivity analyses revealed that CDT significantly and maximally improved PTS outcomes in the intermediate D4-9 SOR [CDT +anticoagulation (AC) vs. AC alone; between-group difference= -2.54 (Villalta), +13.13 (VEINES-QoL), p<0.0001 for each]. However, CDT did not provide a benefit at early SOR ≤D3 and later SOR ≥D10 (p>0.05). Moreover, CDT effects differed across SOR 0-3, 4-9 and 10+ days (Villalta: -0.77, -2.54, -1.98; p=0.027), (VEINES-QoL: -1.89, +13.13, +1.92; p=0.022). Conclusions: CDT maximally improves PTS outcomes for IFDVT patients in the D4-9 timeframe, which is a more selective time window and of greater magnitude of PTS benefit than the full ATTRACT trial cohort. However, CDT does not improve outcomes beyond AC at early D0-3 and late D10+ timeframes. These findings may have practice implications to consider symptom duration to optimize AC and CDT therapies in IFDVT patients. Mechanisms underlying the benefit of AC and CDT on PTS outcomes need further study.