Incidence and predictors of recurrent venous thromboembolism after isolated distal deep vein thrombosis: a <i>post-hoc</i> analysis of the RIDTS trial

Contemporary data on recurrent venous thromboembolism (VTE) after anticoagulation for isolated distal deep vein thrombosis (IDDVT) are limited. This post-hoc analysis of the Rivaroxaban for the treatment of symptomatic Isolated Distal deep vein ThrombosiS (RIDTS) trial-a randomized, double-blind trial comparing 6 vs. 12 weeks of rivaroxaban in patients with IDDVT without cancer- evaluated the short- and long-term incidence and predictors of post-treatment recurrent VTE. Sixty-one of 398 (15.3%) participants experienced recurrent VTE (median time from anticoagulation cessation, 6.2 months): 47 (77%) events were recurrent IDDVT, and 14 (23%) proximal DVT (nine, 14.8%) or symptomatic pulmonary embolism (five, 8.2%); 39 (63.9%) recurrences were symptomatic and 22 (36.1%) asymptomatic. During follow-up, six (1.5%) participants died (no deaths attributable to pulmonary embolism). The 6- and 24-month incidence rates per 100/person-years of any recurrence were: 15.8 (95% confidence interval [CI], 11.0-22.7) and 10.0 (95%CI, 7.8-12.9), respectively. The corresponding values were: 24.1 (95%CI, 16.1-36.4) and 15.7 (95%CI, 11.8-20.9) after unprovoked IDDVT; and 6.8 (95%CI, 3.0-15.1) and 4.5 (95%CI, 2.7-7.7) after provoked IDDVT. Recurrence rates were higher in patients who received 6 vs. 12 weeks of rivaroxaban, especially early after discontinuation (24.4 [95%CI, 16.1-37.0] and 7.5 [95%CI, 3.6-15.7] during the first 6 months, respectively). In multivariable analysis, shorter duration of anticoagulation (hazard ratio [HR], 1.8; 95%CI, 1.1-3.0), diabetes (HR, 2.5; 95%CI, 1.1-5.3) and unprovoked IDDVT (HR, 3.2; 95%CI, 1.7-5.7) were associated with increased posttreatment recurrence risk. In patients with IDDVT and without cancer completing 6-to-12 weeks of anticoagulation, recurrent VTE was not infrequent in selected subgroups; these data may inform improved risk stratification and individualized management.