Sex, age and normal post‐anticoagulation D‐dimer as risk factors for recurrence after idiopathic venous thromboembolism in the Prolong study extension

Background: The PROLONG randomized study showed that patients with an abnormal D‐dimer after anticoagulation suspension for a first unprovoked episode of venous thromboembolism (VTE) benefited from anticoagulation resumption. Patients with normal D‐dimer after anticoagulation suspension had a low recurrence rate (4.4% patient–years) but their anticoagulation optimal duration remained uncertain. Objectives: To assess whether sex and age, in combination with normal D‐dimer, are risk factors for VTE recurrence in patients enrolled in the PROLONG study extended follow‐up. Methods: D‐dimer was measured at 1 month after anticoagulation suspension. Patients with a normal D‐dimer did not resume anticoagulants, whereas patients with an abnormal D‐dimer were randomized either to resume or not anticoagulants. Primary outcome was recurrent VTE. Results: After excluding patients resuming anticoagulants for abnormal D‐dimer, recurrences were higher in males than females [7.4% patient‐years – 47/639 vs. 4.3% patient‐years – 27/626; hazard ratio (HR) = 1.7; P = 0.027] and in patients aged 65 or older than in younger patients (8.4% patient‐years – 50/598 vs. 3.6% patient‐years – 24/667; HR = 2.1; P = 0.003). In patients with normal D‐dimer and younger than 65, recurrences were higher in males than in females (5.1% vs. 0.4% patient–years; adjusted HR = 10.6; P = 0.023) and both females and males aged 65 years or older had more recurrences (6.6% and 8.1% patient‐years, respectively, adjusted HR: 16.0; P = 0.008 and 16.0; P = 0.008, respectively) than females younger than 65. Conclusions: In patients with idiopathic VTE and a normal D‐dimer at 1 month after anticoagulation suspension, females younger than 65 had a very low risk of recurrence.