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 = .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.