Optimal length of oral anticoagulant treatment for maximum benefit within 5 years after discontinuation of oral anticoagulants in patients with acute pulmonary embolism who require secondary thromboprophylaxis

BACKGROUND: Extended oral anticoagulant (OA) use is recommended in patients with acute pulmonary embolism (PE) who require secondary thromboprophylaxis. Nevertheless, the optimal length of OA use for the maximum long-term benefit in this patient population has been undefined to date. METHODS: A retrospective study was performed to explore the role of different length of overall OA use (group 1 (≥1 year of OA use and <2 years of OA use), group 2 (≥2 years of OA use and <3 years of OA use), group 3 (≥ 3 years of OA use)) in outcomes within 5 years after OA discontinuation in patients with acute PE, who required secondary thromboprophylaxis. The primary outcome was mortality rates. The secondary outcomes comprised venous thromboembolism (VTE) recurrence, major bleeding during OA use and net clinical benefit. Net clinical benefit was defined as the composite of recurrent VTE and major bleeding. RESULTS: For a total of 385 patients in group 1 (n=220), group 2 (n=110) and group 3 (n=55), the PE-related mortality in group 1 was higher than that in group 2 (p=0.034) and 3 (p=0.040), respectively, whereas were similar between groups 2 and 3 (p=1.000). The net clinical benefit in group 1 was less than that in group 2 (p=0.024), whereas similar with that in group 3 (p=0.526). The net clinical benefit was comparable between groups 2 and 3 (p=0.716). The length of OA use was positively associated with major bleeding (HR, 2.510 (0.293 to 3.485), p=0.001), whereas negatively associated with PE-related mortality (HR, 0.668 (0.196 to 2.832), p=0.025) and VTE recurrence (HR, 0.694 (0.174 to 2.300), p=0.036), respectively. The sensitivity and specificity of the length of OA use for the tendency of PE-related mortality was 70.2% and 46.2%, respectively. The area under the curve (AUC) was 0.654 (0.514 to 0.793) (p=0.029). The sensitivity and specificity of the length of OA use for the tendency of net clinical benefit was 86.8% and 64.3%, respectively. The AUC was 0.628 (0.565 to 0.690) (p<0.001) CONCLUSIONS: For patients with acute PE who require secondary thromboprophylaxis, 2 to 3 years (30 months preferred) of overall OA use after a diagnosis of acute PE could be an optimal length to achieve maximum benefit within 5 years after OA discontinuation.