Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism in the era of direct oral anticoagulants: from the COMMAND VTE Registry-2

Abstract

Abstract Background/Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication after acute pulmonary embolism (PE), and the global need for the diagnosis and prediction of CTEPH is increasing. However, the incidence has not been fully evaluated in the era of direct oral anticoagulants (DOACs). Purpose To clarify the incidence and risk factors for CTEPH after acute PE in the DOAC era. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic venous thromboembolism (VTE) patients among 31 centers in Japan between January 2015 and August 2020. The primary outcome was the incidence of CTEPH in patients with acute PE. The secondary outcome was the adjusted hazard ratio for the prediction of CTEPH development. Results Of the 5197 VTE patients enrolled in the COMMAND VTE Registry-2, 2787 patients had acute PE. After a median 747-day follow-up of 2787 acute PE patients, 48 CTEPH were identified (cumulative incidence 2.4%). The incidence of CTEPH did not significantly differ between the treatments of DOACs (2.3%) and vitamin K antagonists (3.7%). Multivariable Cox regression analysis showed that female sex (adjusted hazard ratio 2.20 [95% CI 1.11 to 4.36], p=.024), right heart load on echocardiography and/or CT (adjusted hazard ratio 12.77 [95% CI 4.51 to 36.19], p<.0001), longer days from onset to diagnosis (each 1 day, adjusted hazard ratio 1.03 [95% CI 1.00 to 1.07], p=.044), lower D-dimer level (each 1 μg/mL, adjusted hazard ratio 0.96, [95% CI 0.93 to 0.99], p=.021) and unprovoked PE (adjusted hazard ratio 2.85, [95% CI 1.32 to 6.17], p=.008) were associated with the development of CTEPH. Conclusions The cumulative incidence of CTEPH after acute PE in the DOAC era was 2.4%. Stratification of the risk of developing CTEPH may be useful for follow-up of acute PE.Cumulative incidence of CTEPH