Frequency and risk factors for Chronic Thromboembolic Pulmonary Hypertension after a first unprovoked Pulmonary Embolism: results from PADIS-studies

Abstract

<b>Importance:</b> We aimed to determine the frequency and risk factors for chronic thromboembolic pulmonary hypertension (CTEPH) after a first unprovoked pulmonary embolism (PE). <b>Methods:</b> In a randomized trial comparing an additional 18-month warfarin treatment versus placebo after a first unprovoked PE initially treated with vitamin K agonist during 6 months, we applied recommended CTEPH screening strategies through 8-year follow-up to determine cumulative incidence. CTEPH risk factors were estimated using Cox models. Pulmonary vascular obstruction (PVO) and systolic pulmonary arterial pressure (sPAP) at PE diagnosis and at 6 months were studied by receiver operating curves analyses. All CTEPH cases, whether they were incident or prevalent, were adjudicated centrally. <b>Results:</b> During a median follow-up of 8.7 years, 9 CTEPH cases were diagnosed among 371 patients, with a cumulative incidence of 2.8% (95% confidence interval (CI), 0.95-4.64), and of 1.31% (95%CI, 0.01-2.60) after exclusion of 5 cases adjudicated as prevalent. At PE diagnosis, PVO&gt;45% and sPAP&gt;56mmHg were associated with CTEPH hazard ratio (HR) of 33.00 (95%CI 1.64-667.00, p=0.02) and 12.50 (95%CI 2.10-74.80, p&lt;0.01) respectively. Age&gt;65 years, lupus anticoagulant antibodies and non-O blood groups were also predictive of CTEPH. PVO&gt;14% and sPAP&gt;34mmHg at 6-month were associated with CTEPH (HRs 63.90 [95%CI, 3.11-1310,00 p&lt;0.01]and 17.2 [95%CI, 2.75-108, p&lt;0.01] respectively). <b>Conclusion:</b> After a first unprovoked PE, the cumulative incidence of CTEPH was 2.8% during 8-year follow-up. PVO and sPAP at PE diagnosis and at 6 months were the main risk factors of CTEPH.