Frequency and predictors for chronic thromboembolic pulmonary hypertension after a first unprovoked pulmonary embolism: Results from PADIS studies

J Thromb Haemost. 2022 Dec;20(12):2850-2861. doi: 10.1111/jth.15866. Epub 2022 Sep 25.

Abstract

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication of a pulmonary embolism (PE) whose incidence and predictors are not precisely determined.

Objective: To determine the frequency and predictors for CTEPH after a first unprovoked PE.

Patients/methods: In a randomized trial comparing an additional 18-month warfarin versus placebo in patients after a first unprovoked PE initially treated with vitamin K antagonist for 6 months, we applied recommended CTEPH screening strategies through an 8-year follow-up to determine cumulative incidence of CTEPH. CTEPH predictors were estimated using Cox models. Pulmonary vascular obstruction (PVO) and systolic pulmonary arterial pressure (sPAP) at PE diagnosis and 6 months were studied by receiver operating curves analysis. All CTEPH cases and whether they were incident or prevalent were adjudicated.

Results: During a median follow-up of 8.7 years, nine 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 five cases adjudicated as prevalent. At PE diagnosis, PVO > 45% and sPAP > 56 mmHg were associated with CTEPH with a hazard ratio (HR) of 33.00 (95% CI 1.64-667.00, p = .02) and 12.50 (95% CI 2.10-74.80, p < .01), respectively. Age > 65 years, lupus anticoagulant antibodies and non-O blood groups were also predictive of CTEPH. PVO > 14% and sPAP > 34 mmHg at 6 months were associated with CTEPH (HR 63.90 [95% CI 3.11-1310.00, p < .01]and HR 17.2 [95% CI 2.75-108, p < .01]).

Conclusion: After a first unprovoked PE, CTEPH cumulative incidence was 2.8% during an 8-year follow-up. PVO and sPAP at PE diagnosis and at 6 months were the main predictors for CTEPH diagnosis.

Trial registration: ClinicalTrials.gov NCT01894204.

Keywords: clinical studies; incidence; pulmonary embolism; pulmonary hypertension; risk factors.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticoagulants / therapeutic use
  • Chronic Disease
  • Humans
  • Hypertension, Pulmonary* / complications
  • Hypertension, Pulmonary* / diagnosis
  • Hypertension, Pulmonary* / epidemiology
  • Pulmonary Embolism* / complications
  • Pulmonary Embolism* / diagnosis
  • Pulmonary Embolism* / epidemiology
  • Risk Factors

Substances

  • Anticoagulants

Associated data

  • ClinicalTrials.gov/NCT01894204