(CVP001) ANTICOAGULATION POST-PULMONARY ENDARTERECTOMY: A RETROSPECTIVE COHORT STUDY

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a devastating disease, but is treatable with pulmonary endarterectomy (PEA) and life-long anticoagulation (AC). Direct oral anticoagulants (DOACs) are largely replacing vitamin K antagonists (VKAs) as first line AC for many indications, but data is limited in the post-PEA setting. We aimed to compare DOACs to VKAs in CTEPH post-PEA patients for recurrent VTE, composite major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) (ISTH definitions), MB, CRNMB, overall mortality, and initiation of targeted pulmonary hypertension therapy (TPHT).

METHODS AND RESULTS: This was a REB approved single center, retrospective, cohort study of CTEPH patients who underwent PEA between Jan 2005 to February 2022 with long-term follow up at our institution. Patient identification and clinical data were obtained from an institutional CTEPH database, and the electronic patient chart. Patients were followed from post-PEA discharge to last known follow up, or until discontinuation of oral AC. Outcomes by AC group were calculated as events per 100 person-years and compared as rate ratios with 95% confidence intervals (CI) using the Mid-P exact test.

The cohort included 336 individuals, of which 171 received DOACs and 195 received VKAs at some point, with total follow-up of 1095 patient years (Table 1). The mean age was 58.15 years, and 50% were female. There was a statistically significant higher rate of recurrent VTE with DOACs compared to VKAs (rate ratio 2.62 (95% CI 1.06 to 6.50)) (Table 2). There were no differences in composite MB and CRNMB, MB, CRNMB, death, or initiation of TPHT between the two groups.

Conclusion: Our study comparing DOACs to VKAs in CTEPH patients post-PEA found a higher rate of recurrent VTE on DOACs, but no difference in bleeding, initiation of TPHT or mortality. Further studies are needed to assess the safety and efficacy of DOACS in CTEPH.

Lay Abstract Content: Purpose of the research: A minor proportion of patients who suffer from pulmonary embolism (blood clots in arteries supplying the lungs) will develop a condition called chronic thromboembolic pulmonary hypertension (CTEPH). This is a serious complication that can cause shortness of breath, fatigue, heart failure and death if untreated. Fortunately, it is treatable with a form of extensive surgery where the clots are removed from the lung vasculature (a pulmonary endarterectomy: PEA) followed by treatment with blood thinners (anticoagulants) for life to prevent the recurrence of blood clots. It is unclear what type of anticoagulants are best suited for treating these patients’ long term. Compared to traditional anticoagulants, vitamin K antagonists (VKAs), the newer anticoagulants (Direct Oral Anticoagulants: DOACs) are prescribed at fixed doses without requirement for routine laboratory monitoring of effect, and have a lower risk of bleeding, but minimal data is available for their in this demographic. We aim to identify if DOACs are as efficacious and safe in reducing blood clots compared to Warfarin.

Relevance of the research: While DOACs are more convenient and safer than VKAs, there is little data to describe their effectiveness and safety specifically post-PEA. This study will help us assess the effectiveness and safety of DOACs compared to VKAs in this demographic. The data obtained from the study will help guide clinician and patient shared decision making regarding appropriate anticoagulation choices.

General approach: We manually identified and reviewed charts of patients who underwent a pulmonary endarterectomy at the Toronto General Hospital over the past 17 years. We then compared the outcomes based on the type of anticoagulation patients received (DOAC or VKA), including death, bleeding, recurrence of blood clots, and the need for additional CTEPH directed therapies. After applying statistical techniques we identified that there was a difference between the groups showing higher rates of recurrent blood clots in the veins of the lungs and lower extremities with DOACs compared to VKAs.