Increased Risk of Venous Thromboembolism With Everolimus-Based Immunosuppression in Lung Transplant Recipients: A Case-Controlled Study.

Background: Everolimus (EVR) is used in lung transplant recipients (LTxR) for its renal sparing, anti-fibrotic and anti-cancer effects. Sirolimus, the parent compound of EVR, is associated with an increased risk of venous thromboembolism (VTE) in LTxR. We aimed to determine if EVR increased VTE risk in LTxR. Methods: We performed a retrospective, case-control study of LTxR who received EVR at our center. Controls were matched with LTxR on EVR based on time post-LTx and transplant indication. The primary outcome was the proportion of LTxR with VTE [deep venous thrombosis (DVT), pulmonary embolism (PE) or stroke]. Equal time periods (from time of EVR initiation) were assessed for each LTxR on EVR and accompanying control. LTxR receiving warfarin, or with a history of VTE or myocardial infarction were excluded. Fisher's exact and the t tests were used for categorical and continuous variables, respectively. Results: 55 EVR LTxR and 55 controls were included. The mean time evaluated for VTE was 588 ± 402 days for each LTxR. There was a higher proportion VTE in the EVR group [9 (16%) vs. 1 (2%), p=0.02].Table: No Caption available.F=female, M=male, ILD=interstitial lung disease, A1A=alpha-1 antitrypsin deficiency, COPD=chronic obstructive pulmonary disease, UE=upper extremity, LE=lower extremity There was no significant difference in age, gender or LTx type (single vs. double) between groups; however, there were more hospitalizations in the EVR group (1.4 ± 1.5 vs. 0.8 ± 1.4 per LTxR, p=0.05). Three VTE events were intravenous line-associated (all UE DVTs in the EVR group). None of the LTxR with VTE had a surgery requiring hospitalization in 90 days preceding their VTE. Conclusion: EVR was associated with a higher risk of VTE in LTxR in this analysis. EVR may trigger VTE via a class effect of sirolimus and EVR on plasminogen activator inhibitor-1 expression. A more robust analysis, which controls for co-founders, is required to confirm these findings. DISCLOSURES:Schoeppler, K.: Other, Novartis, Grant funds. Zamora, M.: Other, Novartis, Grant Funds.