Thrombotic events with proliferation signal inhibitor‒based immunosuppression in cardiac transplantation

https://doi.org/10.1016/j.healun.2019.01.004Get rights and content

BACKGROUND

Some literature exists potentially linking proliferation signal inhibitors (PSIs) to venous thromboembolism (VTE). We sought to determine the impact of PSIs on development of VTE in heart transplant (HT) patients while controlling for other risk factors.

METHODS

The incidence and predisposing factors of VTE were analyzed in this retrospective review of patients >18 years who underwent HT January 2000 to October 2016. Re-transplants, multiorgan transplants, or patients that expired within 30 days post-HT were excluded. VTE incidence rates are reported as number of events per 100 person-years. Cox proportional hazards models were used to assess the relationship between PSI exposure (time-varying covariate) and VTE.

RESULTS

Of 561 HT recipients, 112 received PSIs, started a median of 1.5 years post-HT. There were 102 total VTE events: 78 in PSI-naive patients during 2,547 patient-years (3.0 events per 100 person-years) vs 24 in PSI-exposed patients during 544 patient-years (4.4 events per 100 person-years). Cox proportional hazards models with PSI exposure as a time-varying covariate indicated the increased risk was statistically significant (unadjusted hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.31 to 3.49, p = 0.002). A VTE history was significantly associated with increased risk of VTE post-HT (HR 1.58, 95% CI 1.07 to 2.35, p = 0.022); however, the risk remained significant when adjusting for potential confounders, including previous VTE (HR 2.0, 95% CI 1.18 to 3.38, p = 0.010).

CONCLUSIONS

Exposure to PSIs is associated with a significant increase in risk for VTE even when controlling for other risk factors. When considering the use of PSI-based immunosuppression after HT, the risk of VTE over time should be weighed against the potential benefit.

Section snippets

Setting and design of the study

We performed a single-center, retrospective analysis of all patients aged ≥18 years of age who underwent HT at the University of Pittsburgh Medical Center (UPMC) from January 1, 2000 to October 2, 2016. The institutional review board at the UPMC approved the study protocol. Patient exclusions included re-transplant, multiple-organ transplant, or death <30 days post-HT. Information was collected retrospectively via chart review from electronic medical records. Clinical data with a potential

Results

A total of 561 HT recipients were included in this study. Sirolimus (n = 107) or everolimus (n = 5) was initiated in 112 patients at a median of about 1.5 years (range 24 to 4,403 days) post-HT for renal dysfunction (n = 52), CAV (n = 26), intolerance to current IS (n = 18), malignancy (n = 9), or to augment IS in the setting of rejection (n = 7). None of the other subjects (n = 449) were exposed to a PSI and thus are considered PSI-naive. Baseline demographic data are summarized in Tables 1

Discussion

In this study we have investigated PSI use and its association with thrombotic events in 561 HT recipients. Our results show a higher incidence of thrombotic events in HT recipients exposed to a PSI compared with PSI-naive patients, with an incidence rate of 4.4 episodes per 100 person-years in PSI-exposed patients vs 3.0 episodes per 100 person-years in PSI-naive patients. Incidence remained significantly increased when adjusted for potential confounders. There was also a trend toward higher

Disclosure statement

J.T. has been a speaker for CareDx and HeartWare/Medtronic, and a consultant and/or advisory board member for Abiomed, CareDx, EcroR1, HeartWare/Medtronic, and Thoratec/Abbott. M.S. has been a speaker for CareDx. The remaining authors have no conflicts of interest to disclose.

This work was presented in part at the 38th Annual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation, April 2018, Nice, France.

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