Avoiding Cardiovascular Complications in Liver Transplantation through Novel Studies (ACCT NOW) in Hypertension

PROJECT SUMMARY One in three liver transplant recipients experiences a cardiovascular event within one year of transplant because of immunosuppression medications and a high prevalence of potentially modifiable cardiovascular risk factors, such as high blood pressure. Hypertension is the foremost modifiable risk factor for cardiovascular events in liver

transplant recipients (LTRs); however, there is insufficient evidence to guide treatment approaches (e.g., blood pressure target level, medication choice, treatment timing) of hypertension in LTRs that maximize cardiovascular benefit while minimizing potential harms to the liver, kidney, and brain. Intensive blood pressure lowering is

indicated in high cardiovascular risk populations and cardiac biomarker levels can aid in matching blood pressure-lowering therapy to those most likely to benefit; however, in LTRs, concerns about the harms and tolerability of intensive blood pressure control limit aggressive blood pressure targets in clinical practice,

highlighting a need for a precision medicine approach to hypertension management in LTRs informed by cardiac biomarker levels. To address these knowledge gaps for clinical practice, we will conduct a prospective, multicenter, cohort study of 1,268 LTRs and measure 7-day home blood pressure, cardiac biomarker levels,

cardiovascular events, liver graft function, renal function, and cognitive function over two years with outcomes up to five years post-transplant. We will determine the net clinical benefit of blood pressure-lowering on target organs in LTRs (Aim 1), determine whether cardiac biomarker levels can improve stratification of cardiovascular

risk among LTRs with elevated blood pressure or hypertension (Aim 2), and identify optimal treatment approaches in hypertension post-liver transplant that lower blood pressure and minimize cardiovascular events (Aim 3). Our central hypothesis is that elevated cardiac biomarker levels can inform optimal treatment

approaches for hypertension in LTRs that maximize cardiovascular benefit and minimize harms to the liver, kidney, and brain. We will leverage the existing infrastructure of the Avoiding Cardiovascular Complications in Liver Transplantation through Novel Studies (ACCT NOW) consortium, comprised of multidisciplinary clinicians

and researchers across six U.S. transplant centers, whose long-term goal is to establish evidence-based guidelines for cardiovascular disease prevention in liver transplantation. The current aims, when achieved, will (1) define hypertension treatment approaches that are most likely to effectively reduce blood pressure, a key

modifiable risk factor for cardiovascular events, without causing harm in LTRs, (2) delineate the role of cardiac biomarkers to guide these treatment decisions, and (3) identify which LTRs are most likely to benefit from intensive blood pressure lowering to reduce cardiovascular risk. These data are essential for design of a future

randomized type II hybrid intervention trial that will test biomarker-based hypertension management strategies in liver transplant recipients and support the first evidence-based guidance for managing hypertension after liver transplantation.