Evidence-based pharmacotherapy for prevention and management of cardiac allograft vasculopathy

Abstract

Cardiac allograft vasculopathy (CAV)-mediated by a heterogeneous myriad of immune and non-immune factors, which contribute to the progressive and diffuse thickening of the arterial allograft's tunica intima in one distinct form of CAV, and the build-up of plaque in another-is a major limiting factor of long-term survival post heart transplantation. Information on the optimal pharmacotherapeutic approaches for the prevention and management of CAV is conflicting, scattered, and inconsistent, with numerous recent studies adding to the literature. In this paper, we present a go-to clinical resource with the most updated and comprehensive information on the topic. Immunosuppressant therapy remains a staple, with mTOR inhibitors and mycophenolate mofetil (MMF) showing direct correlation with CAV prevention. More data is now available with calcineurin inhibitor (CNI) minimizing or sparing regimens. More novel approaches are being investigated for the roles of monoclonal antibodies, anti-thymocyte globulin, and bortezomib in preventing or delaying CAV. On the other hand, statins' established efficacy is attributed to lipid-lowering and lipid-independent immunomodulatory effects, with early initiation associated with improved outcomes. The choice of statin is dependent on drug-drug interactions. Other aiding approaches for the prevention of CAV include antioxidant vitamins, aspirin, vasodilators, folate therapy, and, most pertinently, cytomegalovirus prophylaxis. Larger clinical trials are needed before these options are institutionalised. For management of established CAV, early initiation of augmented immunosuppressive therapies may be effective, as well as CNI conversion to mTOR inhibitors with or without standard MMF and azathioprine therapy. Risk of acute rejection needs to be monitored during conversion. Finally, preclinical investigations highlight novel potential therapies for CAV prevention and attenuation, however robust clinical trials are needed to test their efficacy and safety.

Keywords: Cardiac allograft vasculopathy; Heart transplant; Immunosuppressant; Pharmacotherapy; Statin.