Medication Management of Cardiac Allograft Vasculopathy After Heart Transplantation

Abstract

Cardiac allograft vasculopathy (CAV) is a common complication following heart transplantation (HT), resulting in diminished graft survival. The preferred strategy for preventing CAV is optimal medical management; however, for patients who develop CAV, delaying disease progression through effective medication management is equally important. A review of the literature regarding medication management of CAV was conducted via a search of the MEDLINE database. Studies were included if they were published in English, conducted in humans ≥ 18 years of age or older, and used noninvestigational medications. Immunosuppressive medications such as the antiproliferative mycophenolate, the calcineurin inhibitor tacrolimus, and the proliferation signal inhibitors sirolimus and everolimus have been shown to prevent the development of CAV. Certain cardiovascular medications, such as HMG-CoA reductase inhibitors (statins), gemfibrozil, calcium channel blockers, and angiotensin-converting enzyme inhibitors, have also demonstrated efficacy in preventing this disease process. Prevention of CAV has also been observed with prophylaxis against cytomegalovirus infection and antioxidant medications. Despite being commonly used in HT patients, neither antiplatelet agents nor glycemic control have proved effective at preventing CAV. Only sirolimus has been shown to arrest the progress of existing CAV.

Elevated serum vascular endothelial growth factor and development of cardiac allograft vasculopathy in children

“…4 The use of intravascular ultrasound (IVUS) has evolved as a valuable adjunct to coronary angiography 5 ; however, cardiac catheterization is still required and its use is limited by physician expertise and patient size in the pediatric population. Once CAV is diagnosed, modification of immunosuppression to include proliferation signal inhibitors may slow the progression of CAV, 6 but medical treatment is currently known to reverse CAV. Although the diagnosis of moderate or severe CAV portends a significantly higher risk of graft loss, 7 outcomes of pediatric patients with angiographically mild CAV are variable: graft survival is similar to that seen in those without CAV (stable mild CAV), but, in a subset of patients, mild CAV can be rapidly progressive, necessitating listing for retransplantation.…”

Cardiac allograft vasculopathy: Insights on pathogenesis and therapy

“…Platelets may form microthrombi at sites of immune and nonimmune injury in the coronary endothelium, thus contributing to the development of CAV . Platelet aggregation is also increased in HT patients and has been shown to be associated with adverse cardiac events .…”

“…Depending on the CMV serostatus of the donor and recipient, a strategy of universal prophylaxis or pre‐emptive treatment is recommended to reduce CMV disease . Studies evaluating the direct impact of CMV prophylaxis on CAV outcomes, however, remain limited …”

Recent advances in allograft vasculopathy

“…Allograft vasculopathy (AV) is a major cause of late graft dysfunction following cardiac and possibly pulmonary and renal transplantation (1–3). Despite advances made in controlling acute rejection, little progress has been made in treatment or prevention of AV.…”