What is the approach to preoperative induction of immunosuppressive agents in heart transplant patients?

From the Guidelines

The preoperative induction of immunosuppression in heart transplant patients should typically involve administering agents such as intravenous methylprednisolone, basiliximab, or anti-thymocyte globulin (ATG) before or during the transplant procedure to prevent early rejection, as supported by recent clinical practices 1.

Approach to Induction Therapy

The approach to preoperative induction of immunosuppressive agents in heart transplant patients involves careful consideration of the patient's immunological risk profile.

• For patients at high risk of rejection, more potent induction therapies such as ATG may be preferred 1.
• For lower-risk patients, IL-2 receptor antagonists like basiliximab may be sufficient 1.
• The use of mycophenolate mofetil preoperatively is also considered in some protocols.

Agents Used in Induction Therapy

• Intravenous methylprednisolone: Given immediately before surgery at doses of 500-1000 mg 1.
• Basiliximab: Administered on the day of transplantation and again on postoperative day 4 at a dose of 20 mg IV 1.
• Anti-thymocyte globulin (ATG): Used at 1.5 mg/kg/day for 3-5 days, starting during or immediately after surgery 1.
• Mycophenolate mofetil: Administered preoperatively at a dose of 1000 mg orally or IV in some centers.

Rationale for Induction Therapy

Induction therapy is crucial for depleting or inhibiting T-cells responsible for acute rejection while the maintenance immunosuppression regimen is being established. It is particularly important for sensitized patients with pre-formed antibodies or those at high risk for rejection. The choice of induction agent and regimen should be tailored to the individual patient's risk profile to balance efficacy with the risk of adverse effects.

From the Research

Preoperative Induction of Immunosuppressive Agents in Heart Transplant

• The approach to preoperative induction of immunosuppressive agents in heart transplant patients involves the use of various immunosuppressive agents to prevent rejection, as seen in studies such as 2 and 3.
• Induction therapy has been a subject of controversy in heart transplantation, but recent developments have paved the way for new approaches, including the use of antibodies such as alemtuzumab, as discussed in 3.
• The selection of patients who may benefit from induction therapy is crucial, including those with a high risk of developing cellular or antibody rejection, impaired renal function, or those requiring calcineurin inhibitor-free therapy, as noted in 3.

Types of Immunosuppressive Agents

• Various immunosuppressive agents are used in heart transplantation, including:
  • Basiliximab, as studied in 2
  • Rabbit anti-thymocyte globulin (RATG), as mentioned in 2
  • Alemtuzumab, as discussed in 3
  • Cyclosporine, everolimus, and mycophenolate mofetil, as used in 2 and 4
  • Sirolimus and interleukin-2 receptor antibodies, as introduced in 4

Phases of Immunosuppression

• Current immunosuppressive regimens typically consist of two phases: induction phase and maintenance therapy, as discussed in 5.
• Induction medications are given to decrease the occurrence of early acute rejection, avoid or minimize corticosteroids, and potentially induce long-term favorable immunoregulatory effects, as noted in 5.
• Maintenance therapy is required after all solid-organ transplantations to prevent rejection, as mentioned in 5 and 6.

Importance of Individualized Drug Use

• The optimal immunosuppressive therapy post-transplant is not established, and individualized drug use is crucial to minimize side effects and prevent organ rejection, as discussed in 6.
• Discovering less toxic but more potent new agents is of great importance, and new experimental and clinical studies are needed in this regard, as noted in 6.