Are Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARB) recommended for patients with a heart transplant?

From the Guidelines

ACE inhibitors or ARBs are recommended for patients with heart failure, including those with a heart transplant, to reduce morbidity and mortality, as stated in the 2017 ACC/AHA/HFSA focused update 1. The use of ACE inhibitors or ARBs in heart transplant recipients is crucial for managing hypertension and preventing cardiac allograft vasculopathy.

• First-line options include lisinopril or losartan, with dose adjustments based on blood pressure response and kidney function, as recommended in the guidelines 1.
• These medications should be initiated once the patient is hemodynamically stable post-transplant, typically within the first few months.
• Close monitoring of blood pressure, renal function, and potassium levels is essential when starting these medications, with laboratory checks after 1-2 weeks of therapy initiation. The benefits of ACE inhibitors or ARBs in heart transplant patients include:
• Controlling hypertension, which affects 70-90% of recipients
• Reducing left ventricular hypertrophy
• Slowing the progression of cardiac allograft vasculopathy by modulating the renin-angiotensin-aldosterone system
• Providing renoprotective effects, which is important given the nephrotoxicity of calcineurin inhibitors commonly used for immunosuppression 1. However, caution is needed in patients with significant renal dysfunction, and dose adjustments may be necessary when used alongside calcineurin inhibitors.
• The guidelines recommend starting ACE inhibitors at low doses and titrating upward to doses shown to reduce the risk of cardiovascular events in clinical trials 1.
• Similarly, ARBs should be started at low doses and titrated upward, with an attempt to use doses shown to reduce the risk of cardiovascular events in clinical trials 1.

From the Research

Antihypertensive Therapy in Heart Transplant Patients

• The use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) is recommended in heart transplant patients as second-line antihypertensive agents 2, 3.
• ACEIs and ARBs may have a role in preventing long-term complications such as calcineurin-inhibitor induced nephropathy 2.
• Calcium channel blockers (CCBs) are the most commonly and preferred agents in the early posttransplant phase and may have renal protective effects 2, 3.
• The choice of antihypertensive should be based on timing related to transplantation and patient's comorbidities 3.

Comparison of ACEIs and ARBs

• There is no difference in efficacy between ARBs and ACE inhibitors with regard to blood pressure and outcomes of all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease 4.
• ACE inhibitors remain associated with cough and a very low risk of angioedema and fatalities, while ARBs have lower overall withdrawal rates due to adverse events 4.

Considerations for Post-Transplant Hypertension

• Early steroid wean and traditional risk factor modification play an important part in the management of post-heart transplant hypertension 2.
• Novel therapies such as sodium-glucose co-transporter 2 inhibitors (SGLT2i) appear well tolerated and may have benefits in both blood pressure and glycemic control in heart transplant patients, but larger trials are needed 2.
• Antihypertensive therapy should be individually tailored based on other factors, such as time after transplantation, presence of proteinuria/albuminuria, or hyperkalemia 5.