What is the utility of Sildenafil (Phosphodiesterase type 5 inhibitor) in adult congenital heart disease, particularly in patients with pulmonary hypertension?

From the Guidelines

Sildenafil is a beneficial treatment option for adult congenital heart disease patients with pulmonary hypertension, particularly those with Eisenmenger syndrome, as it improves exercise capacity and quality of life. The typical dosing regimen is 20 mg three times daily, though some patients may require dose adjustments based on their clinical response and tolerance 1. Sildenafil works by inhibiting phosphodiesterase type 5 (PDE5), which increases cyclic guanosine monophosphate (cGMP) levels in pulmonary vascular smooth muscle cells, leading to vasodilation in the pulmonary circulation. This mechanism helps reduce pulmonary vascular resistance and pulmonary arterial pressure, which is particularly important in congenital heart disease patients who often develop pulmonary hypertension due to long-standing increased pulmonary blood flow or left heart disease.

Some key points to consider when using sildenafil in this patient population include:

• Accurate diagnosis of Eisenmenger syndrome and exclusion of other potential contributors to right-to-left shunting or pulmonary hypertension are crucial prerequisites to optimize therapy 1
• Combination therapy with other pulmonary vasodilators, such as endothelin receptor antagonists, may be considered for patients with severe pulmonary hypertension or those who don't respond adequately to sildenafil alone 1
• Treatment should be initiated under specialist supervision with regular monitoring of oxygen saturation, blood pressure, and clinical symptoms
• Patients should be aware that sildenafil may cause headaches, flushing, nasal congestion, and hypotension as common side effects, and it should not be combined with nitrates due to the risk of severe hypotension 1

Overall, sildenafil is a valuable treatment option for adult congenital heart disease patients with pulmonary hypertension, and its use should be guided by the most recent and highest quality evidence, such as the 2019 AHA/ACC guideline for the management of adults with congenital heart disease 1.

From the FDA Drug Label

Sildenafil tablets are indicated for the treatment of pulmonary arterial hypertension (WHO Group I) in adults to improve exercise ability and delay clinical worsening. The efficacy of sildenafil tablets in the treatment of pulmonary arterial hypertension (PAH) has not been adequately evaluated in patients taking bosentan. Sildenafil tablets are a prescription medicine used in adults to treat pulmonary arterial hypertension (PAH). With PAH, the blood pressure in your lungs is too high. Your heart has to work hard to pump blood into your lungs. Sildenafil tablets improve the ability to exercise and can slow down worsening changes in your physical condition

The utility of Sildenafil in Adult Congenital Heart Disease is to treat pulmonary arterial hypertension (PAH), which can improve exercise ability and delay clinical worsening.

• Key benefits of Sildenafil in PAH include:
  • Improved exercise ability
  • Delayed clinical worsening
• Important considerations:
  • Efficacy not established in patients taking bosentan
  • Not for use in children
  • Contains the same medicine as sildenafil citrate tablets, which are used to treat erectile dysfunction
  • Should not be taken with nitrate medicines 2, 2

From the Research

Utility of Sildenafil in Adult Congenital Heart Disease

• Sildenafil, a phosphodiesterase type 5 inhibitor, has been shown to be effective in treating pulmonary arterial hypertension (PAH) in adults with congenital heart disease (CHD) 3.
• A study published in 2010 demonstrated that oral sildenafil significantly increased six-minute walk test distances and improved World Health Organization (WHO) functional class and cardiopulmonary hemodynamics in patients with PAH related to CHD 3.
• Another study published in 2005 found that sildenafil improved exercise capacity and oxyhaemoglobin saturations in children with pulmonary hypertension, including those with congenital heart disease 4.
• The combination of sildenafil and bosentan has also been shown to be safe and effective in patients with CHD-related PAH and Eisenmenger physiology 5, 6.
• A prospective open-label study published in 2021 found that the addition of generic bosentan to sildenafil improved hemodynamic parameters and low-risk criteria scores in patients with PAH-CHD 7.

Mechanism of Action

• Sildenafil works by inhibiting phosphodiesterase type 5, leading to increased levels of cyclic guanosine monophosphate (cGMP) and subsequent pulmonary vasodilation 3.
• The combination of sildenafil and bosentan may have additive effects on pulmonary vasodilation and vascular remodeling 6.

Clinical Implications

• Sildenafil may be a useful treatment option for patients with PAH related to CHD, particularly those who are not responding to other therapies 3.
• The combination of sildenafil and bosentan may be considered for patients with CHD-related PAH and Eisenmenger physiology who are not responding to monotherapy 6.
• Further studies are needed to fully understand the efficacy and safety of sildenafil and bosentan in patients with PAH-CHD 7.