From the Guidelines
Sildenafil improves cardiac output in patients with pulmonary hypertension by reducing pulmonary vascular resistance and promoting vasodilation, as evidenced by the most recent and highest quality study 1.
Mechanism of Action
Sildenafil works by selectively inhibiting phosphodiesterase type 5 (PDE5) in the pulmonary vasculature, leading to an increase in cyclic guanosine monophosphate (cGMP) levels, which promotes smooth muscle relaxation specifically in areas with high PDE5 concentration. This mechanism allows the right ventricle to pump blood more efficiently through the lungs, decreasing right ventricular afterload and improving overall cardiac function.
Clinical Evidence
The study by 1 demonstrated that sildenafil reduces mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension (PAH), resulting in improved exercise capacity and functional class. The medication is typically prescribed at 20 mg three times daily, though doses may range from 20-80 mg three times daily depending on clinical response and tolerance.
Key Benefits
The key benefits of sildenafil in patients with pulmonary hypertension include:
- Improved exercise capacity
- Improved functional class
- Reduced pulmonary vascular resistance
- Decreased right ventricular afterload
- Prevention of right heart failure, which is the primary cause of death in pulmonary hypertension
Side Effects
Common side effects of sildenafil include headache, flushing, dyspepsia, and epistaxis, as reported in the study by 1. However, these side effects are generally mild and well-tolerated.
Clinical Recommendations
Based on the most recent and highest quality evidence, sildenafil is recommended as a first-line treatment for patients with pulmonary arterial hypertension, due to its ability to improve cardiac output and reduce morbidity and mortality 1.
From the FDA Drug Label
In patients with PAH, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation. The approximately 4,000-fold selectivity for PDE-5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility After chronic dosing of 80 mg TID sildenafil to patients with PAH, no clinically relevant effects on ECG were reported After chronic dosing of 80 mg TID sildenafil to patients with PAH, lesser reductions than above in systolic and diastolic blood pressures were observed (a decrease in both of 2 mmHg)
Sildenafil increases cardiac output in patients with pulmonary hypertension by vasodilating the pulmonary vascular bed, which reduces pulmonary vascular resistance. However, the effect of sildenafil on cardiac contractility is minimal due to its high selectivity for PDE-5 over PDE-3, an enzyme involved in controlling cardiac contractility 2. The overall effect on cardiac output is not explicitly quantified in the provided text.
From the Research
Effects of Sildenafil on Cardiac Output in Pulmonary Hypertension
- Sildenafil has been shown to increase cardiac output in patients with pulmonary hypertension, particularly in those with secondary pulmonary hypertension due to systolic heart failure 3, 4, 5.
- A study published in Circulation found that sildenafil reduced pulmonary vascular resistance and increased cardiac output with exercise in patients with systolic heart failure and secondary pulmonary hypertension 3.
- Another study published in The Annals of Pharmacotherapy found that sildenafil tended to increase cardiac output/cardiac index compared to baseline in patients with pulmonary hypertension 4.
- However, a more recent study published in the European Journal of Heart Failure found that sildenafil did not improve symptoms, quality of life, or exercise capacity in patients with heart failure with reduced ejection fraction and pulmonary hypertension 6.
Hemodynamic Effects of Sildenafil
- Sildenafil has been shown to reduce pulmonary arterial pressure and pulmonary vascular resistance in patients with pulmonary hypertension 3, 4, 7, 5.
- A study published in Vascular Pharmacology found that long-term use of sildenafil in patients with secondary pulmonary hypertension was associated with a sustained improvement in cardio-pulmonary hemodynamics, including a reduction in mean pulmonary arterial pressure and pulmonary vascular resistance 7.
- Sildenafil has also been shown to act as a selective pulmonary vasodilator during rest and exercise in patients with heart failure and pulmonary hypertension 5.
Clinical Implications
- The use of sildenafil in patients with pulmonary hypertension may be beneficial in improving exercise capacity and quality of life, particularly in those with secondary pulmonary hypertension due to systolic heart failure 3, 4, 5.
- However, the results of the SilHF study suggest that sildenafil may not be effective in improving symptoms, quality of life, or exercise capacity in all patients with heart failure with reduced ejection fraction and pulmonary hypertension 6.
- Further studies are needed to fully understand the effects of sildenafil on cardiac output and hemodynamics in patients with pulmonary hypertension, and to determine the optimal patient population and treatment regimen for this medication 4, 6.