What is the relationship between Phosphodiesterase type 5 (PDE5) inhibitors and cardiac function?

From the Guidelines

PDE5 inhibitors are generally safe for most patients with stable cardiovascular disease and can have beneficial cardiac effects, improving exercise capacity and quality of life in patients with heart failure and pulmonary hypertension. The relationship between Phosphodiesterase type 5 (PDE5) inhibitors and cardiac function is complex, but recent evidence suggests that these medications can be beneficial for patients with certain cardiac conditions 1.

Key Points

• PDE5 inhibitors, such as sildenafil, tadalafil, and vardenafil, can improve exercise capacity and quality of life in patients with heart failure and pulmonary hypertension.
• These medications work by dilating blood vessels, which can lower blood pressure slightly and reduce cardiac workload.
• Typical doses range from 25-100 mg for sildenafil, 5-20 mg for tadalafil, and 5-20 mg for vardenafil, taken as needed before sexual activity.
• However, these drugs are contraindicated in patients taking nitrates due to the risk of severe hypotension.
• Patients with unstable angina, recent heart attack or stroke, or uncontrolled hypertension should use caution and consult their cardiologist before using PDE5 inhibitors.

Important Considerations

• The improvement in erectile function was related to higher dose for sildenafil and vardenafil, but not tadalafil 1.
• PDE5 inhibitors can be used in combination with other ED therapies, resulting in greater improvements in erectile function and frequency of penile penetration or maintenance of erection 1.
• It's essential to note that while these medications can have cardiac benefits, they should not be used solely for cardiovascular treatment without proper medical supervision.

Cardiac Effects

• PDE5 inhibitors can have beneficial cardiac effects, including improved exercise capacity and quality of life in patients with heart failure and pulmonary hypertension 1.
• These medications can lower blood pressure slightly and reduce cardiac workload, which can be beneficial for patients with certain cardiac conditions.

From the FDA Drug Label

The approximately 4,000-fold selectivity for PDE-5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility Single oral doses of sildenafil up to 100 mg in healthy volunteers produced no clinically relevant effects on ECG. After chronic dosing of 80 mg TID to patients with PAH, no clinically relevant effects on ECG were reported

The PDE5 inhibitors, such as sildenafil, have a high selectivity for PDE5 over PDE3, which is involved in cardiac contractility.

• The drug labels report no clinically relevant effects on ECG in healthy volunteers and patients with PAH after single or chronic dosing of sildenafil.
• Key points about the relationship between PDE5 inhibitors and cardiac function include:
  • High selectivity for PDE5 over PDE3
  • No clinically relevant effects on ECG
  • Decreases in blood pressure, but no significant effects on cardiac contractility 2 2

From the Research

Relationship between PDE5 Inhibitors and Cardiac Function

• PDE5 inhibitors, such as sildenafil, tadalafil, and vardenafil, have been found to have cardioprotective effects, including vasodilation, decreased apoptosis, and reduced cell proliferation 3, 4, 5.
• These inhibitors have been shown to be beneficial in the treatment of various cardiovascular diseases, including ischemia/reperfusion injury, myocardial infarction, cardiac hypertrophy, cardiomyopathy, and congestive heart failure 3, 4, 5, 6.
• The pharmacokinetics and pharmacodynamics of PDE5 inhibitors are important considerations in their risk-benefit profile and clinical use 3, 4.
• Some studies have suggested that PDE5 inhibitors may reduce infarct size and improve cardiac function in patients with cardiovascular disease 3, 4, 5.
• However, caution is urged when using PDE5 inhibitors in patients with systolic heart failure and pulmonary hypertension due to the potential risk of sudden death 7.

Mechanisms of PDE5 Inhibitors

• PDE5 inhibitors work by inhibiting the degradation of cyclic guanosine monophosphate (cGMP), a potent vasodilator and nitric oxide (NO) donor 4, 5, 6.
• This leads to increased levels of cGMP, resulting in vasodilation and improved cardiac function 4, 5, 6.
• PDE5 inhibitors have also been shown to have anti-apoptotic and anti-proliferative effects, which may contribute to their cardioprotective effects 3, 4, 5.

Clinical Uses of PDE5 Inhibitors

• PDE5 inhibitors are currently approved for the treatment of erectile dysfunction and pulmonary arterial hypertension 4, 5, 6.
• Emerging evidence suggests that PDE5 inhibitors may also be beneficial in the treatment of other cardiovascular diseases, including hypertension, myocardial infarction, stroke, and peripheral arterial disease 4, 5, 6.