What is the effect of Tadalafil (Cialis) on heart failure?

From the Guidelines

Tadalafil is not recommended for routine use in patients with heart failure with preserved ejection fraction (HFpEF) due to lack of evidence showing improvement in outcomes such as morbidity, mortality, and quality of life. According to the 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure 1, routine use of phosphodiesterase-5 inhibitors, such as tadalafil, to increase activity or quality of life in patients with HFpEF is ineffective. The RELAX trial, which randomized 216 patients with EF ≥50% on stable HF therapy and with reduced exercise tolerance to phosphodiesterase-5 inhibition with sildenafil or placebo, did not show improvement in oxygen consumption or exercise tolerance 1.

However, tadalafil may be beneficial for patients with heart failure and pulmonary hypertension, as it has been shown to improve exercise capacity and reduce pulmonary vascular resistance in patients with pulmonary arterial hypertension (PAH) 1. The typical dosage ranges from 5-40mg daily, with heart failure patients often starting at lower doses (5-10mg) and gradually increasing as tolerated. Tadalafil works by inhibiting phosphodiesterase type 5 (PDE5), which increases cyclic guanosine monophosphate (cGMP) levels, leading to vasodilation in pulmonary vessels and improved right ventricular function.

Key considerations when using tadalafil in heart failure patients include:

• Starting with lower doses and gradually increasing as tolerated
• Monitoring for common side effects such as headache, flushing, and nasal congestion
• Avoiding use in patients taking nitrates due to the risk of severe hypotension
• Undergoing comprehensive cardiac evaluation, including echocardiography and possibly right heart catheterization, to confirm pulmonary hypertension
• Regular follow-up to monitor response and adjust dosing as needed.

From the FDA Drug Label

Patients with left ventricular outflow obstruction, (e.g., aortic stenosis and idiopathic hypertrophic subaortic stenosis) can be sensitive to the action of vasodilators, including PDE5 inhibitors The following groups of patients with cardiovascular disease were not included in clinical safety and efficacy trials for tadalafil, and therefore until further information is available, tadalafil is not recommended for the following groups of patients: New York Heart Association Class 2 or greater heart failure in the last 6 months As with other PDE5 inhibitors, tadalafil has mild systemic vasodilatory properties that may result in transient decreases in blood pressure

The use of tadalafil is not recommended in patients with New York Heart Association Class 2 or greater heart failure in the last 6 months, as they were not included in clinical safety and efficacy trials for tadalafil 2.

• Tadalafil has mild systemic vasodilatory properties that may result in transient decreases in blood pressure.
• Patients with severely impaired autonomic control of blood pressure may be particularly sensitive to the actions of vasodilators, including PDE5 inhibitors. Therefore, tadalafil should be used with caution in patients with underlying cardiovascular disease.

From the Research

Effect of Tadalafil on Heart Failure

• Tadalafil, a phosphodiesterase inhibitor, has been investigated for its potential benefits in heart failure (HF) due to its cardiovascular benefits in erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension (PAH) 3.
• Studies in animal models have demonstrated improved left ventricular function and contractility, with reduced adverse remodeling and hypertrophy, suggesting a potential benefit of tadalafil use in ischemic cardiomyopathy and HF 3.
• A retrospective cohort study found that tadalafil use in patients with ED and coronary artery disease was associated with a significant decrease in the incidence of HF, acute myocardial infarction, and mortality compared with sildenafil or no treatment 3.
• However, a randomized controlled trial in patients with comorbid PAH and HF with preserved ejection fraction demonstrated no significant benefit with the use of tadalafil 3.
• The phosphodiesterase type 5 (PDE-5) inhibitors, including tadalafil, have been shown to improve endothelial dysfunction, increase exercise tolerance, decrease pulmonary vascular resistance and pulmonary artery pressure, and increase cardiac index in HF patients 4.
• Tadalafil's mechanism of action involves the inhibition of PDE5, leading to increased levels of nitric oxide and cyclic guanosine monophosphate, which facilitates smooth muscle relaxation and may have potential benefits in cardiovascular diseases, including HF 5.
• Further studies are needed to clarify the pharmacological effects of tadalafil on cardiovascular protection beyond PDE5 inhibition and to determine its role in the prevention or treatment of HF 3, 5.

Drug Interactions and Safety

• Tadalafil is safe when used with most antihypertensive agents, but co-administration with nitrates or α-blockers can cause severe hypotension and syncope 6.
• Dose adjustment is necessary when tadalafil is co-administered with cytochrome P (CYP) 3A inhibitors or inducers, which can influence its side-effect profile 6.
• The combination of oral tadalafil and bosentan (endothelin receptor antagonist) reduces tadalafil levels and requires dose adjustment 6.

Pathophysiology of Heart Failure

• Heart failure is an epidemic disease characterized by cellular, structural, and neurohumoral modulations that affect the phenotype being present 7.
• The understanding of the underlying pathophysiology of heart failure is essential to initiate the adequate therapeutic option individually for each patient 7.
• Modulation of the activated systems by ß-blocker, ACE-inhibitors, and ARNI can improve outcome and symptoms in heart failure patients with left ventricular dysfunction 7.