What are the risks and precautions associated with using Tadalafil (tadalafil) in patients with a history of cardiovascular disease, particularly stroke?

From the Guidelines

Tadalafil should be used with caution in patients with a history of cardiovascular disease, particularly stroke, due to the potential risk of severe hypotension and stroke. When considering the use of tadalafil in patients with a history of stroke, it is essential to weigh the benefits against the potential risks, including the possibility of stroke, as phosphodiesterase type 5 inhibitors like tadalafil can cause vasodilation, potentially compromising cerebral blood flow regulation in patients with existing cerebrovascular disease 1. Key precautions include:

• Avoiding concomitant use with nitrate medications, which are often used to treat chronic coronary disease, due to the risk of severe hypotension 1
• Avoiding use within 48 hours of nitroglycerine, with a longer interval of 48 hours recommended for tadalafil due to its longer half-life of 17.5 hours 1
• Starting with a lower dose, such as 5mg, and carefully monitoring for adverse effects in patients with a history of stroke
• Conducting a thorough cardiovascular evaluation before considering treatment in patients with a history of stroke
• Immediately seeking medical attention if experiencing chest pain, dizziness, or stroke-like symptoms during treatment. The potential benefits of tadalafil, including improved sexual function as measured by the International Index of Erectile Function 1, must be carefully balanced against these risks in patients with a history of cardiovascular disease, particularly stroke.

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: ... stroke within 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 may be associated with an increased risk of stroke in certain patients, particularly those with a history of cardiovascular disease. Key considerations include:

• Patients with a history of stroke within the last 6 months should not use tadalafil.
• Tadalafil has mild systemic vasodilatory properties that may result in transient decreases in blood pressure, which could potentially increase the risk of stroke in susceptible individuals.
• Patients with underlying cardiovascular disease should be carefully evaluated before prescribing tadalafil, as they may be more sensitive to the effects of vasodilators 2.

From the Research

Risks and Precautions of Tadalafil in Patients with Cardiovascular Disease

The use of tadalafil in patients with a history of cardiovascular disease, particularly stroke, has been investigated in several studies.

• Tadalafil is a phosphodiesterase inhibitor that has been shown to have cardiovascular benefits in patients with erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension (PAH) 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 heart failure, acute myocardial infarction, and mortality compared with sildenafil or no treatment 3.
• Another study found that tadalafil exposure was associated with lower adjusted rates of major adverse cardiovascular events (MACE) and all-cause death in men with ED 4.
• Tadalafil has also been shown to have a cardiovascular-protective effect, elevating endothelial cell-derived nitric oxide levels, activating protein kinase A, and improving hemodynamic indexes 5.

Association with Stroke

• A study found that tadalafil was associated with a lower risk of stroke (RR 0.66) in erectile dysfunction patients, with tadalafil showing more significant benefits compared to sildenafil 6.
• Another study found that tadalafil exposure was associated with lower adjusted rates of MACE, including stroke, in men with ED 4.
• The evidence suggests that tadalafil may have a beneficial effect on cardiovascular health, including a reduced risk of stroke, in patients with ED and cardiovascular disease 5, 4, 6.

Precautions and Considerations

• While tadalafil has been shown to have cardiovascular benefits, its use in patients with a history of cardiovascular disease, particularly stroke, should be carefully considered and monitored by a healthcare professional.
• Patients with ED and cardiovascular disease should be evaluated for their individual risk factors and medical history before starting tadalafil treatment 3, 7.
• Further studies are needed to fully understand the effects of tadalafil on cardiovascular health and to determine its potential role in the prevention or treatment of heart failure and stroke 3, 6.