What are the considerations for using Tadalafil (tadalafil) in patients at risk for stroke?

From the Guidelines

Tadalafil should be used with caution in patients at risk for stroke, and a thorough cardiovascular risk assessment should be conducted before prescribing, as indicated by the 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease 1. When considering the use of tadalafil in patients at risk for stroke, several factors must be taken into account to minimize potential risks.

• Patients with a recent history of stroke, uncontrolled hypertension, or unstable cardiovascular disease may need to avoid tadalafil entirely due to the potential for increased stroke risk.
• For those with moderate risk factors, starting at a lower dose (such as 5mg) rather than the standard 10mg dose is advisable, with careful monitoring for adverse effects, as tadalafil can cause vasodilation and modest drops in blood pressure (typically 5-8 mmHg systolic) 1.
• The medication should not be combined with nitrates under any circumstances, as this can cause dangerous hypotension, and patients on long-acting nitrate therapy who want to use a phosphodiesterase type 5 inhibitor should be guided by the need for continued nitrate therapy versus other alternative options available to the treating clinician 1.
• Alpha-blockers should be used cautiously with tadalafil, with doses separated by at least 4 hours.
• Patients should report any symptoms such as severe headache, dizziness, visual changes, or neurological symptoms while taking tadalafil, as these could indicate cerebrovascular issues requiring immediate medical attention.
• Regular blood pressure monitoring is recommended for at-risk patients using tadalafil, and the decision to use tadalafil should be guided by the latest clinical practice guidelines, such as the 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease 1.

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. Cardiovascular and Cerebrovascular — Serious cardiovascular events, including myocardial infarction, sudden cardiac death, stroke, chest pain, palpitations, and tachycardia, have been reported postmarketing in temporal association with the use of tadalafil.

Tadalafil and Stroke Risk: Tadalafil is not recommended for patients who have had a stroke within the last 6 months. Additionally, serious cardiovascular events, including stroke, have been reported postmarketing in temporal association with the use of tadalafil. However, it is not possible to determine whether these events are related directly to tadalafil, to sexual activity, to the patient’s underlying cardiovascular disease, or to other factors 2, 2.

• Key Considerations:
  • Patients with a history of stroke should be carefully evaluated before prescribing tadalafil.
  • The risk of stroke may be increased in patients with underlying cardiovascular disease.
  • Patients should be advised to seek immediate medical attention if they experience any symptoms of a stroke.
• Clinical Decision: Tadalafil should be used with caution in patients at risk for stroke, and the potential benefits and risks of treatment should be carefully weighed. 2

From the Research

Tadalafil and Stroke Risk

• The relationship between tadalafil use and stroke risk is complex and has been investigated in several studies 3, 4, 5, 6, 7.
• A study published in 2024 found that tadalafil exposure was associated with lower adjusted rates of major adverse cardiovascular events, including stroke, in men with erectile dysfunction 4.
• Another study published in 2024 found that tadalafil and sildenafil were associated with significantly reduced risks of stroke in erectile dysfunction patients, with tadalafil showing more significant benefits 7.
• A study published in 2003 found that the incidence rate of presumed thrombotic strokes in tadalafil studies was comparable to the expected rate in the patient population 6.
• The use of tadalafil is contraindicated in patients receiving nitrate therapy due to the potential for significant hypotensive effects, which may increase the risk of stroke 5, 6.

Considerations for Using Tadalafil in Patients at Risk for Stroke

• Patients with a history of stroke or transient ischemic attack should be carefully evaluated before initiating tadalafil therapy 5.
• Tadalafil should be used with caution in patients with cardiovascular disease, including those with a history of myocardial infarction, unstable angina, or heart failure 3, 4, 5, 6.
• Patients taking tadalafil should be monitored for signs and symptoms of stroke, including sudden weakness or numbness in the face, arm, or leg, difficulty speaking or understanding speech, and sudden blurred vision or loss of vision 5, 6.
• The benefits and risks of tadalafil therapy should be carefully weighed in patients at risk for stroke, and alternative treatments should be considered if necessary 3, 4, 5, 6, 7.