What are the cardiac effects of Tadalafil (Cialis)?

Cardiac Effects of Tadalafil

Tadalafil demonstrates a favorable cardiovascular safety profile with minimal hemodynamic effects and no increased risk of serious cardiovascular events compared to placebo, though it is absolutely contraindicated with nitrate medications due to life-threatening hypotension risk. 1

Hemodynamic and Blood Pressure Effects

Baseline Cardiovascular Impact

• Tadalafil causes minimal blood pressure reduction in healthy subjects, with mean reductions of approximately 3-4 mmHg systolic and 1-2 mmHg diastolic 1
• A single 100-mg dose (5 times the maximum recommended dose) produced a mean QTc prolongation of only 3.5 milliseconds and increased heart rate by 3.1 beats per minute, neither clinically significant 1
• In patients with stable coronary artery disease and exercise-induced ischemia, tadalafil 10 mg showed no clinically meaningful difference in time to cardiac ischemia compared to placebo (mean difference of 3 seconds) 1

Interactions with Antihypertensive Medications

• With amlodipine (5 mg daily): Tadalafil 10 mg caused additional blood pressure reduction of 3/2 mmHg; at 20 mg dose, no clinically significant differences occurred 1
• With angiotensin II receptor blockers: Tadalafil 20 mg produced blood pressure differences of 8/4 mmHg compared to placebo 1
• With bendrofluazide (2.5 mg daily): Additional reduction of 6/4 mmHg with tadalafil 10 mg 1
• With enalapril (10-20 mg daily): Additional reduction of 4/1 mmHg with tadalafil 10 mg 1
• With metoprolol (25-200 mg daily): Additional reduction of 5/3 mmHg with tadalafil 10 mg 1

Alcohol Interaction

• High-dose alcohol (0.7 g/kg, equivalent to 6 ounces of 80-proof vodka) combined with tadalafil 10-20 mg caused clinically significant blood pressure decreases, postural dizziness, and orthostatic hypotension in some subjects 1
• Lower alcohol doses (0.6 g/kg, approximately 4 ounces) with tadalafil 20 mg did not cause orthostatic hypotension 1

Absolute Contraindication: Nitrate Medications

The concurrent use of tadalafil with any nitrate medication is absolutely contraindicated due to potentially fatal hypotension. 2, 3

Mechanism and Timing

• Both tadalafil and nitrates work through the nitric oxide-cGMP pathway, creating profound and prolonged vasodilation that can result in myocardial infarction, stroke, or death 3
• Tadalafil has a half-life of 17.5 hours, requiring at least 48 hours after the last tadalafil dose before any nitrate can be safely administered 2, 3, 1
• In the exercise stress testing study, subjects who received sublingual nitroglycerin post-exercise after tadalafil experienced clinically significant blood pressure reductions 1

Clinical Management

• Patients on long-acting nitrate therapy (such as isosorbide mononitrate) should not use tadalafil 3
• Consider transitioning from nitrate therapy to alternative antianginal agents (beta-blockers, calcium channel blockers, or ranolazine) if tadalafil use is desired and clinically appropriate 3

Cardiovascular Safety Data

Serious Cardiovascular Events

• Across 36 clinical trials with 12,487 men receiving tadalafil (5,771 patient-years exposure), the incidence of serious cardiovascular events was 0.40 per 100 patient-years, comparable to placebo at 0.43 per 100 patient-years 4
• Myocardial infarction rate in tadalafil-treated patients was 0.33 per 100 patient-years across all studies, comparable to placebo (0.41 per 100 patient-years) and age-standardized male population (0.6 per 100 patient-years) 5
• Cardiac mortality rate was 0.12 per 100 patient-years in tadalafil-treated patients, lower than the 0.26 per 100 patient-years in age-standardized male populations 5
• The American College of Cardiology confirms that PDE5 inhibitors like tadalafil have shown no specific concerns regarding cardiovascular events in patients with cardiovascular disease 2

Patient Population Characteristics

• Trial populations included patients with significant cardiovascular comorbidities: hypertension (31%), diabetes (21%), hyperlipidemia (17%), and coronary artery disease (5%) 4
• Serious cardiovascular events were rare and similar in frequency between tadalafil and placebo groups across all dosing regimens (as needed, 3 times weekly, or once daily) 4

Therapeutic Cardiovascular Applications

Pulmonary Arterial Hypertension

• For treatment-naive PAH patients with WHO functional class II-III, combination therapy with ambrisentan and tadalafil (40 mg daily) improves 6-minute walk distance by a median of 49 meters versus 24 meters with monotherapy 6
• For stable PAH patients on background ambrisentan therapy, adding tadalafil 40 mg daily significantly improves 6-minute walk distance (mean change 54.4 meters vs 18.3 meters with placebo) 6
• The European Society of Cardiology notes that tadalafil, as a selective PDE5 inhibitor, causes significant pulmonary vasodilation with maximum effects at 75-90 minutes and exerts antiproliferative effects 6

Potential Cardioprotective Mechanisms

• Tadalafil elevates endothelial cell-derived nitric oxide levels, activates protein kinase A, upregulates intracellular Ca2+ concentration, and improves hemodynamic indexes 7
• Recent research suggests potential benefits in ischemic cardiomyopathy and heart failure, though clinical trial evidence remains limited 8
• A retrospective cohort study found tadalafil use in patients with erectile dysfunction and coronary artery disease was associated with decreased incidence of heart failure, acute myocardial infarction, and mortality compared to sildenafil or no treatment 8

Common Pitfalls and Caveats

• Never prescribe tadalafil to patients taking nitrates - verify all medications including as-needed nitroglycerin 2, 3
• In emergency situations where a patient on tadalafil requires nitrate therapy, recognize that nitrates cannot be safely given for at least 48 hours after the last tadalafil dose 2, 3
• Exercise caution when combining tadalafil with alpha-blockers like doxazosin; only consider in hemodynamically stable patients using the lowest tadalafil dose with close blood pressure monitoring 9
• Postmarketing surveillance has reported serious cardiovascular events (myocardial infarction, sudden cardiac death, stroke) in temporal association with tadalafil use, though most patients had preexisting cardiovascular risk factors and causality cannot be definitively established 1
• Cardiovascular disease and erectile dysfunction share common risk factors; complete cardiovascular assessment may be necessary before prescribing tadalafil 9, 5