Sildenafil Effects on Blood Pressure
Sildenafil causes modest decreases in systemic blood pressure (mean maximum decrease of 8/5 mmHg systolic/diastolic in healthy volunteers), with more pronounced effects when combined with antihypertensive medications, but does not cause clinically significant hypotension in patients with stable cardiovascular disease unless combined with nitrates. 1
Mechanism and Hemodynamic Effects
Sildenafil inhibits phosphodiesterase type-5 (PDE-5), leading to increased cyclic GMP in vascular smooth muscle, resulting in vasodilation primarily in the pulmonary vasculature but also causing mild peripheral arterial-venous dilatation. 1
Systemic Blood Pressure Effects
Single oral doses of 100 mg sildenafil produce maximum blood pressure decreases approximately 1-2 hours after dosing, with effects not different from placebo by 8 hours. 1
The magnitude of blood pressure reduction is not dose-related within the 25-100 mg range, as similar effects occur across this dosage spectrum. 1
Chronic dosing of 80 mg three times daily in healthy volunteers produces mean decreases of 9.0 mmHg systolic and 8.4 mmHg diastolic blood pressure. 1
In patients with systemic hypertension receiving chronic 80 mg three times daily, mean decreases are 9.4 mmHg systolic and 9.1 mmHg diastolic. 1
Patients with pulmonary arterial hypertension (PAH) experience lesser reductions—only 2 mmHg decreases in both systolic and diastolic pressures with chronic 80 mg three times daily dosing. 1
Interaction with Antihypertensive Medications
Sildenafil produces additive (not potentiating) blood pressure-lowering effects when combined with standard antihypertensive agents including beta-blockers, alpha-blockers, diuretics, ACE inhibitors, and calcium antagonists. 2
This additive effect is unlikely to cause clinically significant hypotension or increased incidence of adverse events in most patients. 2
Sildenafil does not increase the incidence of adverse events or hypotensive episodes when combined with one or more antihypertensive medications. 3
Care is needed when co-administering sildenafil with antihypertensive drugs to avoid excessive systemic hypotension, particularly in patients requiring multiple antihypertensive agents. 4
Critical Contraindication: Nitrate Interaction
The combination of sildenafil with organic nitrates is absolutely contraindicated due to synergistic and potentially life-threatening hypotension. 5, 1
Specific Timing Requirements
Nitrates are contraindicated within 24 hours after sildenafil use. 5
Sildenafil is contraindicated within 24 hours after nitrate use. 5
Tadalafil requires a 48-hour washout period before nitrate administration. 5
The suitable delay for vardenafil has not been definitively determined, though blood pressure generally returns to baseline by 24 hours. 5
Mechanism of Dangerous Interaction
Both sildenafil and nitrates increase cyclic GMP levels—sildenafil by inhibiting its degradation and nitrates by increasing its production—resulting in markedly exaggerated and prolonged vasodilation. 5
- This combination has been associated with profound hypotension, myocardial infarction, and death. 5
Safety in Cardiovascular Disease Populations
Placebo-controlled and open-label trials including men with ischemic heart disease showed no increase in myocardial infarction or serious cardiovascular events in sildenafil-treated patients versus placebo. 6
Stable Coronary Disease
Sildenafil demonstrates minimal adverse effects in men with stable ischemia, hypertension, and/or severe coronary artery disease. 3
In patients with ischemic heart disease, sildenafil reduces mean arterial and pulmonary pressure with little effect on heart rate, cardiac output, or systemic/pulmonary vascular resistance. 7
No association between sildenafil and increased cardiovascular morbidity or mortality has emerged in clinical trial analyses. 3
Unstable Cardiac Conditions
Sildenafil should be used with caution in patients with recent (less than 6 months) myocardial infarction, unstable angina, stroke, or recent life-threatening arrhythmias, as data in these populations are not available. 6
- Nitroglycerin should be avoided in patients with initial systolic blood pressure less than 90 mmHg or 30 mmHg or more below baseline. 5
Pulmonary Arterial Hypertension Effects
In PAH patients, sildenafil reduces mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) while increasing cardiac index, with apparent systemic hemodynamic effects unlike inhaled nitric oxide. 5
Sildenafil has been shown to decrease elevated pulmonary vascular resistance and pulmonary artery pressures in patients with pulmonary vascular disease. 3
The American College of Chest Physicians recognizes sildenafil as effective for PAH, improving exercise capacity, functional class, and hemodynamic parameters. 4
Common Pitfalls and Clinical Considerations
The most common adverse events—headache (34-57% of patients), flushing, epistaxis, and visual disturbances—result from sildenafil's vasodilating properties rather than dangerous hypotension. 4, 2
Sildenafil has no effect on cardiac contractility, as PDE-5 is not found in cardiomyocytes and sildenafil does not affect cyclic adenosine monophosphate levels in the vasculature. 3, 7
The absence of effect on cardiac output supports the lack of inotropic effect. 7
Beneficial hemodynamic changes have been observed with sildenafil in patients with congestive heart failure with underlying ischemic and other dilated cardiomyopathies. 3