How does sildenafil (Viagra) influence systemic blood pressure and what precautions are required in patients with hypertension, heart failure, recent myocardial infarction, or who are taking nitrates or other antihypertensive agents?

Effects of Sildenafil (Viagra) on Blood Pressure

Sildenafil causes mild, transient decreases in systemic blood pressure (mean maximum reduction of 8/5 mmHg), but this effect is generally well-tolerated in most patients and does not cause clinically significant hypotension when used alone at therapeutic doses. 1

Mechanism and Hemodynamic Effects

Sildenafil inhibits phosphodiesterase type 5 (PDE5), which increases cyclic GMP in vascular smooth muscle, causing vasodilation primarily in the pulmonary vasculature but also affecting systemic circulation to a lesser degree. 1

Specific blood pressure effects include:

• Single oral doses of 25-100 mg produce decreases in supine blood pressure of approximately 8/5 mmHg, with maximum effect occurring 1-2 hours after dosing. 1
• The blood pressure reduction is not dose-related within the therapeutic range (25-100 mg), meaning higher doses do not cause proportionally greater drops. 1
• Chronic dosing of 80 mg three times daily in healthy volunteers produces mean decreases of 9.0/8.4 mmHg in supine blood pressure. 1
• Heart rate remains unchanged with sildenafil administration. 1, 2

Critical Drug Interactions and Contraindications

Absolute Contraindication: Nitrates

The combination of sildenafil with organic nitrates is absolutely contraindicated due to synergistic, potentially life-threatening hypotension. 3, 4

Specific timing requirements:

• Nitrates are contraindicated within 24 hours after sildenafil use. 3, 4
• Sildenafil is contraindicated within 24 hours after nitrate use. 3, 4
• Tadalafil requires a 48-hour washout period before nitrate administration. 3, 4
• The suitable delay for vardenafil has not been definitively determined, though blood pressure generally returns to baseline by 24 hours. 3

The mechanism involves both drugs increasing cGMP levels at different points along the nitric oxide-cGMP pathway, causing synergistic vasodilation. 2 This interaction has been associated with profound hypotension, myocardial infarction, and death. 3

Use with Antihypertensive Medications

Sildenafil can be used with standard antihypertensive agents, but blood pressure monitoring is required due to additive blood pressure-lowering effects. 4, 1

Key considerations:

• Retrospective analysis of concomitant use with beta blockers, alpha blockers, diuretics, ACE inhibitors, and calcium antagonists did not show increased adverse events or significant hypotension episodes compared to sildenafil alone. 2
• The incidence of hypotension, orthostatic hypotension, and syncope was <2% and identical between sildenafil and placebo groups. 2
• Monitor blood pressure when co-administering blood pressure-lowering drugs with sildenafil. 1
• Care is needed to avoid excessive systemic hypotension when PAH-targeted medications like sildenafil are combined with antihypertensive drugs. 4

Special Populations Requiring Caution

Carefully consider sildenafil use in patients with:

• Resting hypotension (BP <90/50 mmHg). 1
• Fluid depletion. 1
• Severe left ventricular outflow obstruction. 1
• Autonomic dysfunction. 1
• Patients on antihypertensive therapy where additional blood pressure reduction could be problematic. 1

Cardiovascular Safety Profile

In placebo-controlled trials, sildenafil did not increase the incidence of myocardial infarction, serious cardiovascular events, or death compared to placebo, even in patients with stable ischemic heart disease. 5, 6

However, data are lacking for:

• Recent myocardial infarction (<6 months). 5
• Unstable angina. 5
• Recent stroke. 5
• Recent life-threatening arrhythmias. 5

Use sildenafil with caution in these unstable cardiac conditions. 5

Common Side Effects Related to Vasodilation

The most commonly reported cardiovascular adverse events are manifestations of vasodilation:

• Headache: 16-57% of patients. 4, 2
• Flushing: 10% of patients. 4, 2
• Dizziness: 2% of patients. 2
• Epistaxis: 13% in PAH patients with connective tissue disease (higher with concomitant vitamin K antagonists). 1

Clinical Approach for Cardiac Patients

Before prescribing sildenafil to patients with known cardiac disease or multiple cardiovascular risk factors:

1. Discuss the cardiac risk of sexual activity itself (estimated at 3-5 metabolic equivalents of exercise). 7
2. Perform complete medical assessment, including exercise stress test if appropriate, to determine if patients can achieve the physiologic workload associated with sexual intercourse. 5, 6
3. Verify no nitrate use within the past 24 hours and counsel patients never to combine these medications. 3
4. Review all antihypertensive medications and plan for blood pressure monitoring. 1
5. Patients with stable angina controlled on medications can safely use sildenafil. 7

Pulmonary vs. Systemic Effects

While sildenafil is approved for pulmonary arterial hypertension and produces significant reductions in pulmonary artery pressure and pulmonary vascular resistance, its systemic blood pressure effects are more modest. 3, 4 In PAH patients receiving chronic 80 mg three times daily dosing, systemic blood pressure decreases were only 2 mmHg for both systolic and diastolic pressures—substantially less than in healthy volunteers or hypertensive patients. 1