What precautions should be taken when prescribing sildenafil (phosphodiesterase type 5 inhibitor) to adult males with a history of cardiovascular disease, hypertension, or diabetes?

Sildenafil Precautions in Men with Cardiovascular Disease, Hypertension, or Diabetes

Before prescribing sildenafil to any man with cardiovascular comorbidities, you must first stratify his cardiac risk using the Princeton Consensus approach—low-risk patients can safely receive sildenafil without additional cardiac evaluation, indeterminate-risk patients require cardiovascular assessment before treatment, and high-risk patients must defer sexual activity and sildenafil until their cardiac condition is stabilized. 1, 2

Absolute Contraindications That Override All Other Considerations

• Sildenafil is absolutely contraindicated with any form of nitrate medication (nitroglycerin tablets, patches, sprays, ointments, isosorbide mononitrate/dinitrate, or "poppers") due to life-threatening hypotension risk 1, 2, 3
• Do not administer nitrates within 24 hours of sildenafil use 4
• Sildenafil is contraindicated in patients with known hypersensitivity to the drug 3

Cardiovascular Risk Stratification (Princeton Consensus)

Low-Risk Patients (Can Safely Receive Sildenafil)

• Asymptomatic coronary artery disease with fewer than 3 cardiac risk factors 5
• Controlled hypertension 5
• Mild stable angina 5
• Successful coronary revascularization 5
• Uncomplicated past myocardial infarction 5
• Mild valvular disease 5
• Heart failure NYHA Class I 5

Indeterminate-Risk Patients (Require Cardiovascular Assessment First)

• Patients with 3 or more cardiac risk factors 1
• Moderate stable angina 1
• Recent myocardial infarction (within 2-6 weeks) 1
• Heart failure NYHA Class II 1
• Consider exercise stress testing to determine if the patient can perform moderate physical activity (≥5 metabolic equivalents) before prescribing sildenafil 1, 6

High-Risk Patients (Defer Sexual Activity and Sildenafil)

• Unstable or refractory angina 1
• Uncontrolled hypertension 3, 7
• Heart failure NYHA Class III-IV 1
• Recent myocardial infarction or stroke (within 2 weeks) 1
• High-risk arrhythmias 1
• Hypertrophic obstructive cardiomyopathy 1
• Severe left ventricular outflow obstruction 3
• These patients must be referred to cardiology and stabilized before any consideration of sildenafil 1, 2

Specific Precautions by Comorbidity

Hypertension

• Sildenafil causes mild, transient decreases in blood pressure (mean additional reduction of 8 mmHg systolic and 7 mmHg diastolic when combined with antihypertensives) 7
• Monitor blood pressure when co-administering with antihypertensive drugs 3
• Use with caution in patients with resting hypotension (BP <90/50 mmHg) 3
• Exercise particular caution with alpha-blockers: patients should be stable on alpha-blocker therapy before initiating sildenafil, and sildenafil should be started at the lowest dose (25 mg) 3, 7
• Similar caution applies to mixed alpha/beta blockers (carvedilol, labetalol) 7
• Sildenafil is generally well-tolerated with other antihypertensive classes, though treatment response remains high (71% vs 27% placebo) 8

Diabetes

• Men with diabetes have more severe erectile dysfunction at baseline and may respond less robustly to sildenafil, but the drug remains effective (63% treatment response vs 24% placebo) 5, 8
• Consider screening for testosterone deficiency, as men with hypogonadism respond less robustly to sildenafil alone 5
• Combining sildenafil with testosterone therapy may be more effective than sildenafil alone in men with confirmed hypogonadism 5
• Be aware that diabetes is a risk factor for non-arteritic anterior ischemic optic neuropathy (NAION) 3

Cardiovascular Disease (General)

• Postmarketing surveillance data from over 13,000 patients and 7 years of international data show no increased risk of myocardial infarction or death when sildenafil is used according to labeling 7, 4
• Sildenafil does not reduce exercise tolerance or increase coronary oxygen consumption in men with known coronary artery disease 2, 7
• Treatment response remains high in men with cardiovascular disease/hypertension (71% vs 27% placebo) 8
• The adverse event profile is similar between those with and without coronary artery disease 7

Dosing Strategy for Patients with Comorbidities

• Standard starting dose: 50 mg taken approximately 1 hour before sexual activity, not more than once daily 2, 5
• Reduced starting dose (25 mg) is recommended for:
  • Elderly patients (≥65 years) 2
  • Hepatic impairment 2, 5
  • Renal impairment 2, 5
  • Patients taking CYP3A4 inhibitors (ritonavir, ketoconazole, erythromycin, cimetidine) 2, 5, 3
• Dose titration: Allow at least 5 separate attempts at the starting dose before declaring treatment failure or adjusting dose 2, 5
• Maximum dose: 100 mg, but higher doses are associated with greater risk of adverse effects 5

Additional Safety Precautions

Pulmonary Veno-Occlusive Disease (PVOD)

• Sildenafil may significantly worsen cardiovascular status in patients with PVOD 3
• If signs of pulmonary edema occur, consider the possibility of PVOD and discontinue sildenafil 3

Bleeding Disorders

• The safety of sildenafil is unknown in patients with bleeding disorders or active peptic ulceration 3
• Epistaxis incidence is higher in patients taking concomitant vitamin K antagonists (9% vs 2%) 3

Visual Loss (NAION)

• Advise patients to seek immediate medical attention for sudden loss of vision in one or both eyes 3
• Risk factors for NAION include: age >50, diabetes, hypertension, coronary artery disease, hyperlipidemia, smoking, and "crowded disc" anatomy 3
• Use caution in patients with retinitis pigmentosa 3
• Discuss increased NAION risk with patients who have already experienced NAION in one eye 3

Hearing Loss

• Advise patients to report sudden decrease or loss of hearing immediately 3

Autonomic Dysfunction and Volume Depletion

• Use caution in patients with autonomic dysfunction or fluid depletion, as vasodilatory effects may be poorly tolerated 3

Drug Interactions Requiring Dose Adjustment

• CYP3A4 inhibitors (ritonavir, ketoconazole, itraconazole, erythromycin, cimetidine): Reduce sildenafil starting dose to 25 mg 2, 5, 3
• Do not combine sildenafil with other PDE5 inhibitors (tadalafil, vardenafil)—this increases adverse effects without improving efficacy 9

Mandatory Follow-Up and Monitoring

• Periodic follow-up between 4 weeks and 6 months should assess: 5
  • Efficacy and side effects
  • Verification that cardiovascular health hasn't changed
  • Review of new medications
  • Changes in overall health status
  • Dose adjustment or treatment modification as needed

Common Adverse Effects to Counsel Patients About

• Headache, flushing, dyspepsia, nasal congestion (transient and mild-to-moderate at therapeutic doses) 2
• Serious adverse events occur in <2% of patients, with no significant difference from placebo 5
• Erections lasting >4 hours require immediate medical attention 3

Critical Patient Education Points

• Sexual stimulation is necessary for sildenafil to work 2
• Take approximately 1 hour before sexual activity, not more than once daily 2
• Take on an empty stomach for optimal absorption 2
• Never use with nitrates or "poppers" 3
• Report any chest pain, sudden vision or hearing loss, or prolonged erections immediately 3