What is the role of Angiotensin-Converting Enzyme (ACE) inhibitors, such as enalapril (Enalapril) or lisinopril (Lisinopril), in the management of patients with aortic regurgitation?

ACE Inhibitors in Aortic Regurgitation

ACE inhibitors have a clear role in aortic regurgitation when hypertension or heart failure is present, but their benefit in normotensive asymptomatic patients with preserved LV function remains unproven and they should not be routinely prescribed in this setting. 1

Established Indications for ACE Inhibitors

Chronic Severe AR with Heart Failure

• ACE inhibitors are the treatment of choice when surgery is contraindicated or in cases with persistent postoperative LV dysfunction. 1
• In a large cohort study of 2,266 patients with AR (45% with LV systolic dysfunction), ACE inhibitor/ARB therapy reduced the composite endpoint of death or hospitalization due to heart failure (adjusted HR 0.68,95% CI 0.54-0.87). 1, 2
• All-cause mortality was significantly reduced with ACE inhibitor/ARB use (adjusted HR 0.56,95% CI 0.64-0.89). 2

Hypertension Management

• In asymptomatic patients with high blood pressure (systolic BP >140 mmHg), antihypertensive treatment with vasodilators such as ACE inhibitors or dihydropyridine calcium channel blockers is warranted. 1, 3
• ACE inhibitors reduce afterload, diminish regurgitant volume, and increase effective stroke volume through their vasodilatory effects. 1

Patients Unfit for Surgery

• Pharmacological management plays an important role in selected AR patients with hypertension or those at prohibitive surgical risk. 1
• The greatest benefit has been noted in comorbid patients who cannot undergo valve replacement. 1

Unproven Indications

Asymptomatic Patients Without Hypertension

• The role of vasodilators in asymptomatic patients without high blood pressure to delay surgery is unproven. 1
• Despite theoretical benefits, these have not been consistently translated into clinical endpoints. 1
• Studies show mixed results: quinapril reduced LV mass and increased LVEF, while enalapril only improved LV end-diastolic diameter. 1
• Evangelista et al. reported no delay or reduction in aortic valve surgery in patients with severe AR and preserved LV function treated with either enalapril or nifedipine. 1

Vasodilator Therapy Considerations

• Vasodilator therapy may be considered only if systolic hypertension is present or LV cavity size is enlarged. 4
• Vasodilators are of unknown benefit and not indicated in patients with normal blood pressure or normal LV cavity size. 4

Special Populations

Marfan's Syndrome

• Enalapril has been used to delay aortic dilatation in patients with Marfan's syndrome, though beta-blockers remain the primary therapy for slowing aortic root progression. 1
• Whether the same beneficial effect occurs in patients with bicuspid aortic valves is not known. 1

Pediatric Patients

• Long-term ACE inhibitor therapy is effective in reducing both LV volume overload and LV hypertrophy in growing children with LV volume overload from aortic or mitral regurgitation. 5

Critical Pitfalls and Caveats

Not a Substitute for Surgery

• Medical management is not a substitute for aortic valve replacement (and root surgery where indicated). 1
• Surgery remains the definitive treatment for chronic severe aortic regurgitation. 4
• Surgical referral is indicated for patients who develop symptoms (dyspnea, angina, heart failure) or LV dysfunction (EF <50%). 4

Monitoring Requirements

• Echocardiographic surveillance every 1-2 years is recommended to detect progression to severe disease or development of LV dysfunction. 3, 4
• Clinical assessment should occur yearly, with more frequent imaging (every 3-6 months) if significant changes in LV ejection fraction or progressive LV dilatation occur. 3, 4

Drug Selection Considerations

• Avoid beta-blockers in severe AR as they prolong diastole and increase regurgitant volume, though they can be used cautiously in patients with severe LV dysfunction. 1, 3
• Dihydropyridine calcium channel blockers (nifedipine) are an alternative vasodilator option that may reduce the risk of LV systolic dysfunction in asymptomatic patients. 1