What medications are favored for treating Marfan's syndrome?

Medications for Marfan's Syndrome

Beta blockers or angiotensin receptor blockers (ARBs) in maximally tolerated doses are the first-line medications for patients with Marfan's syndrome to reduce the rate of aortic dilation. 1

First-Line Pharmacological Treatment Options

Beta Blockers

• Beta blockers have long been the foundation of medical therapy for Marfan syndrome to reduce heart rate, myocardial contractility, and slow aortic root growth 1
• Propranolol was the first beta blocker shown to be effective in a landmark open-label randomized study, demonstrating reduced aortic root growth rate (0.023 vs 0.084 per year) and fewer clinical events compared to no treatment over a 10-year follow-up period 2
• Beta blockers are recommended in maximally tolerated doses unless contraindicated 1

Angiotensin Receptor Blockers (ARBs)

• ARBs (particularly losartan) have been shown to be as effective as beta blockers in reducing aortic dilation rates 1
• Losartan was initially shown to prevent aneurysm formation in mouse models of Marfan syndrome 1
• In a small, non-randomized open-label study of children with Marfan syndrome who had previously experienced rapid aortic root growth, ARBs dramatically slowed aortic root growth 1
• Randomized trials comparing ARBs to beta blockers found no significant difference in aortic root growth rates or clinical events between treatment groups 3

Combination Therapy

• The combination of a beta blocker and an ARB in maximally tolerated doses is reasonable to reduce the rate of aortic dilation (Class 2a recommendation) 1
• Multiple trials have shown that adding an ARB to beta blocker therapy led to a reduction in aortic root growth rates over 3-5 years of follow-up 1
• A meta-analysis confirmed slower aortic growth rates with combination therapy compared to monotherapy 1

Treatment Algorithm

1. Initial therapy: Start with either:

   • Beta blocker (e.g., propranolol, atenolol) titrated to maximally tolerated dose 1, 2
   • OR ARB (e.g., losartan) titrated to maximally tolerated dose 1, 3

2. Optimization:

   • If single agent is well-tolerated but aortic dilation continues, consider combination therapy with both a beta blocker and ARB 1
   • Titrate both medications to maximally tolerated doses 1

3. Monitoring:

   • Regular imaging of the aortic root with echocardiography, CT, or MRI to assess treatment efficacy 1
   • More frequent imaging for patients with rapid aortic growth, those approaching surgical thresholds, or when aortic diameter exceeds 4.5 cm 1

Important Considerations and Pitfalls

• Despite medical therapy, surgical intervention is still recommended when aortic root diameter reaches ≥5.0 cm (Class 1 recommendation) 1
• Surgery may be reasonable at smaller diameters (≥4.5 cm) in patients with risk factors for aortic dissection 1
• Medical therapy does not eliminate the risk of aortic dissection or the need for eventual surgery in many patients 4
• The primary goal of medical therapy is to slow the rate of aortic dilation, not to reverse existing dilation 1, 5
• Long-term studies show that both beta blockers and ARBs have similar efficacy in preventing aortic complications, making ARBs a useful alternative for patients who cannot tolerate beta blockers 3

Special Populations

• For children with Marfan syndrome, beta blocker treatment has been associated with reduced aortic growth rate (slowed by approximately 0.2 mm/year) 1
• Dose adjustments may be needed based on patient weight, particularly in pediatric populations 6
• Regular monitoring of blood pressure is essential to ensure adequate dosing of antihypertensive medications 1