In an adult without contraindications, especially with Marfan syndrome, which angiotensin‑II receptor blocker is preferred for slowing thoracic aortic aneurysm growth?

Best ARB for Thoracic Aortic Aneurysm

Losartan is the preferred angiotensin receptor blocker for thoracic aortic aneurysms, particularly in Marfan syndrome, as it is the only ARB with specific guideline recommendations and mechanistic evidence showing unique AT2 receptor-mediated protective effects. 1, 2

Why Losartan is Preferred

Guideline-Specific Recommendation

• The 2010 ACC/AHA guidelines specifically name losartan as reasonable for patients with Marfan syndrome to reduce the rate of aortic dilatation (Class IIa, Level of Evidence B). 1
• The 2022 ACC/AHA guidelines recommend either a beta blocker or an ARB in maximally tolerated doses, with losartan being the ARB with the strongest evidence base. 1
• Recent 2024 Mayo Clinic guidelines confirm that losartan is the ARB with demonstrated efficacy through transforming growth factor-β inhibition. 1

Unique Mechanistic Advantage

• Losartan works through a dual mechanism that other ARBs may not replicate: it blocks AT1 receptors while simultaneously allowing protective AT2 receptor signaling. 3
• This AT2 receptor stimulation antagonizes ERK (extracellular signal-regulated kinase) activation, which is crucial for preventing aortic wall degeneration. 3
• The inverse agonist activity of certain ARBs (like candesartan) appears important, but losartan remains the most studied agent with proven clinical benefit. 4

Evidence Base

• Losartan prevented aneurysm formation in mouse models of Marfan syndrome and dramatically slowed aortic root growth in preliminary human studies. 1, 2
• In randomized trials, losartan showed equivalent efficacy to beta blockers in reducing aortic root growth rates. 1, 2
• ACE inhibitors (like enalapril) were less effective than losartan because they block both AT1 and AT2 receptors, eliminating the protective AT2 signaling. 3

Dosing Strategy

• Start losartan and titrate to maximally tolerated doses (typically 50-100 mg daily, though specific dosing should achieve adequate blood pressure control). 1, 2
• Target blood pressure should be reduced to the lowest tolerated level: <140/90 mmHg for patients without diabetes, <130/80 mmHg for those with diabetes or chronic kidney disease. 5

Combination Therapy Consideration

• Adding losartan to beta blocker therapy is reasonable if aortic dilation continues on monotherapy (Class 2a recommendation). 1, 2
• Multiple trials showed that combination therapy (beta blocker + ARB) reduced aortic root growth rates over 3-5 years compared to monotherapy. 1, 2
• Meta-analysis confirmed slower aortic growth rates with combination therapy, with an estimated 50% reduction in annual growth rate. 1

Critical Caveats

Other ARBs Lack Specific Evidence

• While class effect might be assumed, only losartan has been specifically studied and recommended in guidelines for thoracic aortic aneurysms. 1
• Valsartan showed reduction in aortic dissection incidence in the Jikei Heart Study, but this was a secondary finding in a general hypertensive population, not specific to aneurysm management. 1
• Recent research suggests that the inverse agonist properties of ARBs may differ, with candesartan showing benefit but neutral antagonists failing to prevent aortic progression. 4

Medical Therapy Does Not Eliminate Surgical Need

• Despite optimal medical therapy with losartan, surgical intervention remains necessary when aortic root diameter reaches ≥5.0 cm (Class 1 recommendation). 1, 2
• Surgery may be indicated at ≥4.5 cm in patients with additional risk factors (family history of dissection, rapid growth >0.5 cm/year, or desire for pregnancy). 1
• The goal of losartan is to slow progression, not reverse existing dilation. 2

Avoid Common Pitfall

• Do not use ACE inhibitors as a substitute for ARBs in this indication, as they block both AT1 and AT2 receptors, eliminating the protective AT2-mediated effects that make losartan superior. 6, 3