Angiotensin Receptor Blocker After TAVR in Severe Aortic Stenosis With Left Ventricular Hypertrophy (ARBITAR)

Condition(s) studied

Investigational drug(s) / intervention(s)

Angiotensin Receptor Blocker (ARB): An oral angiotensin receptor blocker - candesartan, losartan, or valsartan - is administered to the experimental group and, as a principle, up-titrated toward the target daily dose, with initiation at a lower starting dose permitted based on clinical need. Doses are: candesartan 4-8 mg once daily titrated to 32 mg once daily; losartan 25-50 mg once daily titrated to 50-150 mg once daily; valsartan 20-40 mg once daily titrated to 160 mg twice daily. Treatment is continued for up to 24 months. Up-titration is considered when all of the following are met: standing systolic blood pressure ≥90 mmHg, no symptoms of hypotension, serum creatinine \<2.0 mg/dL or \<50% increase from baseline, and serum potassium \<5.5 mmol/L. If serum potassium exceeds 6.0 mmol/L, the ARB is discontinued and resumed at a low dose once potassium returns below 5.5 mmol/L.

Study summary

This is a multicenter, prospective, open-label, randomized, investigator-initiated trial evaluating whether angiotensin receptor blocker (ARB) therapy improves clinical outcomes in patients with severe aortic stenosis (AS) and left ventricular hypertrophy (LVH) who have undergone transcatheter aortic valve replacement (TAVR).

Severe AS imposes chronic pressure overload on the left ventricle, leading to LVH as a compensatory response. While initially adaptive, sustained LVH promotes myocardial fibrosis, reduced ventricular compliance, and impaired cardiac function. LVH that persists after valve replacement is associated with increased morbidity and mortality, including a higher risk of heart failure. Blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACEi) or ARBs has been proposed as a strategy to attenuate adverse left ventricular remodeling after valve replacement by inhibiting angiotensin II-mediated hypertrophic and fibrotic signaling. However, evidence in TAVR patients with LVH remains limited, and a small randomized trial of an ACEi reported drug discontinuation in approximately 10% of patients due to dry cough. The ARBITAR trial therefore evaluates the clinical efficacy of an ARB in this population.

A total of 632 patients with symptomatic severe AS and LVH who have successfully undergone TAVR within the prior 30 days will be randomized 1:1 to receive an ARB (experimental group) or no ARB (control group), stratified by site and sex. Assigned treatment is continued for up to 24 months, with follow-up visits at 1, 6, 12, and 24 months. In the experimental group, the ARB (candesartan, losartan, or valsartan) is up-titrated toward a target dose. ACE inhibitors, direct renin inhibitors, and angiotensin receptor/neprilysin inhibitors are prohibited in both groups.

The primary endpoint is the composite of all-cause death or admission for heart failure over 2 years. Secondary endpoints include the individual components of the primary endpoint and other clinical events, as well as echocardiographic measures, NT-proBNP, NYHA functional class, and KCCQ-12 score. The primary analysis follows the intention-to-treat principle.

Eligibility

Primary outcome measure(s)

• Composite of all-cause death or admission for heart failure — From randomization to 2 years
  Time to the first occurrence of either all-cause death or admission for heart failure. Admission for heart failure is defined per VARC-3 criteria as hospitalization of at least 24 hours for new or worsening heart failure that is confirmed by signs and symptoms together with diagnostic testing and requires intravenous pharmacologic therapy or mechanical heart failure therapies.

Trial sites (1)

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