Medical treatment of heart failure with RAS inhibitors and beta blockers in aortic stenosis – association to long-term outcome after aortic valve replacement

There is a lack of robust data on optimal medical treatment of heart failure in patients with severe aortic stenosis, with no randomized controlled trials guiding treatment. To study the association between exposure to renin-angiotensin-aldosterone system (RAS) inhibitors or beta-blockers and outcome after aortic valve replacement in patients with aortic stenosis and heart failure. The study included all patients with heart failure undergoing aortic valve replacement for aortic stenosis in Sweden between 2008-2016 (n = 4668 patients). Exposure to treatment was assessed by continuous tracking of drug dispensations and outcome events were all-cause mortality and hospitalization for heart failure collected from national patient registries. After adjustment for age, sex, atrial fibrillation, hypertension, diabetes mellitus and prior myocardial infarction Cox regression analysis showed that RAS inhibition was associated with a lower risk of all-cause mortality in patients with reduced LV-EF (HR 0.58, 95% CI 0.51 - 0.65) and preserved LV-EF (HR 0.69, 95% CI 0.56 - 0.85). Beta-blockade was associated with a lower risk of all-cause mortality in patients with reduced LV-EF (HR 0.81, 95% CI 0.71–0.92), but not in preserved LV-EF (HR 0.87, 95% CI 0.69 - 1.10). There was no association between RAS inhibition or beta-blockade and the risk of hospitalization for heart failure. RAS inhibition was associated with lower all-cause mortality after valve replacement in patients with both reduced and preserved LV-EF. Beta-blockade was associated with lower all-cause mortality only in patients with reduced LV-EF.