A prospective, double-blinded, randomized trial of Ramipril in asymptomatic aortic stenosis: the RIAS trial

Abstract

Background: Angiotensin‐converting‐enzyme (ACE) inhibitors have potential benefit through positive remodeling in aortic stenosis (AS) but no prospective clinical trials have been carried out. We hypothesized that ramipril would lead to regression of LV mass in patients with AS and potentially slow disease progression. Methods: We conducted a prospective, randomized, double‐blind, placebo‐controlled trial focusing on cardiac physiology. 100 patients with moderate or severe asymptomatic AS were randomized to either ramipril 10mg daily (n=50) or placebo (n=50) for a year. Patients underwent assessment at baseline, six and twelve months, consisting of CMR scanning to determine LV mass, function, strain, perfusion and T1 values; echocardiography and exercise testing. Results: Data was available in 78 patients for the primary endpoint (LV mass) at 12 months. There was a reduction in LV mass in the ramipril group (mean change ±standard deviation: ‐2.0±1.7g at 6 months; ‐3.9±2.1g at 12 months, compared to an increase in LV mass in the placebo group: +2.0±1.5g at 6 months; +4.5±2.0g at twelve months (mean difference at 12 months 8.4g [5%]; p=0.006; Figure 1). There was a trend towards reduction in valve area (‐0.2cm2, p=0.067) and increase in peak aortic velocity (+0.1m/sec, p=0.056) in the placebo group, and fewer deaths in the ramipril group after completion of the trial (p=0.074). (figure presented) Conclusion: Ramipril is safe in moderate and severe asymptomatic AS and leads to a small but significant reduction in LV mass at 12 months. There were trends towards slower progression of valvular stenosis and fewer deaths post‐trial in the treatment group. A larger multi‐center clinical outcome trial over a longer period is required to determine whether this translates into clinical benefit.