Is the use of renin–angiotensin system inhibitors in patients with aortic valve stenosis safe and of prognostic benefit? A systematic review and meta-analysis

Aortic valve stenosis (AVS) is associated with significant morbidity and mortality, especially in the presence of symptoms and echocardiographic signs of left ventricular remodelling (i.e. increase in left ventricular mass, left ventricular dilation, and systolic dysfunction). Renin-angiotensin system inhibitors (RASi) attenuate cardiac remodelling in various conditions, but the safety and efficacy of RASi in AVS is unsure. We performed a systematic review and meta-analysis to address these issues. We identified three smaller randomized clinical trials and five observational studies eligible for inclusion (PubMed, EMBASE, and Cochrane library search criteria: aortic stenosis, aortic valve, angiotensin-converting enzyme inhibitor in different combinations, published in English at any time up to 1 April 2016). Our analyses suggested that use of RASi was safe, with no observed increase in mortality risk [576/3389 patients receiving RASi vs. 1118/4384 controls died; relative risk 0.93 (95% confidence interval 0.78-1.11), P = 0.44]. Use of RASi was also observed to lower the risk of aortic valve replacement (AVR) surgery [67/2913 patients with RASi vs. 154/3666 controls underwent AVR; relative risk 0.68 (95% confidence interval 0.51-0.91), P = 0.01]. In current clinical practice (based on published literature; mainly observational studies), use of RASi appears to be safe in patients with AVS and may reduce the need for AVR, but the evidence is overall weak. Large-scale randomized clinical trials are warranted to address whether prescription of RASi to treatment-naïve patients may prevent disease progression, delay AVR surgery need, and lower the risk of mortality.