RAAS inhibitors in patients undergoing transcatheter aortic valve implantation: insights from the EffecTAVI registry
Authors: Basile C , Mancusi C , Franzone A , Avvedimento M , Angellotti D , Castiello D S , Mariani A , Manzo R , De Luca N , Cirillo P , De Simone G , Esposito G 
Published: November 2023

Abstract

Background
Aortic Stenosis (AS) is the most common heart disease in western countries, with a prevalence that is increasing in tandem with life expectancy. Renin-angiotensin-aldosterone system (RAAS) activation participates to myocardial fibrosis and worse clinical consequences.

Purpose
The association between baseline treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and cardiovascular (CV) mortality was evaluated in hypertensive patients with severe AS undergoing transcatheter aortic valve implantation (TAVI).

Methods
We retrospectively examined hypertensive patients with AS who had undergone TAVI at 2-year follow-up. Univariable and multivariable Cox regression models were built according to baseline RAAS inhibitors (RAASi) therapy status and a second analysis was undertaken by categorizing patients in ARBs (n= 110), ACEi (n= 112) and other antihypertensive meds (n= 105). As a sensitivity analysis, survival-time data were converted to case-control data in order to conduct a case–control study nested in the observational study.

Results
The present analysis included 327 hypertensive patients with severe AS undergoing TAVI. During the 2-year follow-up 43 patients died for CV death. In univariable Cox regression, the rate of the 2-year CV mortality was significantly lower in patients taking RAASi at baseline (HR=0.44, 95% CI 0.23-0.81 p=0.009), however after multivariable adjustment for significant confounders baseline treatment with RAASi was no more significant. Patients were then grouped based on ARBs/ACEIs/other antihypertensive therapy (Figure 1). In the univariate regression analysis ARBs therapy was associated with 65% reduction in CV mortality (HR=0.35, 95% CI 0.15-0.78 p=0.011) significantly lower than other anti-hypertensive meds (figure 1). The results were confirmed in multivariate analysis adjusted for significant confounders (HR=0.34, 95% CI 0.14-0.85 p=0.021). To reduce the risk of bias and better evaluate the stability of the results, a case–control study nested in the observational study was performed. Based on preliminary analysis, patients exposed to ARBs were selected as the case group, those not exposed as the control group, matching controls and cases in a 1:1 manner and balancing for sex, chronic kidney disease, atrial fibrillation and type 2 diabetes mellitus. Multivariable logistic regression analyses were conducted to determine the possible risk factors for CV mortality. After adjusting for the effect of significant confounders, the use of ARBs was found to be associated with a significant reduced risk of CV mortality (OR 0.30, 95% CI 0.11 – 0.82, p=0.019) (Figure 2).

Conclusion
In patients with severe AS undergoing TAVI, baseline treatment with ARBs was associated with reduced risk of CV mortality over 2 years of follow-up compared to the use of other antihypertensive drugs. The results were also confirmed by the nested, balanced, case-control analysis.KM curves grouped for ACEI/ARBs/otherAdjusted odds-ratio in the nested case-c