The Impact of Renin-Angiotensin-Aldosterone System Blockade on Heart Failure Outcomes and Mortality in Patients Identified to Have Aortic Regurgitation: A Large Population Cohort Study

Study Questions:

Does renin-angiotensin-aldosterone system (RAAS) inhibition impact outcomes in patients with moderate or worse aortic insufficiency (AI)?


This was a retrospective cohort study of patients with at least moderate AI enrolled into the Ninewells Hospital echocardiographic database in Scotland between 1993-2008. Patients were categorized as either taking a RAAS inhibitor (angiotensin-converting enzyme [ACE] inhibitor or angiotensin-receptor blocker [ARB]) or not during the period of follow-up. The primary outcome of interest was all-cause mortality in the two groups compared using Cox regression (hazard ratio [95% confidence interval] provided). Secondary outcomes included cardiovascular (CV) events (CV death/hospitalization) and AI events (heart failure hospitalization, heart failure death, or aortic valve replacement).


Patients taking a RAAS inhibitor (n = 876, 39%) were younger (median age 75 years for controls vs. 72 years for RAAS inhibition) and more likely to be on a diuretic, beta-blocker, calcium channel antagonist, nitrate, and statin than controls (n = 1,390, 61%, all p < 0.0001). The proportion of patients categorized as having left ventricular (LV) impairment was similar between the groups (p = 0.38). Over a mean ± standard deviation 4.4 ± 3.7 years of follow-up, there were 582 deaths (127 [22%] on a RAAS inhibitor), 1,069 CV events (344 [32%] on a RAAS inhibitor), and 354 AI events (155 [44%] on a RAAS inhibitor). The use of a RAAS inhibitor was associated with a 44% reduction in all-cause mortality (HR 0.56 [0.46-0.68]), a 23% reduction in CV events (HR 0.77 [0.67-0.89]), and a 26% reduction in AI related events (HR 0.74 [0.54-0.87]). Mortality was not different when RAAS use was stratified by LV function, but patients on RAAS inhibitors with a LV internal dimension <60 mm had an HR for death of 0.77 [0.67-0.90] compared with 0.52 [0.32-0.86] for patients on RAAS inhibitors with LV dimensions >60 mm.


The authors concluded that patients with AI in this cohort had improved outcomes when treated with RAAS inhibitors.


Clinical data for guiding medical management of patients with AI are lacking, especially those with normal LV ejection fractions. This longitudinal cohort study suggests that outcomes are better in patients treated with ACE inhibitors/ARBs. While propensity matching was employed, this study has several limitations (acknowledged by the authors) that are inherent to unblinded, nonrandomized-controlled analyses with ICD-9 categorization of outcomes. Since details on mean ejection fraction, LV diastolic dimension, and frequency of practitioner follow-up are not provided, it is possible that patients in the RAAS inhibitor group were ‘healthier’ or had better access to medical care, allowing for improved outcomes. I also found the cumulative incidence of valve interventions (2.7%) to be low for the burden of cardiac events reported over 4 years of follow-up (47% died or were hospitalized). Regardless, this trial lends some support to RAAS inhibition in patients with AI. Selecting a RAAS inhibitor over another agent seems especially reasonable in patients requiring diuretics (suggesting high RAAS activity) or those with systemic hypertension. A multicenter study of AI management is truly needed.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Hypertension

Keywords: Follow-Up Studies, Proto-Oncogene Proteins, Scotland, Mineralocorticoid Receptor Antagonists, Diuretics, Heart Failure, Renin-Angiotensin System, Confidence Intervals, Diastole, Hypertension

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