Impact of RAS inhibitors on 2-year mortality and disease progression in chronic mitral regurgitation

Chronic mitral regurgitation (MR) is associated with adverse clinical outcomes, and the role of renin-angiotensin system inhibitors (RASI) in patients with MR remains uncertain. This study evaluated the association between RASI use patterns and 2-year all-cause mortality and disease progression in patients with primary MR (PMR) and secondary MR (SMR). This registry-based study included 3,297 patients with moderate-to-severe chronic MR from the China Valvular Heart Disease registry, including 955 with PMR and 2,342 with SMR. RASI use was assessed at baseline and during follow-up, and patients were categorized as always users, never users, or inconsistent users. The primary endpoint was 2-year all-cause mortality. The secondary endpoint was change in MR severity. Associations between RASI use and outcomes were assessed using multivariable Cox regression, propensity-score matching, and time-varying Cox analyses. Consistent RASI use was associated with lower 2-year all-cause mortality in both PMR and SMR. In multivariable Cox regression, never users had higher mortality risk than always users in both cohorts (PMR: HR 5.40, 95% CI 1.58–18.47, P = 0.007; SMR: HR 5.09, 95% CI 2.85–9.09, P < 0.001). Inconsistent users also had higher mortality risk than always users (PMR: HR 7.56, 95% CI 2.25–25.37, P = 0.001; SMR: HR 3.29, 95% CI 1.85–5.84, P < 0.001). Propensity-score-matched analyses showed broadly consistent results. Time-varying Cox analyses demonstrated directionally consistent associations in the overall cohort and SMR during selected follow-up intervals, whereas in PMR the interval-specific estimates were less stable and did not reach statistical significance. Consistent RASI use was also associated with improvement in MR severity, particularly in SMR and in patients without guideline-based indications for valvular intervention. In patients with moderate-to-severe chronic MR, consistent RASI use was associated with lower 2-year all-cause mortality and improvement in MR severity. These findings suggest that RASI therapy may have a role in optimized medical management for selected patients with chronic MR, particularly those with SMR or impaired/borderline LV function. Further prospective studies are needed to confirm whether RASI directly improves survival or delays MR progression. This study utilized data from the China Valvular Heart Disease (China-VHD) registry (NCT03484806).