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

backgroundChronic 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).

methodsThis 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.

resultsConsistent 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.

conclusionsIn 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.

trial registrationThis study utilized data from the China Valvular Heart Disease (China-VHD) registry (NCT03484806).