Impact of renin-angiotensin system inhibitors on long-term clinical outcomes of patients with rheumatic heart disease

Abstract

Aims: Rheumatic heart disease (RHD) remains a major global health problem. Renin-angiotensin-aldosterone system inhibitors (RAASi) are commonly administered in the treatment of cardiovascular disease, but its role in RHD patients is still limited. We performed a retrospective study to determine the effect of RAASi on long-term outcomes for RHD patients.

Methods and results: A 1:1 propensity score matching was implemented to balance baseline characteristics between groups RAASi and non-RAASi. Cox proportional hazards regression model was used to investigate the associations of RAASi with the risks of all-cause mortality, cardiovascular death (CVD), and cerebrovascular death. Binary logistic regression analysis was used to evaluate the associations of RAASi with the risks of 1, 3, and 5 year heart failure (HF) rehospitalization, new-onset atrial fibrillation (AF), and new-onset stroke. A total of 734 RHD patients were enrolled as study participants; nearly half of these participants had combined valve damage (54.4%), worse New York Heart Association functional class status (III and IV, 55.2%), surgical treatment (54.2%), and AF (65.0%). After propensity score matching, 514 RHD patients were finally analysed. RAASi treatment was associated with decreased risks of all-cause mortality [adjusted hazard ratio (HR) = 0.52, 95% confidence interval (CI): 0.37-0.73, P < 0.001], CVD (adjusted HR = 0.48, 95% CI: 0.30-0.76, P = 0.002), and cerebrovascular death (adjusted HR = 0.22, 95% CI: 0.08-0.60, P = 0.003). Further subgroup analysis showed that RAASi treatment was associated with decreased risks of all-cause mortality (adjusted HR = 0.50, 95% CI: 0.31-0.79, P = 0.004), CVD (adjusted HR = 0.48, 95% CI: 0.25-0.91, P = 0.025), and cerebrovascular death (adjusted HR = 0.19, 95% CI: 0.05-0.65, P = 0.008) in RHD patients without surgical treatment, and better effect was observed in RHD patients with surgical treatment on the risks of all-cause mortality (adjusted HR = 0.47, 95% CI: 0.26-0.85, P = 0.012) and CVD (adjusted HR = 0.43, 95% CI: 0.21-0.90, P = 0.024) except cerebrovascular death (adjusted HR = 0.52, 95% CI: 0.08-3.36, P = 0.491). RAASi treatment was associated with decreased HF rehospitalization risk of 1 year [adjusted odds ratio (OR) = 0.38, 95% CI: 0.23-0.61, P < 0.001], 3 year (adjusted OR = 0.43, 95% CI: 0.28-0.68, P < 0.001), and 5 year (adjusted OR = 0.48, 95% CI: 0.30-0.77, P = 0.002) as well as new-onset AF risk (adjusted OR = 0.38, 95% CI: 0.21-0.68, P = 0.001). RAASi treatment had nothing to do with new-onset stroke risk (adjusted OR = 0.80, 95% CI: 0.47-1.38, P = 0.428).

Conclusion: Renin-angiotensin-aldosterone system inhibitor treatment was significantly associated with decreased risks of mortality, HF rehospitalization, and new-onset AF in RHD patients in median 5.9 year follow-up.

Keywords: Atrial fibrillation; Heart failure; Renin-angiotensin system inhibitors; Rheumatic heart disease; Stroke; Survival.