Efficacy of medication therapy for patients with chronic kidney disease and heart failure with preserved ejection fraction: a systematic review and meta-analysis

BACKGROUND The prevalence and mortality of heart failure with preserved ejection fraction (HFpEF) are high in patients with chronic kidney disease (CKD). However, there is still a lack of recommendations for the medication therapy of these patients in the guideline so far. METHODS We conducted a systematic review and meta-analysis of all the studies assessing medication therapy for patients with CKD and HFpEF by July 21, 2021. Pooled analysis was performed using a random-effect model and the quality assessment was performed. In our research, we followed to the Preferred Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The meta-analysis was registered on PROSPERO. RESULTS We finally identified six studies, three of which were randomized controlled trials and the others were retrospective cohort studies. The results of meta-analysis including three retrospective cohort studies showed that renin-angiotensin system inhibitors had significantly reduced all-cause mortality by 14% (3 studies, 3816 patients, HR 0.86; 95% CI 0.79-0.95; I2 = 49%; P = 0.003), and all-cause hospitalization by 11% (2 studies, 2350 patients, HR 0.89; 95% CI 0.85-0.94; I2 = 0%; P < 0.00001) in patients with CKD and HFpEF. However, there was no significant reduction in the risk of hospitalization for heart failure (3 studies, 3816 patients, HR 0.88; 95% CI 0.75-1.04; I2 = 75%; P = 0.13). One of the studies focused on the sacubitril-valsartan showed that sacubitril-valsartan was associated with a reduced risk of hospitalization for heart failure and cardiovascular death (RR 0.79, 95% CI 0.66-0.95). The study focused on the carvedilol did not show a significant reduction in the risk of hospitalization for heart failure and cardiovascular death (HR 0.917, 95% CI 0.501-1.678). CONCLUSIONS For patients with CKD and HFpEF, renin-angiotensin system inhibitors is associated with significant benefits in all-cause mortality and all-cause hospitalization but has no significant effect on hospitalization for heart failure. The subgroup analysis of one RCT study focused on ARNI showed that although long-term treatment with sacubitril-valsartan may reduce the risk of hospitalization for heart failure and cardiovascular death, more studies are needed to confirm that.