Target versus sub-target dose of renin–angiotensin system inhibitors on survival in elderly patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis

BACKGROUND The efficiency of the target versus sub-target dose of renin–angiotensin system inhibitors(RASIs)in elderly patients with heart failure(HF)with reduced ejection fraction(HErEF)remains unclear.METHODS PubMed,Embase,and the Cochrane Central Register of Controlled Trials were searched from database inception through March 2022 for randomized controlled trials(RCTs)and observational studies considering the effect of the target versus sub-target dose of RASIs on survival in elderly patients(≥60 years)with HErEF.The primary outcome was all-cause mortality.The secondary outcomes were cardiac mortality,HF hospitalization,and the composite endpoint of mortality or HF hospitalization.A meta-analysis was conducted to generate combined hazard ratio(HR)and 95%CI.RESULTS Seven studies(two RCTs and five observational studies)enrolling 16,634 patients were included.A pooled analysis suggested that the target versus sub-target dose of RASIs led to lower rates of all-cause mortality(HR=0.92,95%CI:0.87–0.98,I2=21%)and cardiac mortality(HR=0.93,95%CI:0.85–1.00,I2=15%)but not reduced rates of HF hospitalization(HR=0.94,95%CI:0.88–1.01,I2=0)and the composite endpoint(HR=1.03,95%CI:0.91–1.15,I2=51%).However,the target dose of RASIs was associated with a similar primary outcome(HR=0.85,95%CI:0.64–1.14,I2=0)in a subgroup of very elderly patients>75 years of age.CONCLUSIONS Our analysis suggests that the target dose of RASIs has a better survival benefit in elderly patients with HFrEF compared to the sub-target dose of RASIs.However,the sub-target dose of RASIs is associated with a similar mortality rate in very elderly patients>75 years of age.Future high-quality and adequately powered RCTs are warranted.