Effects and safety of SGLT2 inhibitors compared to placebo in patients with heart failure: A systematic review and meta-analysis

Background: Heart failure (HF) prognosis without therapy is poor, however introduction of a range of drugs has improved it. We aimed to perform a systematic review on the effects and safety of sodium-glucose transporter 2 inhibitors (SGLT2i) in HF patients. Methods: We carried out a systematic review of randomized controlled trials (RCTs) on SGLT2i compared to placebo for HF patients. We searched in PubMed, Scopus, Web of Science and EMBASE, with no language restriction, from inception to 31 August 2020. We included nine RCTs comprising three arms (empagliflozin, dapagliflozin and placebo). Effects sizes for continuous variables were expressed as mean differences (MDs) and 95% confidence intervals (CIs). Effects sizes for dichotomous variables were expresses as risk ratio (RR) and 95% CIs. We used random-effect models with the inverse variance method. We performed subgroup meta-analyses by intervention drug and follow-up period. Results: SGLT2i significantly reduced all-cause mortality (RR: 0.88, 95%CI 0.79–0.98, I2 = 0%), cardiovascular mortality (RR: 0.87, 95%CI 0.77–0.99, I2 = 0%), HF hospitalization (RR: 0.73, 95%CI 0.66–0.81, I2 = 0%) and emergency room visits due to HF (RR: 0.40, 95%CI 0.21–0.76, I2 = 0%), as well as composite outcomes including the previous ones. Besides, it significantly improved the score of the Kansas City Cardiomyopathy Questionnaire (KCCQ, MD: 1.70, 95%CI 1.67–1.73, I2 = 54%). SGLT2i reduced any serious adverse events, blood pressure and weight. However, it increased hematocrit and creatinine. The meta-analysis of RCTs of > 12 weeks of follow-up showed that SGTL2i significantly reduced NT-proBNP. Conclusions: SGLT2i showed to improve critical outcomes in HF patients, and it is apparently safe.