(VP061) IMPACT OF SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS ON QUALITY OF LIFE IN HEART FAILURE ACROSS THE EJECTION FRACTION SPECTRUM: SYSTEMATIC REVIEW AND META-ANALYSIS

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce hospitalizations in heart failure (HF) patients across the spectrum of ejection fraction, but no study has comprehensively explored their impact on quality of life (QoL). We aimed to explore the QoL impact of SGLT2i in HF across the spectrum of ejection fraction and over time.

METHODS AND RESULTS: We searched MEDLINE, EMBASE, and CENTRAL from 2019 (when the first SGLT2i HF trial was published) to February 2022. We included placebo-controlled randomized controlled trials (RCTs) enrolling HF patients that evaluated QoL as an outcome. Two reviewers independently assessed studies for eligibility, extracted data, and assessed risk of bias (RoB) using the Cochrane RoB 2 tool and certainty of evidence using GRADE. The primary outcomes were mean difference in disease-specific QoL using the 12-item or 23-item Kansas City Cardiomyopathy Questionnaire [KCCQ], Minnesota Living with Heart Failure Questionnaire [MLHFQ]) and their sub-scores. Secondary outcomes were the proportion of patients achieving a clinically-important improvement in QoL (e.g. 5-point improvement in KCCQ). We presented the primary outcome as a mean difference and the secondary outcome as a risk ratio (RR), and meta-analyzed them using a Mantel-Haenszel random-effects model, with Paule-Mandel estimator and the Hartung-Knapp variance estimate for dichotomous outcomes. We conducted subgroup analyses based on ejection fraction category, SGLT2i agent, and timing of QoL follow-up assessment.

From 1477 identified reports, we included 14 RCTs (n=23,361). All 14 trials were at overall low risk of bias. Mean age was 68, 34% were female, 67% were in New York Heart Association functional class 2, and median ejection fraction was 33%. All included RCTs reported QoL using the KCCQ-overall summary score, or its sub-scores. We rated certainty of evidence for the primary outcomes, as well as clinically-important improvement in KCCQ-total symptoms scores as high. Certainty of evidence was moderate for clinically-important improvement in KCCQ-overall summary score and clinical summary score due to inconsistency between studies. For the KCCQ-overall summary score, SGLT2 inhibitors improved mean scores (mean difference 2.0, 95% confidence interval (CI) 1.6-2.5) and the proportion of patients achieving a clinically-important improvement (risk ratio 1.14, 95% CI 1.02-1.28, 6.2% absolute risk increase [number needed to treat=17]). Similar improvements were observed in KCCQ clinical summary and total symptom sub-scores, and across all subgroups and timeframes.

Conclusion: SGLT2 inhibitors consistently provide a clinically-important improvement in QoL among patients with HF, regardless of ejection fraction, with noticeable improvements seen as early as week 2.