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    Association between prediabetes and adverse outcomes in heart failure. Mai Linlin,Wen Weixing,Qiu Min,Liu Xiong,Sun Lichang,Zheng Haoxiao,Cai Xiaoyan,Huang Yuli Diabetes, obesity & metabolism AIMS:Patients with heart failure (HF) and with diabetes experienced significantly worse outcomes than those without diabetes. However, data on the prognostic impact of prediabetes in HF are inconclusive. This meta-analysis aimed to explore the association between prediabetes and the risk of all-cause mortality and adverse cardiac outcomes in patients with HF. MATERIALS AND METHODS:We searched multiple electronic databases (PubMed, Embase and Google Scholar) for relevant studies up to 31 March 2021. Studies were included for analysis if multivariable adjusted relative risks of adverse outcomes were reported in patients with prediabetes and with HF compared with those with normoglycaemia. Random-effects models were used to calculate the pooled hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS:Twelve studies comprising 28 643 patients with HF reported the risk of all-cause mortality and cardiac outcomes associated with prediabetes. The prevalence of prediabetes ranged from 9.6% to 37.2%. After a median follow-up duration of 2.3 years, patients with HF and with prediabetes were associated with an increased risk of all-cause mortality (HR 1.29, 95% CI 1.06-1.58), cardiovascular mortality (HR 1.59, 95% CI 1.09-2.32), HF hospitalization (HR 1.33, 95% CI 1.09-1.61), all-cause mortality and/or HF hospitalization (HR 1.22, 95% CI 1.01-1.47), as well as cardiovascular mortality and/or HF hospitalization (HR 1.21, 95% CI 1.07-1.37). CONCLUSIONS:Prediabetes is associated with a worse prognosis in patients with HF. Further risk stratification and effective treatment strategies are needed in patients with prediabetes and with HF to improve the prognosis. 10.1111/dom.14490
    Empagliflozin in Patients With Heart Failure, Reduced Ejection Fraction, and Volume Overload: EMPEROR-Reduced Trial. Packer Milton,Anker Stefan D,Butler Javed,Filippatos Gerasimos,Ferreira Joao Pedro,Pocock Stuart J,Sattar Naveed,Brueckmann Martina,Jamal Waheed,Cotton Daniel,Iwata Tomoko,Zannad Faiez, Journal of the American College of Cardiology BACKGROUND:Investigators have hypothesized that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert diuretic effects that contribute to their ability to reduce serious heart failure events, and this action is particularly important in patients with fluid retention. OBJECTIVES:This study sought to evaluate the effects of the SGLT2 inhibitor empagliflozin on symptoms, health status, and major heart failure outcomes in patients with and without recent volume overload. METHODS:This double-blind randomized trial compared the effects of empagliflozin and placebo in 3,730 patients with heart failure and a reduced ejection fraction, with or without diabetes. Approximately 40% of the patients had volume overload in the 4 weeks before study enrollment. RESULTS:Patients with recent volume overload were more likely to have been hospitalized for heart failure and to have received an intravenous diuretic agent in an outpatient setting in the previous 12 months, and to experience a heart failure event following randomization, even though they were more likely to be treated with high doses of a loop diuretic agent as an outpatient (all p < 0.001). When compared with placebo, empagliflozin reduced the composite risk of cardiovascular death or hospitalization for heart failure, decreased total hospitalizations for heart failure, and improved health status and functional class. Yet despite the predisposition of patients with recent volume overload to fluid retention, the magnitude of these benefits (even after 1 month of treatment) was not more marked in patients with recent volume overload (interaction p values > 0.05). Changes in body weight, hematocrit, and natriuretic peptides (each potentially indicative of a diuretic action of SGLT2 inhibitors) did not track each other closely in their time course or in individual patients. CONCLUSIONS:Taken together, study findings do not support a dominant role of diuresis in mediating the physiological changes or clinical benefits of SGLT2 inhibitors on the course of heart failure in patients with a reduced ejection fraction. (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977). 10.1016/j.jacc.2021.01.033
    Interplay of Mineralocorticoid Receptor Antagonists and Empagliflozin in Heart Failure: EMPEROR-Reduced. Ferreira João Pedro,Zannad Faiez,Pocock Stuart J,Anker Stefan D,Butler Javed,Filippatos Gerasimos,Brueckmann Martina,Jamal Waheed,Steubl Dominik,Schueler Elke,Packer Milton Journal of the American College of Cardiology BACKGROUND:Mineralocorticoid receptor antagonists (MRAs) and sodium glucose co-transporter 2 inhibitors favorably influence the clinical course of patients with heart failure and reduced ejection fraction. OBJECTIVES:This study sought to study the mutual influence of empagliflozin and MRAs in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction). METHODS:Secondary analysis that compared the effects of empagliflozin versus placebo in 3,730 patients with heart failure and a reduced ejection fraction, of whom 71% used MRAs at randomization. RESULTS:The effects of empagliflozin on the primary endpoint, on most efficacy endpoints, and on safety were similar in patients receiving or not receiving an MRA (interaction p > 0.20). For cardiovascular death, the hazard ratios for the effect of empagliflozin versus placebo were 0.82 (95% confidence interval [CI]: 0.65 to 1.05) in MRA users and 1.19 (95% CI: 0.82 to 1.71) in MRA nonusers (interaction p = 0.10); a similar pattern was seen for all-cause mortality (interaction p = 0.098). Among MRA nonusers at baseline, patients in the empagliflozin group were 35% less likely than those in the placebo group to initiate treatment with an MRA following randomization (hazard ratio: 0.65; 95% CI: 0.49 to 0.85). Among MRA users at baseline, patients in the empagliflozin group were 22% less likely than those in the placebo group to discontinue treatment with an MRA following randomization (hazard ratio: 0.78; 95% CI: 0.64 to 0.96). Severe hyperkalemia was less common in the empagliflozin group. CONCLUSIONS:In EMPEROR-Reduced, the use of MRAs did not influence the effect of empagliflozin to reduce adverse heart failure and renal outcomes. Treatment with empagliflozin was associated with less discontinuation of MRAs. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977). 10.1016/j.jacc.2021.01.044