Aims The EMPERIAL (Effect of EMPagliflozin on ExeRcise ability and HF symptoms In patients with chronic heArt faiLure) trials evaluated the effects of empagliflozin on exercise ability and patient-reported outcomes in heart failure (HF) with reduced and preserved ejection fraction (EF), with and without type 2 diabetes (T2D), reporting, for the first time, the effects of sodium-glucose co-transporter-2 inhibition in HF with preserved EF (HFpEF). Methods and results HF patients with reduced EF (HFrEF) (≤40%,N = 312, EMPERIAL-Reduced) or preserved EF (>40%,N = 315, EMPERIAL-Preserved), with and without T2D, were randomized to empagliflozin 10 mg or placebo for 12 weeks. The primary endpoint was 6-minute walk test distance (6MWTD) change to Week 12. Key secondary endpoints included Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) and Chronic Heart Failure Questionnaire Self-Administered Standardized format (CHQ-SAS) dyspnoea score. 6MWTD median (95% confidence interval) differences, empagliflozin vs. placebo, at Week 12 were −4.0 m (−16.0, 6.0;P = 0.42) and 4.0 m (−5.0, 13.0;P = 0.37) in EMPERIAL-Reduced and EMPERIAL-Preserved, respectively. As the primary endpoint was non-significant, all secondary endpoints were considered exploratory. Changes in KCCQ-TSS and CHQ-SAS dyspnoea score were non-significant. Improvements with empagliflozin in exploratory pre-specified analyses of KCCQ-TSS responder rates, congestion score, and diuretic use in EMPERIAL-Reduced are hypothesis generating. Empagliflozin adverse events were consistent with those previously reported. Conclusion The primary outcome for both trials was neutral. Empagliflozin was well tolerated in HF patients, with and without T2D, with a safety profile consistent with that previously reported in T2D. Hypothesis-generating improvements in exploratory analyses of secondary endpoints with empagliflozin in HFrEF were observed.

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Background This is an ongoing follow-up study (NCT02723773) evaluating persistence of efficacy and immune responses for six additional years in adults vaccinated with the glycoprotein E (gE)-based adjuvanted recombinant zoster vaccine (RZV) at ≥50 years of age in two pivotal efficacy trials (ZOE-50/70). The present interim analysis was performed after ≥2 additional years of follow-up (between 5.1 and 7.1 years [mean] post-vaccination) and includes partial data for year (Y)8 post-vaccination. Methods Annual assessments were performed for efficacy against herpes zoster (HZ) from Y6 post-vaccination onwards, and for anti-gE antibody concentrations and gE-specific CD4[2+] T-cell (expressing ≥2 of four assessed activation markers) frequencies from Y5 post-vaccination onwards. Results Of 7413 participants enrolled for the long-term efficacy assessment, 7277 (mean age at vaccination: 67.2 years), 813, and 108 were included in the cohorts for the evaluation of efficacy, humoral immune responses, and cell-mediated immune responses, respectively. Efficacy of RZV against HZ through this interim analysis was 84.0% (95% confidence interval [CI]: 75.9-89.8) from the start of this follow-up study and 90.9% (95%CI: 88.2-93.2) from vaccination in ZOE-50/70. Annual vaccine efficacy estimates were >84% for each year since vaccination and remained stable during this follow-up study through the interim analysis. Anti-gE antibody geometric mean concentrations and median frequencies of gE-specific CD4[2+] T cells had plateaued throughout this follow-up study up to the interim analysis, at ~6-fold above pre-vaccination levels. Conclusion Efficacy against HZ and immune responses to RZV remained high, suggesting that the clinical benefit of RZV in older adults is sustained for at least seven years post-vaccination.

When the adjuvanted HZ subunit vaccine candidate was coadministered with a quadrivalent seasonal influenza vaccine, no interference in the immune responses were observed, and no safety concerns were identified.