Large traditional clinical trials suggest that sodium-glucose co-transporter 2 inhibitors improve symptoms in patients with heart failure and reduced ejection fraction (HFrEF) and in patients with heart failure and preserved ejection fraction (HFpEF). In the midst of the Coronavirus Disease 2019 pandemic, we sought to confirm these benefits in a new type of trial that was patient centered and conducted in a completely remote fashion. In the CHIEF-HF trial ( NCT04252287 ), 476 participants with HF, regardless of EF or diabetes status, were randomized to 100 mg of canagliflozin or placebo. Enrollment was stopped early due to shifting sponsor priorities, without unblinding. The primary outcome was change in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ TSS) at 12 weeks. The 12-week change in KCCQ TSS was 4.3 points (95% confidence interval, 0.8-7.8; P = 0.016) higher with canagliflozin than with placebo, meeting the primary endpoint. Similar effects were observed in participants with HFpEF and in those with HFrEF and in participants with and without diabetes, demonstrating that canagliflozin significantly improves symptom burden in HF, regardless of EF or diabetes status. This randomized, double-blind trial, conducted without in-person interactions between doctor and patient, can serve as a model for future all-virtual clinical trials.
Subject(s)COVID-19 , Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Ventricular Dysfunction, Left , Canagliflozin/pharmacology , Canagliflozin/therapeutic use , Heart Failure/diagnosis , Heart Failure/drug therapy , Humans , Patient-Centered Care , Quality of Life , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Stroke Volume
BACKGROUND: COVID-19 can lead to multiorgan failure. Dapagliflozin, a SGLT2 inhibitor, has significant protective benefits for the heart and kidney. We aimed to see whether this agent might provide organ protection in patients with COVID-19 by affecting processes dysregulated during acute illness. METHODS: DARE-19 was a randomised, double-blind, placebo-controlled trial of patients hospitalised with COVID-19 and with at least one cardiometabolic risk factor (ie, hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease). Patients critically ill at screening were excluded. Patients were randomly assigned 1:1 to dapagliflozin (10 mg daily orally) or matched placebo for 30 days. Dual primary outcomes were assessed in the intention-to-treat population: the outcome of prevention (time to new or worsened organ dysfunction or death), and the hierarchial composite outcome of recovery (change in clinical status by day 30). Safety outcomes, in patients who received at least one study medication dose, included serious adverse events, adverse events leading to discontinuation, and adverse events of interest. This study is registered with ClinicalTrials.gov, NCT04350593. FINDINGS: Between April 22, 2020 and Jan 1, 2021, 1250 patients were randomly assigned with 625 in each group. The primary composite outcome of prevention showed organ dysfunction or death occurred in 70 patients (11·2%) in the dapagliflozin group, and 86 (13·8%) in the placebo group (hazard ratio [HR] 0·80, 95% CI 0·58-1·10; p=0·17). For the primary outcome of recovery, 547 patients (87·5%) in the dapagliflozin group and 532 (85·1%) in the placebo group showed clinical status improvement, although this was not statistically significant (win ratio 1·09, 95% CI 0·97-1·22; p=0·14). There were 41 deaths (6·6%) in the dapagliflozin group, and 54 (8·6%) in the placebo group (HR 0·77, 95% CI 0·52-1·16). Serious adverse events were reported in 65 (10·6%) of 613 patients treated with dapagliflozin and in 82 (13·3%) of 616 patients given the placebo. INTERPRETATION: In patients with cardiometabolic risk factors who were hospitalised with COVID-19, treatment with dapagliflozin did not result in a statistically significant risk reduction in organ dysfunction or death, or improvement in clinical recovery, but was well tolerated. FUNDING: AstraZeneca.
Subject(s)Benzhydryl Compounds/administration & dosage , COVID-19/complications , Cardiometabolic Risk Factors , Glucosides/administration & dosage , Multiple Organ Failure/prevention & control , Sodium-Glucose Transporter 2 Inhibitors/administration & dosage , Aged , Double-Blind Method , Female , Humans , Male , Middle Aged , Multiple Organ Failure/complications , Treatment Outcome
OBJECTIVES: This study sought to determine whether the increased use of telehealth was associated with a difference in outcomes for outpatients with heart failure. BACKGROUND: The COVID-19 pandemic led to dramatic changes in the delivery of outpatient care. It is unclear whether increased use of telehealth affected outcomes for outpatients with heart failure. METHODS: In March 2020, a large Midwestern health care system, encompassing 16 cardiology clinics, 16 emergency departments, and 12 hospitals, initiated a telehealth-based model for outpatient care in the setting of the COVID-19 pandemic. A propensity-matched analysis was performed to compare outcomes between outpatients seen in-person in 2018 and 2019 and via telemedicine in 2020. RESULTS: Among 8,263 unique patients with heart failure with 15,421 clinic visits seen from March 15 to June 15, telehealth was employed in 88.5% of 2020 visits but in none in 2018 or 2019. Despite the pandemic, more outpatients were seen in 2020 (n = 5,224) versus 2018 and 2019 (n = 5,099 per year). Using propensity matching, 4,541 telehealth visits in 2020 were compared with 4,541 in-person visits in 2018 and 2019, and groups were well matched. Mortality was similar for telehealth and in-person visits at both 30 days (0.8% vs 0.7%) and 90 days (2.9% vs 2.4%). Likewise, there was no excess in hospital encounters or need for intensive care with telehealth visits. CONCLUSIONS: A telehealth model for outpatients with heart failure allowed for distanced encounters without increases in subsequent acute care or mortality. As the pressures of the COVID-19 pandemic abate, these data suggest that telehealth outpatient visits in patients with heart failure can be safely incorporated into clinical practice.