| 1. |
- Adamson, Carly, et al.
(författare)
-
Liver tests and outcomes in heart failure with reduced ejection fraction: findings from DAPA-HF.
- 2022
-
Ingår i: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 24:10, s. 1856-68
-
Tidskriftsartikel (refereegranskat)abstract
- Reflecting both increased venous pressure and reduced cardiac output, abnormal liver tests are common in patients with severe heart failure and are associated with adverse clinical outcomes. We aimed to investigate the prognostic significance of abnormal liver tests in ambulatory patients with heart failure with reduced ejection fraction (HFrEF), explore any treatment interaction between bilirubin and sodium-glucose cotransporter 2 (SGLT2) inhibitors and examine change in liver tests with SGLT2 inhibitor treatment.We explored these objectives in the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, with focus on bilirubin. We calculated the incidence of cardiovascular death or worsening heart failure by bilirubin tertile. Secondary cardiovascular outcomes were examined, along with the change in liver tests at the end-of-study visit. Baseline bilirubin was available in 4720 patients (99.5%). Participants in the highest bilirubin tertile (T3) have more severe HFrEF (lower left ventricular ejection fraction, higher N-terminal pro-B-type natriuretic peptide [NT-proBNP] and worse New York Heart Association class), had a greater burden of atrial fibrillation but less diabetes. Higher bilirubin (T3 vs. T1) was associated with worse outcomes even after adjustment for other predictive variables, including NT-proBNP and troponin T (adjusted hazard ratio for the primary outcome 1.73 [95% confidence interval 1.37-2.17], p < 0.001; and 1.52 [1.12-2.07], p = 0.01 for cardiovascular death). Baseline bilirubin did not modify the benefits of dapagliflozin. During follow-up, dapagliflozin had no effect on liver tests.Bilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of dapagliflozin in HFrEF. Dapagliflozin was not associated with change in liver tests.ClinicalTrials.gov NCT03036124.
|
|
| 2. |
- Heerspink, Hiddo J L, et al.
(författare)
-
A pre-specified analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial on the incidence of abrupt declines in kidney function.
- 2022
-
Ingår i: Kidney international. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 101:1, s. 174-184
-
Tidskriftsartikel (refereegranskat)abstract
- This pre-specified analysis of DAPA-CKD assessed the impact of sodium-glucose cotransporter 2 inhibition on abrupt declines in kidney function in high-risk patients based on having chronic kidney disease (CKD) and substantial albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial that had a median follow-up of 2.4 years. Adults with CKD (urinary albumin-to-creatinine ratio 200-5000 mg/g and estimated glomerular filtration rate 25-75 mL/min/1.73m2) were randomized to dapagliflozin 10 mg/day matched to placebo (2152 individuals each). An abrupt decline in kidney function was defined as a pre-specified endpoint of doubling of serum creatinine between two subsequent study visits. We also assessed a post-hoc analysis of investigator-reported acute kidney injury-related serious adverse events. Doubling of serum creatinine between two subsequent visits (median time-interval 100 days) occurred in 63 (2.9%) and 91 (4.2%) participants in the dapagliflozin and placebo groups, respectively (hazard ratio 0.68 [95% confidence interval 0.49, 0.94]). Accounting for the competing risk of mortality did not alter our findings. There was no heterogeneity in the effect of dapagliflozin on abrupt declines in kidney function based on baseline subgroups. Acute kidney injury-related serious adverse events were not significantly different and occurred in 52 (2.5%) and 69 (3.2%) participants in the dapagliflozin and placebo groups, respectively (0.77 [0.54, 1.10]). Thus, in patients with CKD and substantial albuminuria, dapagliflozin reduced the risk of abrupt declines in kidney function.
|
|
| 3. |
- Pollack, Charles V, et al.
(författare)
-
International Perspectives on the Impact of the COVID-19 Pandemic on Adherence to Prescribed Dual Antiplatelet Therapy : A Window Into Acute Cardiovascular Care.
- 2022
-
Ingår i: Critical Pathways in Cardiology. - : Ovid Technologies (Wolters Kluwer Health). - 1535-282X .- 1535-2811. ; 21:3, s. 114-122
-
Tidskriftsartikel (refereegranskat)abstract
- An international panel of expert clinicians and researchers in acute cardiac care was convened to review, describe, and contextualize their varied experiences delivering care and maintaining ongoing research during the first year of the COVID-19 pandemic and beyond. A proposed perspective from which care and outcomes could be viewed was the possibility that without routine follow-up and as-accustomed interactions with their care team, patients at risk of acute atherothrombotic events might be less adherent to prescribed antiplatelet medications. This might be manifested by more emergency coronary events or by an increased (and perhaps unidentifiable) incidence of out-of-hospital cardiovascular deaths related to patient anxiety about presenting to hospital during the pandemic. The experiences of the panel members were similar in many regards, which identified opportunities for improvement in cardiac care the next time there is a substantial disruption of usual practice. Regardless of geography or payor system, there was an identified need for better remote care platforms; but stronger infrastructure and consumer facility with remote care technology, improved provider-patient communication to help ensure adherence to primary and secondary prevention medications, and longer-term prescription fills and no-hassle refills on such medications. Profound disruptions in acute cardiovascular research highlighted the need for redundancy or back-up planning for teams engaged in time-sensitive research, to ensure both continuity of protocols and patient safety.
|
|
| 4. |
- Vaduganathan, Muthiah, et al.
(författare)
-
Time to Clinical Benefit of Dapagliflozin in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction : A Prespecified Secondary Analysis of the DELIVER Randomized Clinical Trial.
- 2022
-
Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 7:12, s. 1259-1263
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Dapagliflozin was recently shown to reduce cardiovascular death or worsening heart failure (HF) events in patients with HF with mildly reduced or preserved ejection fraction in the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial. Objective: To evaluate the time course of benefits of dapagliflozin on clinically relevant outcomes in this population. Design, Setting, and Participants: The DELIVER trial was a global phase 3 clinical trial that randomized patients with HF with mildly reduced or preserved ejection fraction to dapagliflozin or matching placebo. Inclusion criteria included symptomatic HF, left ventricular ejection fraction greater than 40%, elevated natriuretic peptide levels, and evidence of structural heart disease. In this prespecified secondary analysis of the DELIVER trial, to examine the timeline to onset of clinical benefit with dapagliflozin, hazard ratios (HR) and 95% CIs were iteratively estimated for the primary composite end point and worsening HF events alone with truncated data at every day postrandomization. Time to first and sustained statistical significance of dapagliflozin for these end points were then examined. Participants were enrolled from August 2018 to December 2020, and for this secondary analysis, data were analyzed from April to September 2022. Interventions: Dapagliflozin, 10 mg, once daily or matching placebo. Main Outcomes and Measures: The primary outcome was time to first occurrence of cardiovascular death or worsening HF (hospitalization for HF or urgent HF visit requiring intravenous HF therapies). Results: Overall, 6263 patients were randomized across 350 centers in 20 countries. Of 6263 included patients, 2747 (43.9%) were women, and the mean (SD) age was 71.7 (9.6) years. During a median (IQR) of 2.3 (1.7-2.8) years’ follow- up, 1122 primary end point events occurred, with an incidence rate per 100 patient-years of 8.7 (95% CI, 8.2-9.2). Time to first nominal statistical significance for the primary end point was 13 days (HR, 0.45; 95% CI, 0.20-0.99; P = .046), and significance was sustained from day 15 onwards. First and sustained statistical significance was reached for worsening HF events (HR, 0.45; 95% CI, 0.21-0.96; P = .04) by day 16 after randomization. Significant benefits for the primary end point and worsening HF events were sustained at 30 days, 90 days, 6 months, 1 year, 2 years, and final follow-up (primary end point: HR, 0.82; 95% CI, 0.73-0.92; worsening HF events: HR, 0.79; 95% CI, 0.69-0.91). Conclusions and Relevance: In the DELIVER trial, dapagliflozin led to early and sustained reductions in clinical events in patients with HF with mildly reduced or preserved ejection fraction with statistically significant reductions observed within 2 weeks of treatment initiation. Trial Registration: ClinicalTrials.gov Identifier: NCT03619213.
|
|
