Dr Alice M Jackson (University of Glasgow, Glasgow, UK) discusses the findings from a DAPA-HF sub-analysis. The analysis focused on dapaglifozin and its diuretic use in patients with heart failure and reduced ejection fraction (HFrEF).
My name is dr. alice jackson i’m a clinical research fellow at the university of glasgow in scotland and i have been discussing today an analysis of diuretic youths in the daf hf trial which we presented recently at the h the esc hf a discovery session the tap hf trial was a randomized control trial of the sodium-glucose cotransport or 2 inhibitor ectopic illusion
Versus placebo in patients with heart failure and reduced ejection fraction both with and without diabetes four thousand seven hundred and forty four patients were randomized and these were patients with new york heart association class two three or four heart failure a left ventricular ejection fraction of 40 percent relax and an elevated natural etic peptide
Level the primary outcome of the trial was a composite of a worsening heart failure event or death from cardiovascular causes and after a median follow-up with about 18 months there was a 26 percent reduction in the risk of the primary outcome with topical flows and compared with placebo with event rates for all three components of the primary outcome favoring
Dapa callosum topic illusion was well tolerated and safety outcomes were similar between the randomized groups and importantly the benefit of topical flows and was consistent in patients with and without diabetes we know the inhibition of sglt2 and the proximal convoluted renal tubules leads to natural recess increased urinary glucose and consequently water
Loss we also know that 84% of patients in the dap hf trial were taking a conventional diuretic at baseline however not much is known about the effects of adding and sglt2 inhibitors to conventional diuretics and patients with harris so we felt that understanding the interaction between these groups of drugs would be of fundamental importance to the use of depo
Collusion in patients with heffron so with that in mind we examined the efficacy and safety of deepika frozen according to baseline diuretic therapy and also across baseline diuretic doses and we then also examined changes in diuretic requirements and other markers of interest over time such as hematocrit systolic blood pressure and creatinine with respect to
Daf hf it was a randomized control trial of deepika losing ten milligrams once daily versus placebo in patients with heifer f and patients were randomized on the basis of a diagnosis of the type 2 diabetes or no type 2 diabetes so stratified on the basis of their diabetic status and in this analysis we stratified patients according to whether they were taking
A conventional diuretic at baseline or not and then across the diuretic dose groups so we calculated a freeze amide equivalent loop diuretic dose in all patients we excluded 128 patients in whom the loop diuretic dose at baseline was indeterminate so the final cohort we analyzed and this study was comprised four thousand six hundred and sixteen patients and
We categorized patients into four groups according to their baseline dose so one those are no diuretic to those on less than 40 milligrams freeze might equivalent diuretic three those on exactly 40 milligrams freeze might equivalent diuretic and for those on greater than 40 milligrams freeze might equivalent diuretic and patients on a non loop diuretic only
So most commonly a thigh high diuretic were included in the low dose group the greece the group of less than 40 milligrams we found notable differences in patient characteristics across the diuretic categories compared to patients on no diuretics those on the highest diuretic doses were younger at higher natriuretic peptide levels worse symptoms a lower left
Ventricular ejection fraction worse renal function and more often had had a prior heart failure hospitalization atrial fibrillation or diabetes we found that the mean dose of loop diuretic in the trial was 60 milligrams overall and was similar in both randomized groups and although a reduction in dose was more common with dap collusion than with placebo the
Majority of patients in the trial did not change their diuretic dose during follow-up we also found that the benefit of deepika flows and persisted irrespective of diuretic use or dose we found that combining at typical flows and with conventional diuretics was safe there was slightly more volume depletion in patients taking dapa glyph luzon and diuretics but
Importantly this did not lead to increased frequency of drug discontinuation or of renal adverse events and finally we found a sustained elevation in hematocrit with typical flows and across all diuretic those categories and this persisted even despite a reduction in diuretic dose at 6 and 12 months well we still don’t fully understand how sglt2 inhibitors
Exert their benefits in patients with heart failure and reduced ejection fraction one suggestion is their diuretic effect in this study we found that combining depo collusion with conventional diuretics did not have a major impact on the use of diuretics in the majority of patients and nor was there a clear diuretic dose effect with respect to the benefits of
Depo callosum these findings don’t preclude a diuretic effect or a potential benefit related to that but there are certainly some signals from this study of other potential mechanisms of action that may be contributing and in particular our findings to suggest that factors other than hemo concentration might account for the elevation and hematocrit seen with
Dhokla frozen and there is some evidence from other studies showing the treatment with sglt2 inhibitors results in an increase in erythropoietin levels but certainly more researchers is needed in this area the main take-home message from from this study is that we found most patients do not change their diuretic dose after starting dapa the frozen and that the
Drug remains safe and effective irrespective of diuretic use or of diuretic dose and this is important clinically when looking after patients with heart failure and reduced ejection fraction who may be on both an sglt2 inhibitors and a conventional diuretic
Transcribed from video
HFA 2020: Dapagliflozin and diuretic use in patients with HFrEF in DAPA-HF — Dr Alice M Jackson By Radcliffe