This video discusses the role of Dapagliflozin in heart failure with reduced ejection fraction patients.
Hi my name is dr nitin in this series i shall be discussing some of the important clinical trials in cardiology today i am going to tell about the dappa hf trial that is dipagliflogin in patients with heart failure and reduced ejection fraction it was published by mcmurray at all in any jm in 2019 the study drug of this trial was dapagliflogic let’s know more
About dipagliflogin it inhibits sglt2 transporter proteins sglt2 transporter proteins are responsible for at least 90 percent of glucose reabsorption in the kidney hence blocking this transporter mechanism causes more blood glucose to be eliminated through the urine in clinical trials dipagliflogin lowered hp a1c by 0.6 vs placebo when it was added to metformin
It is used to improve glycemic control in patients with type 2 diabetes it also reduced the risk of hospitalization for heart failure among adults with type 2 diabetes and non-cardiovascular disease or other risk factors since dipagliflogin leads to heavy glycosyria it can lead to rapid weight loss and tiredness another side effect is that the glucose acts as an
Osmotic diuretic this effect is the cause of polyuria and diabetes and it can lead to dehydration thirdly the increased amount of glucose in the urine can also worsen the infections already associated with diabetes particularly urinary tract bacterial and fungal infections before this trial we already knew that in patients with type 2 diabetes inhibitors of sglt2
Transporter proteins reduce the risk of hospitalization for heart failure but more data are needed regarding the effects of sglt2 protein inhibitors in patients with established heart failure with a reduced ejection fraction regardless of the presence or absence of type 2 diabetes so the goal of this trial was to evaluate dipagliflogin which is a sglt2 inhibitor and
To compare it with placebo among patients with heart failure and reduced ejection fraction this was a phase 3 placebo control randomized trial more than 4500 patients with nyha class 2 3 or 4 heart failure and digestion fraction of 40 percent or less were included they received either dipagliflozin or placebo in addition to the recommended heart failure therapy
The dose of dipagliflogin was 10 milligram per day the primary outcome was a composite of worsening heart failure event leading to hospitalization or cardiovascular death the patients included in this trial had symptomatic heart failure left ventricular ejection fraction less than equal to 40 percent anti-probe vnp value of more than equal to 600 picogram per ml
However if the patient was hospitalized for heart failure within last 12 months then the cut-off value of anti-problem p was taken as more than equal to 400 picogram per ml and if atl fibrillation or clutter was present then the cutoff was more than 900 picogram per ml for the inclusion exclusion criteria were estimated gfr less than 30 symptomatic hypotension
Or systolic blood vessels less than 95 the other important point of this trial was that the patients with type 1 diabetes were not included hence the results should not be extended to those patients in short it was a randomized placebo-controlled trial patients with heart failure with reduced ejection fraction irrespective of diabetes status were randomized to
Dipagliflogin 10 milligram per day versus placebo the duration of follow-up was approximately 18 months other baseline characteristics were that means of the recruited patients were 66 years females were 24 percent and diabetics were 42 in this trial coming to the results now depaglogen reduced the primary outcomes significantly compared to placebo the primary
Outcome of cardiovascular death hospitalization for heart failure or urgent heart failure visit occurred in 16.3 percent of depagliflozin group compared with 21.2 percent of the placebo group the hazard ratio was 0.74 and the p value was less than 0.001 the benefit was similar in all pre-specified subgroups including according to the diabetes status talking
About the secondary outcomes the cardiovascular deaths and all-cause deaths were lesser with dipagliflogen worsening of the renal function was similar between dipagliflogin and placebo again the secondary outcomes in patients with diabetes was similar to those in patients without diabetes and most importantly the frequency of adverse events related to volume
Depletion renal dysfunction and hypoglycemia did not differ between treatment groups talking about some of the pre-specified subgroups when results were stratified according to the age groups the benefits were consistent in all the is strata the hazard ratio was less than one in all four ace categories as i told earlier the primary outcomes were decreased by
Same magnitude in both diabetics and non-diabetics we can see that hazard ratio is less than 1 in both groups the benefits were more pronounced when patients were already receiving optimal doses of ace inhibitors arvs beta blockers or mineralocorticoid receptor antagonists depagliplosion reduced both first time event as well as recurrent events with same degree of
Magnitude concluding the findings among patients with heart failure and reduced ejection fraction the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dipagliflogen than among those who received placebo and it was regardless of the presence or absence of diabetes hence depa-hf trials showed that dipacliplogin
Was superior to placebo at preventing cardiovascular deaths in heart failure events the benefit was consistent across the age spectrum in diabetics non-diabetics across the range of baseline health status and baseline medication use there was no sign of adverse safety events so finally depaglophylogen may signal a new approach in the treatment of patients with
Heart failure and reduced ejection fraction thank you for watching this video if you want to know more about such clinical trials do subscribe to this channel
Transcribed from video
DAPA-HF clinical trial I Dapagliflozin I HFrEF By Learning Cardiology
