Sodium-glucose cotransporter 2 inhibitors have demonstrated constructive results in coronary heart failure (HF) sufferers. Nevertheless, the results of dapagliflozin in sufferers with decompensated HF stay unclear. This research aimed to match the efficacy and security of early and late dapagliflozin administration for decompensated HF. Information concerning dapagliflozin administration from 70 sufferers identified with HF between December 2020 and November 2021 at a Japanese coronary heart centre had been analysed retrospectively. Propensity rating matching was carried out to match the medical outcomes of early and late dapagliflozin administration for decompensated HF. The first finish level was HF admission one 12 months after dapagliflozin administration. The secondary finish factors had been evaluated based mostly on 24-hour urine quantity, cardiac loss of life, adjustments in ejection fraction (EF), blood stress, glomerular filtration fee (GFR), haemoglobin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) ranges, and unintended effects inside one 12 months of remedy. Fifteen matched pairs of sufferers had been analysed. Admission fee inside one 12 months was considerably decrease within the early administration group than within the late administration group (0 vs. 20%, p=0.03). Secondary finish factors weren’t considerably totally different between the 2 teams. In conclusion, early dapagliflozin administration considerably decreased HF admission inside one 12 months of remedy, though no variations had been noticed in 24-hour urine quantity, cardiac loss of life, EF, GFR, haemoglobin and NT-proBNP ranges, and unintended effects.
Introduction
Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, was first used as a kind 2 diabetes drug. Nevertheless, within the Dapagliflozin and Prevention of Opposed Outcomes in Coronary heart Failure (DAPA-HF) trial, dapagliflozin successfully decreased each hospitalisations as a result of coronary heart failure (HF) and loss of life in sufferers with HF with decreased ejection fraction (HFrEF).1 Due to this fact, the European Society of Cardiology (ESC) and Japanese Circulation Society (JCS) pointers really helpful the administration of SGLT2 inhibitors to sufferers with HFrEF.2,3 Furthermore, dapagliflozin suppressed each renal failure exacerbation and all-cause loss of life in sufferers with continual renal failure.4 A current research revealed that dapagliflozin administration decreased HF hospitalisation in sufferers with HF with preserved ejection fraction (HFpEF).5 In these research, dapagliflozin was administered to sufferers with continual HF; nonetheless, none have reported the security or efficacy of its administration within the acute part. A current research reported that the administration of SGLT2 inhibitors in sufferers with HF decreased using diuretics and elevated urine output.4 SGLT2 inhibitors are used for sufferers with chronic-phase HF; nonetheless, contemplating their diuretic impact, they could be administered to sufferers with decompensated HF. A current research reported that empagliflozin administration may benefit sufferers with decompensated HF.5 Nevertheless, no research have examined the results of dapagliflozin administration in sufferers with decompensated HF. Due to this fact, this research aimed to analyze the security and efficacy of dapagliflozin administration in sufferers with decompensated HF.
Supplies and technique
Research design and sufferers
The information of hospitalised sufferers who had been administered dapagliflozin remedy for decompensated HF at Nagoya Coronary heart Middle between December 2020 and November 2021 had been retrospectively analysed. Seventy consecutive sufferers with decompensated HF had been included within the evaluation. All sufferers obtained 10 mg dapagliflozin. A 1:1 propensity rating matching (PSM) of populations divided into early and late dapagliflozin administration teams was carried out.
Comply with-up medical evaluations had been carried out at one, six, and 12 months utilizing medical signs, cardiac loss of life, important indicators, laboratory information, ejection fraction (EF), HF admission, and unintended effects. Comply with-up information had been obtained from hospital charts or by contacting the sufferers, relations, or referring physicians. The research protocol was authorised by the ethics committee of Nagoya Coronary heart Middle and was performed in accordance with the tenets of the Declaration of Helsinki. Owing to the retrospective enrolment, the requirement for acquiring written knowledgeable consent from the sufferers was waived.
Finish factors
The first finish level was HF admission one 12 months after dapagliflozin administration. The secondary finish factors had been evaluated based mostly on 24-hour urine quantity, cardiac loss of life, the adjustments in EF, glomerular filtration fee (GFR), haemoglobin degree, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) degree inside one 12 months after remedy. The secondary finish factors included drug unintended effects, together with hypoglycaemia, fracture, amputation, dehydration, urinary tract an infection, allergy, and diabetic ketoacidosis (DKA), inside one 12 months of remedy.
Definitions
HF was outlined as a medical syndrome consisting of cardinal signs (corresponding to breathlessness, ankle swelling, and fatigue) which may be accompanied by indicators (corresponding to elevated jugular venous stress, pulmonary crackles, and peripheral oedema), as a result of a structural and/or useful abnormality of the center that induces elevated intracardiac stress and/or insufficient cardiac output at relaxation and/or throughout train.6,7 HFrEF was outlined as an ejection fraction of <40%.6 Early dapagliflozin administration was outlined as administration inside one week of HF prognosis. The classification of continual kidney illness (CKD) was outlined in response to the Kidney Illness Bettering International Outcomes CKD classification system.8
Statistical evaluation
All statistical analyses had been carried out utilizing the JMP model 14.0.2 software program (SAS Institute Inc., Cary, NC, USA). To get rid of the potential affect of the non-randomised research design, PSM was carried out utilizing a multi-variate logistic-regression mannequin with the dapagliflozin administration technique (early vs. late administration of dapagliflozin) because the dependent variable. All baseline traits (age, intercourse, physique mass index, hypertension, diabetes mellitus, dyslipidaemia, CKD, atrial fibrillation, ischaemic coronary heart failure, present smoking standing, de novo, New York Coronary heart Affiliation [NYHA] classification, EF, angiotensin-converting enzyme [ACE] inhibitor/angiotensin-receptor blocker [ARB]/angiotensin-receptor/neprilysin inhibitor [ARNI], beta blocker, mineralocorticoid-receptor antagonist [MRA], loop diuretic, tolvaptan, baseline blood stress, estimated glomerular filtration fee [eGFR], haemoglobin degree, and NT-proBNP degree) had been set as covariates. Based on the advice by Austin, a caliper cutoff of 0.20 was used to acquire a passable stability.9 Information are offered as numbers, percentages, means ± commonplace deviations (SD), or medians (interquartile ranges, IQR). Categorical variables had been in contrast between the teams utilizing the χ2 or Fisher’s precise take a look at, as acceptable. Steady variables had been in contrast between the teams utilizing the Mann–Whitney U take a look at. A likelihood (p) worth of <0.05 was thought of statistically vital.
Outcomes
Sufferers
A flowchart of the research is proven in determine 1. Of the 70 sufferers included for evaluation, 15 and 55 obtained early and late dapagliflozin administration, respectively. The entire baseline medical information and affected person traits are proven in desk 1. After PSM, 15 matched pairs of sufferers had been included for evaluation. Within the matched populations, no vital variations had been noticed in baseline traits and medical information between the 2 teams. The imply age of the sufferers was 73 years, 53% had been male, 27% had ischaemic coronary heart failure, imply left ventricular EF was 45%, and median NT-proBNP degree was 4,481 pg/ml. The typical size of dapagliflozin administration was 1.7 ± 0.8 versus 33.5 ± 17.8 days within the early and late teams (p<0.01).
Desk 1. Baseline traits and medical information of the research inhabitants earlier than and after propensity rating matching
Character
Earlier than matching
After matching
Early group
Late group
p worth
Early group
Late group
p worth
Quantity
15
55
15
15
Imply age ± SD, years
74.4 ± 11.6
71.0 ± 11.9
0.42
74.4 ± 11.6
71.1 ± 13.2
0.46
Male, n (%)
42 (76.4)
8 (53.3)
0.09
8 (53.3)
8 (53.3)
1.0
Imply BMI ± SD, kg/m2
23.2 ± 3.8
24.9 ± 4.8
0.19
23.2 ± 3.8
24.1 ± 4.8
0.58
Hypertension, n (%)
13 (86.7)
50 (90.9)
0.64
13 (86.7)
14 (93.3)
0.54
Diabetes mellitus, n (%)
8 (53.3)
46 (83.6)
0.02
8 (53.3)
12 (80.0)
0.12
Dyslipidaemia, n (%)
10 (66.7)
46 (83.6)
0.16
10 (66.7)
14 (93.3)
0.07
Atrial fibrillation, n (%)
6 (40.0)
8 (14.6)
0.04
6 (40.0)
2 (20.0)
0.22
Ischaemic coronary heart failure, n (%)
2 (13.3)
22 (40.0)
0.04
2 (13.3)
6 (40.0)
0.09
Present smoking, n (%)
5 (33.3)
25 (45.5)
0.40
5 (33.3)
5 (33.3)
1.0
Imply ejection fraction ± SD, %
42.5 ± 20.2
43.9 ± 16.7
0.79
42.5 ± 20.2
47.3 ± 19.2
0.53
HFrEF, n (%)
9 (60.0)
23 (41.8)
0.21
9 (60.0)
7 (46.7)
0.46
Imply baseline eGFR ± SD, ml/min/1.73 m2
52.5 ± 23.9
56.9 ± 23.0
0.52
52.5 ± 23.9
57.8 ± 19.5
0.51
Imply haemoglobin ± SD, g/dL
13.2 ± 2.6
13.2 ± 2.5
0.90
13.2 ± 2.6
13.7 ± 2.7
0.60
Imply NT-proBNP ± SD, pg/ml
5,172 ± 2,320
4,014 ± 1,964
0.48
5,172 ± 2,320
3,790 ± 1,710
0.29
Persistent kidney illness, n (%)
Stage 3a
1 (6.7)
7 (12.7)
0.50
1 (6.7)
1 (6.7)
0.83
Stage 3b
2 (13.3)
11 (20.0)
2 (13.3)
1 (6.7)
Stage 4
3 (20.0)
6 (10.9)
3 (20.0)
1 (6.7)
NYHA classification, n (%)
II
6 (40.0)
28 (50.9)
0.27
6 (40.0)
8 (53.3)
0.20
III
6 (40.0)
25 (45.5)
6 (40.0)
7 (46.7)
IV
3 (20.0)
2 (3.6)
3 (20.0)
0 (0)
Remedy, n (%)
ACEi/ARB/ARNI
10 (66.7)
37 (67.3)
0.96
10 (66.7)
11 (73.3)
0.69
Beta blocker
13 (86.7)
42 (76.4)
0.37
13 (86.7)
10 (66.7)
0.19
MRA
5 (33.3)
21 (38.2)
0.73
5 (33.3)
3 (20.0)
0.41
Loop diuretic
9 (41.8)
23 (41.8)
0.21
9 (60.0)
4 (26.7)
Tolvaptan
1 (6.7)
9 (16.4)
0.31
1 (6.7)
1 (6.7)
1.0
Imply blood stress ± SD, mmHg
Systolic
129.5 ± 23.2
125.7 ± 19.3
0.43
129.5 ± 23.2
127.4 ± 18.0
0.78
Diastolic
78.6 ± 19.1
71.2 ± 10.7
0.06
78.6 ± 19.1
70.8 ± 18.3
0.16
Key: ACE = angiotensin-converting enzyme inhibitor; ARB = angiotensin-receptor blocker; ARNI = angiotensin-receptor/neprilysin inhibitor; BMI = physique mass index; eGFR = estimated glomerular filtration fee; HFrEF = coronary heart failure with decreased ejection fraction; MRA = mineralocorticoid-receptor antagonist; NT-proBNP = N-terminal pro-B-type natriuretic peptide; NYHA = New York Coronary heart Affiliation; SD = commonplace deviation
Major and secondary outcomes
The first and secondary outcomes are proven in desk 2. The HF admission fee was considerably decrease with early dapagliflozin administration than with late dapagliflozin administration (0 vs. 20%, p<0.03). Nevertheless, no vital variations had been noticed concerning 24-hour urine quantity, cardiac loss of life, the adjustments in EF, GFR, haemoglobin degree, and NT-proBNP degree inside one 12 months between the 2 teams. The incidence of unintended effects was related for sufferers in each teams, and just one occasion of dehydration was noticed within the late-administration group.
Desk 2. Major and secondary medical outcomes
Early groupN=15
Late groupN=15
p worth
Acute part
Imply admission days ± SD
14.4 ± 8.9
22.7 ± 9.8
0.35
Imply bed-rest days ± SD
2.0 ± 1.8
5.7 ± 6.3
0.18
Imply BUN/Cr at discharge ± SD
17.6 ± 4.4
21.6 ± 6.3
0.06
Persistent part
HF admission inside 1 12 months, n (%)
0 (0)
3 (20.0)
0.03
Imply loop diuretic dose ± SD, mg
18.0 ± 6.3
21.7 ± 9.8
0.38
Imply ejection fraction ± SD, %
53.8 ± 10.7
54.2 ± 17.0
0.95
Imply eGFR ± SD, ml/min/1.73 m2
56.4 ± 19.7
59.1 ± 18.2
0.74
Imply haemoglobin ± SD, g/dL
13.6 ± 1.5
14.6 ± 1.8
0.15
Imply NT-proBNP ± SD, pg/ml
1,325 ± 2,142
1,046 ± 1,772
0.75
Hypoglycaemia, n (%)
0 (0)
0 (0)
–
Fracture, n (%)
0 (0)
0 (0)
–
Amputation, n (%)
0 (0)
0 (0)
–
Dehydration, n (%)
0 (0)
1 (6.7)
0.23
Urinary tract an infection, n (%)
0 (0)
0 (0)
–
Allergy, n (%)
0 (0)
0 (0)
–
DKA, n (%)
0 (0)
0 (0)
–
Key: BUN = blood urea nitrogen; Cr = creatinine; DKA = diabetic ketoacidosis; eGFR = estimated glomerular filtration fee; HF = coronary heart failure; NT-proBNP = N-terminal pro-B-type natriuretic peptide; SD = commonplace deviation
Dialogue
This research demonstrated that early dapagliflozin administration considerably decreased HF admission inside one 12 months of remedy in contrast with late dapagliflozin administration. Nevertheless, no distinction in unintended effects was noticed between the 2 teams.
As sufferers weren’t randomised into the 2 teams, doable variations in baseline medical traits could ensue; subsequently, PSM was carried out; nonetheless, no vital variations had been noticed within the medical traits between the 2 teams after PSM. From a primary medical standpoint, dapagliflozin has been demonstrated to scale back sympathetic nerve excitation and to have diuretic and renal protecting results.10,11 Due to this fact, it was hypothesised that dapagliflozin is likely to be used for each sufferers with continual coronary heart failure and people with decompensated HF. Empagliflozin administration to sufferers with decompensated HF has improved congestion in each the quick and medium phrases.12 Furthermore, it has been reported that early and full congestion aid improves prognosis.13,14 Due to this fact, it was hypothesised that early dapagliflozin administration to enhance congestion at an early stage would enhance prognosis by decreasing the variety of HF hospitalisations. Our research outcomes revealed that HF hospitalisation was suppressed after dapagliflozin administration within the early dapagliflozin administration group; this can be attributed to the doable affiliation of early dapagliflozin administration with an entire discount in congestion.
A current research demonstrated that the results of dapagliflozin differ over time, suggesting that its early administration could additional scale back cardiovascular mortality and hospitalisation. Based on this research, the useful results of dapagliflozin manifest within the early part of administration.15 One other research demonstrated that natriuresis and intracardiac filling pressures are favourably modified inside days of remedy initiation;16 this mechanism would possibly confer medical advantages in circumstances of early dapagliflozin administration in sufferers with HF. Nevertheless, this research was restricted to sufferers with HF with mildly decreased or preserved ejection fraction, and our research centered on all sufferers with HF. A earlier research reported that dapagliflozin administration might scale back HF hospitalisations even when stratified by EF, in step with this research.17 As well as, our research demonstrated that early dapagliflozin administration didn’t enhance unintended effects. Though our research had a restricted variety of circumstances, dapagliflozin could also be safely used, even when administered early after congestion prognosis. The research findings and long-term medical outcomes require additional validation in potential research.
Our research had a number of limitations. First, the variety of sufferers with decompensated HF was small. Second, the research design was retrospective, inciting doable choice bias. Due to this fact, PSM was carried out to beat baseline variations. Third, the research centered solely on Japanese sufferers with decompensated HF; thus, the outcomes is probably not relevant to different populations. Lastly, the research cohort was restricted to dapagliflozin administration; thus, whether or not the outcomes are relevant to different SGLT2 inhibitors, corresponding to empagliflozin, stays unknown. Due to this fact, additional potential research are required to verify the research outcomes.
Total, on this research, early dapagliflozin administration considerably decreased HF admission inside one 12 months of remedy, though no variations had been noticed within the EF, GFR, haemoglobin degree, NT-proBNP degree, and unintended effects.
Key messages
In contrast with late administration, early dapagliflozin administration considerably decreased coronary heart failure-related admission inside one 12 months of remedy
Early administration of dapagliflozin didn’t enhance unintended effects inside one 12 months of remedy
No vital variations had been noticed between early and late dapagliflozin administration in glomerular filtration fee, ejection fraction, haemoglobin degree, and NT-proBNP degree inside one 12 months of remedy
Conflicts of curiosity
None declared.
Funding
None.
Research approval
The research protocol was authorised by the ethics committee of Nagoya Coronary heart Middle and was performed in accordance with the tenets of the Declaration of Helsinki.
Acknowledgement
The authors thank the employees within the catheterisation laboratory of Nagoya Coronary heart Middle for his or her help with this work.
References
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