Effect of dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia

Table 1 Baseline characteristics of participants, n (%)/ mean ± SD

Variable	Age (yr)	Sex (male)	LVEF (%)	NYHA class	Comorbidities	Medications	Serum uric acid (mg/dL)	eGFR (mL/min/1.73 m2)
Dapagliflozin group (n = 100)	62.3 ± 9.8	68	32.5 ± 6.7	II: 36; III: 52; IV: 12	Diabetes: 42; hypertension: 76; coronary artery disease: 54; renal impairment: 28	ACEI/ARB: 92; β-blocker: 88; MRA: 72; Diuretic: 80	7.5 ± 1.2	60.4 ± 15.8
Placebo group (n = 100)	63.1 ± 10.2	66	33.2 ± 7.1	II: 38; III: 50; IV: 12	Diabetes: 40; hypertension: 78; coronary artery disease: 56; renal impairment: 30	ACEI/ARB: 90; β-blocker: 86; MRA: 70; diuretic: 82	7.6 ± 1.3	59.8 ± 16.2
P value	0.56	0.81	0.47	0.73	0.83; 0.77; 0.81; 0.79	0.67; 0.73; 0.79; 0.77	0.62	0.74

LVEF: Left ventricular ejection fraction; NYHA: New York heart association; eGFR: Estimated glomerular filtration rate; ACEI: Angiotensin-converting enzyme inhibitor; ARB: Angiotensin receptor blocker; MRA: Mineralocorticoid receptor antagonist.

Table 2 Primary outcomes of changes in serum uric acid levels over time

Serum uric acid (mg/dL)	0 month	6th month	12th month	18th month	24th month
Dapagliflozin group	7.5 ± 1.2	6.8 ± 1.1	6.5 ± 1.0	6.4 ± 1.0	6.3 ± 1.1
Placebo group	7.6 ± 1.3	7.5 ± 1.2	7.6 ± 1.3	7.5 ± 1.2	7.5 ± 1.2

Table 3 Secondary outcomes, n (%)/mean ± SD/ median (25^th-75^th percentiles)

Outcome	Serum uric acid (mg/dL)	LVEF	NT-proBNP (pg/mL)	QoL score	Cardiovascular death or hospitalization for heart failure
Dapagliflozin group (n = 100)	Baseline: 7.5 ± 1.2; 24 months: 6.3 ± 1.1; Change: -1.2 ± 0.8	Baseline: 32.5 ± 6.7; 24 months: 36.0 ± 6.5; Change: 3.5 ± 2.4	Baseline: 1200 (800-1800); 24 months: 900 (600-1400); Change: -25% (-35% to -15%)	Baseline: 60 (50-70); 24 months: 70 (60-80); Change: 10 (5-15)	18
Placebo group (n = 100)	Baseline: 7.6 ± 1.3; 24 months: 7.5 ± 1.2; Change: -0.1 ± 0.7	Baseline: 33.2 ± 7.1; 24 months: 32.7 ± 7.0; Change: -0.5 ± 2.3	Baseline: 1250 (850-1900); 24 months: 1300 (900-2000); Change: 5% (-10%-20%)	Baseline: 58 (48-68); 24 months: 58 (48-68); Change: 0 (-5-5)	28
P value	< 0.001	< 0.001	< 0.001	< 0.001	0.002; Hazard ratio 95%CI: 0.65 (0.50-0.85)

LVEF: Left ventricular ejection fraction; NT-proBNP: N-terminal pro-B-type natriuretic peptide; QoL: Quality of life.

Table 4 Subgroup analysis of serum uric acid level changes

Subgroups	Dapagliflozin group	Placebo group
Age	-1.3 ± 0.7	-0.2 ± 0.6
Sex	-1.2 ± 0.8	-0.1 ± 0.7
Diabetes status	-1.1 ± 0.8	-0.2 ± 0.7
Baseline serum uric acid level	-1.2 ± 0.8	-0.1 ± 0.7
Baseline eGFR	-1.1 ± 0.8	-0.1 ± 0.7

eGFR: Estimated glomerular filtration rate.

Table 5 Adverse events and safety outcomes

Event	Dapagliflozin group (n = 100)	Placebo group (n = 100)	P value
Adverse events	64	62	0.83
Common adverse events
Infection	28	26	0.79
Hypotension	16	14	0.77
Renal impairment	12	10	0.73
Genital infection	10	2	0.01
Serious adverse events	20	22	0.79
Death	8	10	0.67