Initiation of Medical Therapy for Heart Failure Patients According to Kidney Function: A Danish Nationwide Study

Figures & data

Figure 1 Flowchart.

Abbreviations: HF, heart failure; eGFR, estimated glomerular filtration rate.

Table 1 Baseline Characteristics of the Study Population at Time of HF Diagnosis Stratified According to eGFR at Baseline

	eGFR ≥60	eGFR 30–59	eGFR <30	P-value
Individuals, No. (%)	25,438	13,723	3159
Age, No. (%)				<0.001
<65	8930 (35.1)	1241 (9.0)	327 (10.4)
65≤age<80	11,719 (46.1)	5758 (42.0)	1132 (35.8)
≥80	4789 (18.8)	6724 (49.0)	1700 (53.8)
Male sex, No. (%)	16,500 (64.9)	7904 (57.6)	1804 (57.1)	<0.001
Frailty score, median [IQR]	2.3 [0.0;6.0]	4.2 [1.4;9.0]	7.9 [3.8;13.7]	NA
Frailty risk group, No. (%)				<0.001
Low	17,731 (69.7)	7574 (55.2)	1033 (32.7)
Intermediate	6325 (24.9)	4713 (34.3)	1448 (45.8)
High	1382 (5.4)	1436 (10.5)	678 (21.5)
Plasma creatinine, mean (SD)	77 (16)	117 (23)	278 (180)	<0.001
Plasma potassium, median [IQR]*	4.0 [3.9;4.1]	4.0 [3.9;4.3]	4.0 [3.9;4.5]	NA
Outpatient primary diagnosis, No. (%)	16,496 (64.8)	7297 (53.2)	1399 (44.3)	<0.001
Pharmacotherapy, No. (%)
Beta-blocker	11,459 (45.0)	7522 (54.8)	1877 (59.4)	<0.001
Renin-angiotensin inhibitor	13,419 (52.8)	8101 (59.0)	1613 (51.1)	<0.001
Mineralocorticoid receptor antagonist	2790 (11.0)	2164 (15.8)	364 (11.5)	<0.001
Loop diuretics	8303 (32.6)	7652 (55.8)	2303 (72.9)	<0.001
Glucose-lowering drugs	4244 (16.7)	3057 (22.3)	974 (30.8)	<0.001
Thiazide diuretics	2628 (10.3)	1722 (12.5)	290 (9.2)	<0.001
Anticoagulants	7587 (29.8)	5937 (43.3)	1160 (36.7)	<0.001
Antiplatelets	9541 (37.5)	5442 (39.7)	1432 (45.3)	<0.001
Comorbidity, No. (%)
Ischemic heart disease	7828 (30.8)	4336 (31.6)	1189 (37.6)	<0.001
Peripheral arterial disease	1008 (4.0)	796 (5.8)	301 (9.5)	<0.001
Atrial fibrillation	6721 (26.4)	5411 (39.4)	1130 (35.8)	<0.001
Anemia**	6962 (27.4)	5782 (42.1)	2227 (70.5)	<0.001
Hyponatremia***	2081 (8.2)	1048 (7.6)	321 (10.2)	<0.001
Cancer	1985 (7.8)	1252 (9.1)	363 (11.5)	<0.001
Device	382 (1.5)	225 (1.6)	50 (1.6)	0.568

Notes: *Among 39,988 patients (94.5%) who had available data on potassium levels at inclusion. Not normal distributed. **According to WHO definition of anemia. Among 38,929 patients (92.0%) who had available data on haemoglobin levels at inclusion. ***Defined as plasma sodium below 135 mmol/l. Among 40,023 patients (94.6%) who had available data on sodium levels at inclusion.

Abbreviations: eGFR, estimated glomerular filtration rate; IQR, interquartile ranges; No., number; SD, standard deviation.

Figure 2 Six-month initiation rates of HF therapy treatment according to eGFR at baseline. (a) RAS inhibitor treatment. (b) MRA treatment. (c) BB treatment.

Table 2 Multivariate adjusted Hazard Ratios and 95 % Confidence Interval for HF therapy initiation

		HR (95% CI)*	P-value
RAS inhibitor	Kidney function at baseline
	eGFR ≥60	Reference
	eGFR 30-59	0.97 (0.93-1.02)	0.198
	eGFR <30	0.44 (0.40-0.49)	<0.0001
	Age
	<65	Reference
	65≤age<80	1.00 (0.96-1.05)	0.847
	≥80	0.72 (0.69-0.75)	<0.0001
	Frailty risk group
	Low	Reference
	Intermediate	0.72 (0.69-0.75)	<0.0001
	High	0.49 (0.45-0.53)	<0.0001
MRA	Kidney function at baseline
	eGFR ≥60	Reference
	eGFR 30-59	0.80 (0.77-0.83)	<0.0001
	eGFR <30	0.24 (0.21-0.27)	<0.0001
	Age
	<65	Reference
	65≤age<80	0.97 (0.93-1.01)	0.111
	≥80	0.68 (0.64-0.71)	<0.0001
	Frailty risk group
	Low	Reference
	Intermediate	0.84 (0.81-0.88)	<0.0001
	High	0.60 (0.56-0.66)	<0.0001
BB	Kidney function at baseline
	eGFR ≥60	Reference
	eGFR 30-59	1.09 (1.05-1.14)	<0.0001
	eGFR <30	1.06 (0.97-1.16)	0.186
	Age
	<65	Reference
	65≤age<80	0.91 (0.87-0.95)	<0.0001
	≥80	0.61 (0.58-0.65)	<0.0001
	Frailty risk group
	Low	Reference
	Intermediate	0.73 (0.70-0.76)	<0.0001
	High	0.51 (0.47-0.55)	<0.0001

Notes: *In addition, adjusted for concomitant pharmacotherapy, comorbidity, outpatient status and sex (estimates not shown).

Abbreviations: eGFR, estimated glomerular filtration rate; HR, hazard ratio; CI, confidence interval; RAS, renin-angiotensin receptor antagonists; MRA, mineralocorticoid receptor antagonist; BB, betablocker.

Figure 3 Cox proportional hazards models for HF therapy initiation according to eGFR at baseline. (a) RAS inhibitor treatment. (b) MRA treatment. (c) BB treatment.

Notes: Model 1: Unadjusted model. Model 2: Adjusted for sex, diagnostic setting, calendar year, concomitant comorbidity, plasma potassium, pharmacotherapy, and age. Model 3: Adjusted for sex, diagnostic setting, concomitant comorbidity, plasma potassium, pharmacotherapy, and frailty status. Model 4: Fully adjusted model, adjusted for sex, diagnostic setting, concomitant comorbidity, plasma potassium, pharmacotherapy, age, and frailty status.