Table 2.
Events, event rates, and hazard ratios for the screening and time‐updated potassium categories for key study outcomes in the PARAGON‐HF trial
| K+ (mmol/L) | Events, n (%) | Incidence rate per 100 py | Screening model (crude) | Screening model (adjusted) | P‐value * | Time‐updated model (crude) | Time‐updated model (adjusted) | P‐value * | K+ by eGFR interaction P‐value ** |
|---|---|---|---|---|---|---|---|---|---|
| Primary outcome | |||||||||
| <4 | 276 (33.8) | 16.0 (13.0–20.0) | 1.06 (0.84–1.33) | 1.03 (0.83–1.30) | 0.77 | 1.55 (1.30–1.85) | 1.55 (1.30–1.85) | <0.001 | |
| 4–5 | 1466 (29.3) | 13.1 (12.1–14.2) | Referent | Referent | – | Referent | Referent | – | 0.46 |
| >5 | 161 (35.4) | 17.2 (13.3–22.7) | 1.42 (1.08–1.87) | 1.29 (0.99–1.69) | 0.058 | 1.60 (1.35–1.88) | 1.21 (1.02–1.44) | 0.025 | |
| Total HF hospitalisations | |||||||||
| <4 | 225 (27.5) | 13.1 (10.3–16.8) | 1.09 (0.84–1.40) | 1.03 (0.81–1.32) | 0.79 | 1.64 (1.24–2.00) | 1.61 (1.33–1.96) | <0.001 | |
| 4–5 | 1134 (22.6) | 10.1 (9.2–11.1) | Referent | Referent | – | Referent | Referent | – | 0.67 |
| >5 | 128 (28.1) | 13.7 (10.2–18.8) | 1.48 (1.08–2.03) | 1.34 (0.99–1.81) | 0.060 | 1.64 (1.36–1.97) | 1.26 (1.04–1.52) | 0.019 | |
| CV death | |||||||||
| <4 | 51 (8.6) | 3.0 (2.2–3.9) | 1.00 (0.74–1.34) | 1.01 (0.75–1.37) | 0.93 | 1.37 (1.03–1.81) | 1.42 (1.06–1.89) | 0.018 | |
| 4–5 | 332 (8.6) | 3.0 (2.7–3.3) | Referent | Referent | – | Referent | Referent | – | 0.004 |
| >5 | 33 (10.1) | 3.5 (2.5–5.0) | 1.19 (0.83–1.70) | 1.13 (0.79–1.62) | 0.51 | 1.56 (1.20–2.03) | 1.16 (0.88–1.52) | 0.29 | |
| All‐cause death | |||||||||
| <4 | 82 (13.9) | 4.8 (3.8–5.9) | 0.96 (0.76–1.21) | 0.99 (0.78–1.25) | 0.90 | 1.46 (1.17–1.80) | 1.51 (1.21–1.87) | <0.001 | |
| 4–5 | 554 (14.3) | 4.9 (4.6–5.4) | Referent | Referent | – | Referent | Referent | – | 0.042 |
| >5 | 55 (16.8) | 5.9 (4.5–7.6) | 1.19 (0.90–1.57) | 1.12 (0.85–1.48) | 0.43 | 1.39 (1.13–1.72) | 1.06 (0.85–1.32) | 0.61 | |
| Non‐CV death | |||||||||
| <4 | 29 (4.9) | 1.7 (1.2–2.4) | 1.07 (0.72–1.59) | 1.09 (0.73–1.62) | 0.69 | 1.69 (1.18–2.42) | 1.72 (1.20–2.48) | 0.003 | |
| 4–5 | 175 (4.5) | 1.6 (1.3–1.8) | Referent | Referent | – | Referent | Referent | – | 0.28 |
| >5 | 16 (4.9) | 1.7 (1.0–2.8) | 1.10 (0.66–1.84) | 1.03 (0.61–1.72) | 0.92 | 1.13 (0.75–1.69) | 0.93 (0.61–1.40) | 0.71 |
CV, cardiovascular; eGFR, estimated glomerular filtration rate (mL/min/1.73 m2); HF, heart failure; K+, serum potassium (mmol/L); py, patient‐years.
Notes: The interaction P of K+ by eGFR (<60 or ≥60 mL/min/1.73 m2) and treatment (sacubitril/valsartan or valsartan) was assessed in the fully adjusted model. The P for interaction with eGFR is presented in the table. The P for interaction with treatment was non‐significant for all comparisons, as follows: primary outcome =0.96; total HF hospitalisations =0.96; CV death =0.25; all‐cause death =0.13; non‐CV death =0.31.
All models are adjusted for age, sex, race, region, systolic blood pressure, heart rate, body mass index, eGFR (categorical: <60 vs. ≥60 mL/min/1.73 m2), blood urea nitrogen, ischaemic cardiomyopathy, left ventricular ejection fraction, N‐terminal pro‐B‐type natriuretic peptide, New York Heart Association class, hypertension, diabetes, atrial fibrillation, prior HF hospitalisation, prior stroke, use of diuretics, beta‐blockers, mineralocorticoid receptor antagonists, and treatment group allocation (sacubitril/valsartan or valsartan).
P‐value for the fully adjusted model.
Interaction P‐value for the fully adjusted time‐updated model. Significant interactions are presented in Table 3 , separated by eGFR subgroups.