Table 2.
Event rate (per 100 patient‐years) and risk of study endpoints according to duration of heart failure (HF 0–1 year as reference)
| HF 0–1 year | HF > 1–2 years | HF > 2–5 years | HF > 5 years | P‐Value | |
|---|---|---|---|---|---|
| No. of patients | 2523 | 1178 | 2054 | 2644 | |
| HF hospitalization or cardiovascular death, no. (%) | 442 (17.5) | 270 (22.9) | 569 (27.7) | 750 (28.4) | <0.001 |
| Event rates per 100 patient‐years (95% CI) | 8.4 (7.6–9.2) | 11.2 (10.0–12.7) | 13.4 (12.4–14.6) | 14.2 (13.2–15.2) | |
| Unadjusted HR | 1.00 (ref) | 1.35 (1.16–1.57) | 1.65 (1.46–1.87) | 1.76 (1.56–1.98) | |
| Adjusted a HR | 1.00 (ref) | 1.26 (1.07–1.48) | 1.52 (1.33–1.74) | 1.53 (1.33–1.75) | |
| Cardiovascular death, no. (%) | 295 (11.7) | 160 (13.6) | 346 (16.8) | 450 (17.0) | <0.001 |
| Event rates per 100 patient‐years (95% CI) | 5.3 (4.8–6.0) | 6.2 (5.3–7.2) | 7.5 (6.8–8.4) | 7.7 (7.0–8.5) | |
| Unadjusted HR | 1.00 (ref) | 1.18 (0.97–1.43) | 1.49 (1.27–1.74) | 1.63 (1.40–1.90) | |
| Adjusted a HR | 1.00 (ref) | 1.15 (0.93–1.42) | 1.40 (1.18–1.66) | 1.44 (1.22–1.71) | |
| HF hospitalization, no. (%) | 225 (8.9) | 158 (13.4) | 334 (16.3) | 478 (18.1) | <0.001 |
| Event rates per 100 patient‐years (95% CI) | 4.3 (3.7–4.9) | 6.6 (5.6–7.7) | 7.9 (7.1–8.8) | 9.0 (8.2–9.9) | |
| Unadjusted HR | 1.00 (ref) | 1.54 (1.26–1.89) | 1.86 (1.57–2.21) | 2.05 (1.74–2.42) | |
| Adjusted a HR | 1.00 (ref) | 1.33 (1.07–1.66) | 1.63 (1.36–1.96) | 1.66 (1.39–1.98) | |
| All‐cause mortality (no. of events), no. (%) | 362 (14.3) | 199 (16.9) | 432 (21.0) | 553 (20.9) | <0.001 |
| Event rates per 100 patient‐years (95% CI) | 6.6 (5.9–7.3) | 7.7 (6.7–8.8) | 9.4 (8.5–10.3) | 9.5 (8.7–10.3) | |
| Unadjusted HR | 1.00 (ref) | 1.18 (1.00–1.41) | 1.48 (1.29–1.70) | 1.56 (1.36–1.79) | |
| Adjusted a HR | 1.00 (ref) | 1.15 (0.96–1.39) | 1.37 (1.17–1.60) | 1.35 (1.16–1.58) | |
| Sudden death, no. (%) | 162 (6.4) | 77 (6.5) | 154 (7.5) | 168 (6.4) | 0.826 |
| ‐Event rates per 100 patient‐years (95% CI) | 2.9 (2.5–3.4) | 2.9 (2.3–3.6) | 3.3 (2.8–3.9) | 2.8 (2.4–3.3) | |
| Unadjusted HR | 1.00 (ref) | 1.05 (0.80–1.37) | 1.26 (1.01–1.57) | 1.19 (0.95–1.49) | |
| Adjusted a HR | 1.00 (ref) | 1.09 (0.81–1.46) | 1.23 (0.96–1.57) | 1.19 (0.93–1.53) | |
| Pump failure death, no. (%) | 54 (2.1) | 40 (3.4) | 78 (3.8) | 128 (4.8) | <0.001 |
| Event rates per 100 patient‐years (95% CI) | 1.0 (0.7–1.3) | 1.5 (1.1–2.1) | 1.7 (1.4–2.1) | 2.2 (1.8–2.6) | |
| Unadjusted HR | 1.00 (ref) | 1.56 (1.04–2.36) | 1.73 (1.22–2.45) | 2.32 (1.68–3.22) | |
| Adjusted a HR | 1.00 (ref) | 1.57 (1.01–2.46) | 1.67 (1.14–2.45) | 1.95 (1.35–2.83) | |
| Recurrent HF hospitalizations | |||||
| Total events | 339 | 255 | 536 | 800 | <0.001 |
| Event rates per 100 patient‐years (95% CI) | 6.1 (5.5–6.8) | 9.8 (8.7–11.1) | 11.6 (10.7–12.7) | 13.7 (12.8–14.7) | |
| Unadjusted RR b | 1.00 (ref) | 1.61 (1.37–1.90) | 1.92 (1.68–2.21) | 2.20 (1.93–2.51) | |
| Adjusted a RR | 1.00 (ref) | 1.36 (1.14–1.62) | 1.56 (1.34–1.80) | 1.66 (1.43–1.91) | |
| Significant worsening in KCCQ‐CSS (≥5) at 8 months, d no. (%) | 592 (23.7) | 346 (29.4) | 617 (30.3) | 852 (32.5) | <0.001 |
| Unadjusted OR | 1.00 (ref) | 1.35 (1.15–1.59) | 1.32 (1.16–1.52) | 1.46 (1.28–1.65) | |
| Adjusted c OR | 1.00 (ref) | 1.27 (1.08–1.50) | 1.22 (1.06–1.40) | 1.25 (1.09–1.44) | |
| Significant improvement in KCCQ‐CSS (≥5) at 8 months, d no. (%) | 689 (27.5) | 316 (26.9) | 572 (28.1) | 668 (25.5) | 0.20 |
| Unadjusted OR | 1.00 (ref) | 0.79 (0.66–0.93) | 0.76 (0.66–0.88) | 0.62 (0.54–0.70) | |
| Adjusted c OR | 1.00 (ref) | 0.84 (0.70–0.99) | 0.82 (0.71–0.95) | 0.70 (0.61–0.81) | |
| Change in KCCQ‐CSS at 8 months e (±SE) | −1.19 ± 0.44 | −4.31 ± 0.63 | −4.82 ± 0.46 | −5.10 ± 0.41 | <0.001 |
Model adjusted for age, sex, treatment arm, race, region, previous heart failure hospitalization, heart rate, systolic blood pressure, body mass index, New York Heart Association classification, left ventricular ejection fraction, baseline KCCQ clinical summary score, estimated glomerular filtration rate, history of myocardial infarction, history of atrial fibrillation, diabetes, and NT‐proBNP.
RR denotes rate ratios with 95% confidence intervals (CI) within parentheses, assessed using the LWYY model.
Model adjusted as for (a) except previous heart failure hospitalization.
Scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ) range from 0 to 100 (higher scores indicating fewer symptoms).
Change in mean KCCQ‐CSS at 8 months from baseline was assessed using a repeated‐measures mixed effects model with baseline KCCQ values, region, treatment arm, study visit, and the interaction between study visit and HF duration study group included in the model.