Introduction
Methods
Patient Population
Biochemical Analyses
Statistical Analysis
Subpopulation Treatment Effect Pattern Plot
Sum Score Model
Internal Validation
Results
Variable | Rolofylline | Placebo |
p value |
---|---|---|---|
Number | 1313 | 650 | |
Demographics | |||
Sex (% male) | 66.9 (878) | 66.6 (433) | 0.951 |
Age (years) | 70.1 ± 11.7 | 70.2 ± 11.5 | 0.852 |
BMI (kg/m2) | 28.9 ± 6.1 | 28.7 ± 6.2 | 0.612 |
LVEF (%) | 32.1 ± 12.7 | 32.4 ± 13.6 | 0.709 |
HFPEF (%) | 18.6 (118) | 21 (65) | 0.447 |
Systolic blood pressure (mmHg) | 124.4 ± 17.5 | 124.3 ± 17.8 | 0.911 |
Diastolic blood pressure (mmHg) | 73.7 ± 11.8 | 74.1 ± 11.9 | 0.472 |
Heart rate (beats/min) | 80 ± 15.3 | 80.6 ± 15.7 | 0.408 |
Clinical profile | |||
Atrial fibrillation on presentation | 38.1 (203) | 47.7 (124) | 0.012 |
Orthopnea (%) | 95.8 (1242) | 96.9 (622) | 0.312 |
Rales (%) | 63 (826) | 58.3 (378) | 0.051 |
Edema (%) | 67.8 (890) | 67.4 (438) | 0.881 |
Jugular venous pressure (%) | 40.8 (485) | 41.4 (242) | 0.867 |
Medical history | |||
Hypertension (%) | 80.3 (1054) | 77.4 (503) | 0.153 |
Diabetes mellitus (%) | 45.2 (593) | 46.2 (300) | 0.725 |
Hypercholesterolemia (%) | 51.2 (672) | 52.1 (338) | 0.744 |
Smoking (%) | 21.3 (279) | 19 (123) | 0.25 |
Ischemic heart disease (%) | 70.4 (923) | 67.8 (440) | 0.259 |
Myocardial infarction (%) | 51 (668) | 46.4 (301) | 0.059 |
PCI (%) | 26.4 (343) | 25.3 (163) | 0.671 |
CABG (%) | 21.2 (276) | 21.8 (140) | 0.804 |
Peripheral vascular disease (%) | 11.4 (149) | 9.6 (62) | 0.256 |
Atrial fibrillation (%) | 53.2 (696) | 57 (366) | 0.125 |
NYHA class | 0.18 | ||
I/II | 15.8 (208) | 19.2 (125) | |
II | 48.9 (642) | 46.9 (305) | |
IV | 29.9 (393) | 28.9 (188) | |
ICD therapy (%) | 16.1 (212) | 15.3 (99) | 0.658 |
CRT therapy (%) | 10.2 (134) | 9.6 (62) | 0.717 |
Stroke (%) | 9 (118) | 9.2 (60) | 0.926 |
COPD (%) | 19.9 (261) | 19.8 (128) | 0.983 |
Prior medication use | |||
ACE inhibitors or ARB (%) | 76.2 (1000) | 74.6 (485) | 0.469 |
Beta blockers (%) | 76.7 (1006) | 76.5 (497) | 0.961 |
Mineralocorticoid receptor antagonists (%) | 44.6 (585) | 43.4 (282) | 0.648 |
Calcium antagonists (%) | 15 (196) | 10.6 (69) | 0.01 |
Nitrates (%) | 26.9 (353) | 23.6 (153) | 0.126 |
Digoxin (%) | 27.5 (361) | 30.3 (197) | 0.216 |
Laboratory values | |||
Creatinine (mg/dL) | 1.4 [1.1–1.8] | 1.3 [1.1–1.7] | 0.135 |
Creatinine clearance (mL/min) | 48.6 [36.4–62.9] | 49.8 [37.8–64.9] | 0.16 |
Blood urea nitrogen (mg/dL) | 30 [22–41] | 29 [22–41] | 0.303 |
Sodium (mmol/L) | 140 [137–142] | 140 [137–142] | 0.265 |
Potassium (mmol/L) | 4.2 [3.9–4.7] | 4.2 [3.9–4.6] | 0.64 |
Hemoglobin (g/dL) | 12.7 ± 2 | 12.6 ± 1.9 | 0.527 |
Anemia (%) | 42 (487) | 43.5 (254) | 0.592 |
Total cholesterol (mmol/L) | 3.8 ± 1.1 | 3.8 ± 1.1 | 0.59 |
Triglycerides (mmol/L) | 101.3 ± 54.1 | 101.9 ± 57.9 | 0.813 |
BNP (pg/mL) | 442.8 [250.5–789.9] | 458.6 [259.5–829.3] | 0.537 |
Treatment Heterogeneity of Rolofylline
Clinical Characteristics
Biomarkers
Identifying Responders and Nonresponders to Rolofylline
Plasma biomarker |
β-coefficient | Points |
---|---|---|
TNF-R1α ≥4.00 ng/mL | 0.49 | 1 |
ST-2 ≥5.77 ng/mL | 0.48 | 1 |
WAP-4C ≥26.92 ng/mL | 0.29 | 1 |
Total cholesterol ≤3.93 mmol/L | 0.45 | 1 |
Total points |
4
|
Total points | Hazard ratio | 95% confidence interval |
p value |
---|---|---|---|
0 |
Reference group
| ||
1 | 1.17 | 0.76–1.80 | 0.482 |
2 | 1.69 | 1.10–2.60 | 0.017 |
3 | 2.38 | 1.56–3.63 | <0.001 |
4 | 4.81 | 3.11–7.19 | <0.001 |
Total points | Hazard ratio | 95% confidence interval |
p value |
---|---|---|---|
0 | 5.52 | 1.68–18.13 | 0.005 |
1 | 1.35 | 0.76–2.40 | 0.306 |
2 | 0.74 | 0.44–1.24 | 0.249 |
3 | 1.14 | 0.67–1.94 | 0.639 |
4 | 0.61 | 0.40–0.92 | 0.019 |