Table 2. Primary and Secondary End Pointsa.
| End point | Median (25th to 75th) | R, OR, or difference between groups (95% CI)b | P value | |
|---|---|---|---|---|
| Sacubitril/valsartan (n = 167) | Valsartan (n = 168) | |||
| Primary efficacy end point | ||||
| NT-proBNP AUC, median (IQR) | 1.08 (0.75 to 1.60) | 1.19 (0.91 to 1.64) | 0.95 (0.84 to 1.08) | .45 |
| No. | 155 | 158 | NA | NA |
| Secondary efficacy end points | ||||
| Days alive, out of hospital, and free from HF events, median (IQR)c | 147.0 (9.0 to 164.0) | 157.0 (53.5 to 164.0) | −11.2 (−26.4 to 4.0) | .15 |
| Secondary tolerability end points | ||||
| Last dose of sacubitril/valsartan vs valsartan taken before the end of study, No. (%) | ||||
| 0 vs 0 mgd | 49 (29) | 37 (22) | 1.14 (0.78 to 1.68) | .51 |
| 50 vs 40 mg | 28 (17) | 41 (24) | ||
| 100 vs 80 mg | 33 (20) | 30 (18) | ||
| 200 vs 160 mg | 57 (34) | 60 (36) | ||
| Total daily study drug dose (including those receiving study drug), median (IQR), mg | 178.4 (100.0 to 331.3) | 138.6 (80.9 to 263.7) | NA | NA |
| Hypotension, No. (%)e | 29 (17) | 20 (12) | 1.55 (0.84 to 2.87) | .16 |
| Worsening kidney function, No. (%)f | 7 (4) | 7 (4) | 0.99 (0.34 to 2.91) | .99 |
| Hyperkalemia, No. (%)g | 28 (17) | 15 (9) | 2.05 (1.05 to 4.00) | .04 |
| Disease-related events, No. (%) | ||||
| Dysrhythmiah | 23 (14) | 26 (15) | 0.87 (0.48 to 1.60) | .65 |
| Acute coronary syndromei | 3 (2) | 0 | NA | NA |
| Stroke or transient ischemic attackj | 4 (2) | 1 (1) | 4.10 (0.45 to 37.06) | .14 |
| Angioedema | 0 | 1 (1) | NA | NA |
Abbreviations: AUC, area under the curve; CV, cardiovascular; HF, heart failure; NA, not applicable; NT-proBNP, N-terminal pro–brain natriuretic peptide; OR, odds ratio; R, ratio of change.
SI conversion factor: To convert potassium to millimoles per liter, multiply by 1.
All outcomes were assessed from baseline through 24 weeks.
The AUC data are presented as median (IQR) where a ratio of change; the days alive, out of the hospital, and free from HF events represent a treatment difference; and all of the end points are shown as ORs for sacubitril/valsartan compared with valsartan.
Defined as listing for cardiac transplant (status 1-4), heart transplant, left ventricular assist device implantation, or use of continuous inotropic therapy for 7 days or more, or hospitalization for HF on 2 or more occasions (other than the index admission).
The patient stopped study drug early or therapy with the study drug was never started.
Defined as systolic blood pressure less than or equal to 85 mm Hg.
Defined as estimated glomerular filtration rate less than 20 mL/min/1.73 m2 between randomization and week 24.
Defined as potassium level greater than or equal to 5.5 mEq/L.
Defined as new and clinically significant atrial or ventricular dysrhythmias.
Defined as unstable angina, non–ST-segment elevation myocardial infarction, and ST-segment elevation myocardial infarction.
Defined as cerebrovascular accidents (stroke) or any cause of (hemorrhage, ischemic, embolic) cerebrovascular accident and transient ischemic attack. There were 2 patients in the sacubitril/valsartan arm treatment who experienced a cerebrovascular event 30 days after left ventricular assist device implantation that were censored and not included in this table.