Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure
New England Journal of Medicine, 2014 · paper · Clinical trials
A double-blind trial of 8,442 heart failure patients comparing LCZ696 with enalapril. Stopped early, it found fewer deaths from cardiovascular causes or heart failure hospitalizations with LCZ696 (21.8% versus 26.5%).
3 findings
Reference or label Table 2 footnote † says "The treatment effect is shown as the least-squares mean (±SE) of the between-group difference", but the between-group difference is printed with a 95% CI ("1.64 (0.63–2.65)") and the ± values ("−2.99±0.36", "−4.63±0.36") are per-group changes.
- p. 7 Table 2, footnote †
The treatment effect is shown as the least-squares mean (±SE) of the between-group dif-
- p. 7 Table 2, row 'Change in KCCQ clinical summary score at 8 mo'
−2.99±0.36
- p. 7 Table 2, row 'Change in KCCQ clinical summary score at 8 mo'
1.64 (0.63–2.65)
Only the authors can say what is right here.
Judge's note: Viewed Table 2 and its footnotes on p7. The ±0.36 values sit in the two group columns, and the difference column carries a confidence interval, not a standard error. The SE implied by the CI is about 0.52, not 0.36, so ±0.36 is the per-group SE (0.36 * 1.414 = 0.51 is consistent with that). The footnote attaches "(±SE)" to the wrong quantity and never says what ± means in the group columns.
Second check: another model agreed
Report a problem with this finding
Reference or label "the findings in earlier trials of omapatrilat.18,22" cites reference 22, which is "Solomon SD, Zile M, Pieske B, et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial", not an omapatrilat trial.
- p. 11 Discussion, left column, paragraph on safety
and with the findings in earlier trials of omapa-
- p. 12 Reference 22
The angiotensin receptor neprilysin in-
- p. 11 Discussion, left column, safety paragraph
with the findings in earlier trials of omapatrilat.18,22
- p. 12 Reference 22
The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial
Only the authors can say what is right here.
Judge's note: The superscript reads 18,22 on the p11 image. In the reference list (p12), reference 18 is OVERTURE (omapatrilat vs enalapril) and reference 22 is by its own title a trial of LCZ696. The other omapatrilat trial in the list is reference 17 (OCTAVE). Either the reference number is wrong (17 intended) or the sentence should read trials of omapatrilat and LCZ696; only the authors can say which. Verified entirely from the paper's own reference list.
Second check: another model agreed · checked by hand
Report a problem with this finding
Wording Methods say "Cox proportional-hazards models, with treatment and region as fixed-effect factors; hazard ratios, 95% confidence intervals, and two-sided P values were calculated with the use of the Cox models", but the Table 2 footnote says "Hazard ratios were calculated with the use of stratified Cox proportional-hazard models. P values ... were calculated by means of a stratified log-rank test".
- p. 7 Statistical Analysis (continued from p 6), left column
hazards models, with treatment and region as
- p. 7 Statistical Analysis, left column
intervals, and two-sided P values were
- p. 7 Table 2, footnote *
means of a stratified log-rank test without adjustment for multiple comparisons
Only the authors can say what is right here.
Judge's note: Read both passages on the p7 image. The methods describe region as a fixed-effect factor and P values from the Cox model; the footnote describes stratified models and a stratified log-rank P value, a test the Statistical Analysis section never mentions. No statement in the article reconciles the two descriptions. The numbers would be near-identical either way, so this is a description inconsistency that only the authors can settle. It may also be the source of the 0.83/0.84 difference in C010.
Second check: another model agreed
Report a problem with this finding
5 minor (typos and the like; most checked by the judge only)
Wording Figure 1 is titled "Screening Criteria, Run-in Periods, and Randomization." but the flow diagram and legend contain no screening step, number screened or screening criteria.
- p. 3 Figure 1 title
Screening Criteria, Run-in Periods, and Randomization.
Judge's note: Viewed Figure 1 on p3. The diagram starts at "10,513 Patients entered enalapril run-in phase" and shows only the two run-in phases, randomization and the post-randomization exclusions. The legend does not cover screening either. The title's first element has no counterpart in the figure; a minor labelling point.
Second check: another model agreed
Report a problem with this finding
Wording Text says "Four patients (two in each group) did not start the study medication and were excluded from the safety analyses", but Table 3 (adverse events) is headed "(N = 4187)" and "(N = 4212)", the full randomized groups.
- p. 9 Results, Safety, first sentence
Four patients (two in each group) did not start
- p. 10 Table 3, column headers
(N = 4187)
- p. 10 Table 3, column headers
(N = 4212)
Judge's note: Viewed the Safety text (p9) and Table 3 (p10). The safety population should be 4185 and 4210. The printed percentages are the same with either denominator (for example 588/4187 = 14.04% and 588/4185 = 14.05%), so no table value is demonstrably wrong; only the header N conflicts with the text.
Second check: another model agreed
Report a problem with this finding
Typo Figure 3 heads the same column "Hazard Ratio (95% CI)" in the Primary End Point panel and "Hazard ratio (95% CI)" in the Death from Cardiovascular Causes panel.
- p. 8 Figure 3, header of the Primary End Point panel
Hazard Ratio
Judge's note: Viewed Figure 3 on p8. The left panel header has a capital R and the right panel a lowercase r. Purely cosmetic.
Second check: none (judge only)
Report a problem with this finding
Typo Missing comma in "(0.95 points; 95% CI 0.31 to 1.59)"; elsewhere the paper writes "95% CI, 0.63 to 2.65".
- p. 9 Study Outcomes, KCCQ paragraph
(0.95 points; 95% CI 0.31 to 1.59)
Judge's note: Viewed p9. The comma after "95% CI" is absent in this one instance, while the same paragraph and the rest of the article use "95% CI, x to y". Cosmetic.
Second check: none (judge only)
Report a problem with this finding
Typo Reference 13 prints "Interactions between angiotensin ll and atrial natriuretic peptide" with two lowercase letter l's in place of the Roman numeral "II".
- p. 12 Reference 13
tions between angiotensin ll and atrial
- p. 12 Reference 13
Interactions between angiotensin ll and atrial natriuretic peptide
Judge's note: Viewed the reference-list crop of page 12. In reference 13 the two characters after "angiotensin" are thin, ascender-height strokes without serifs, matching the lowercase l in "renomedullary" just below. In reference 21 in the same crop, "angiotensin II receptor" shows capital I glyphs with serifs. The text layer agrees: "ll" in reference 13, "II" in references 15 and 21 and in the body text. This is a typesetting error in the published PDF, not an extraction artefact; the fix is "angiotensin II".
Second check: none (judge only)