Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome
2018 · paper · Clinical trials
A randomized placebo-controlled trial of alirocumab, a PCSK9-blocking antibody, in 18,924 patients who had an acute coronary syndrome and were on high-intensity statins. Composite cardiovascular events occurred in 9.5% versus 11.1% on placebo.
5 findings
Substance The number of patients randomized in China is printed two ways: Methods "In China, 614 patients underwent randomization" and Results "In China, 613 patients underwent randomization".
- p. 3 Methods, Statistical Analysis, right column
In China, 614 patients underwent randomization
- p. 4 Results, Patients, Trial Regimen, and Follow-up
In China, 613 patients under-
- p. 4 Results, Patients
In China, 613 patients under-went randomization
Only the authors can say what is right here.
Judge's note: Viewed pages 3 and 4; both numbers are as quoted on the page images. Both sentences describe the same event (randomization in China after the main cohort). A search of the article text for 'China' found no statement distinguishing two populations. The Methods sentence points to the Supplementary Appendix, which is not among the files, so which figure is right cannot be settled here.
Second check: another model agreed
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Substance Table 1, index acute coronary syndrome, Missing data row prints "19 (<0.1)" and "12 (<0.1)" with N=9462 per group; 19/9462 is 0.2% and 12/9462 is 0.1%.
- p. 5 Table 1, Index acute coronary syndrome, Missing data row
19 (<0.1)
- p. 5 Table 1, Index acute coronary syndrome, Missing data row, placebo
12 (<0.1)
Judge's note: Viewed Table 1 on page 5. Both cells read '(<0.1)'. The four rows of the block sum to 9462 in each arm, so the denominator is the column N. The computed percentages are 0.20% and 0.13%, neither below 0.1. The other three rows sum to 99.8% and 99.9%, leaving 0.2 and 0.1. Table 3 on page 9 uses '<0.1' for 9/9451 (0.095%) and prints 0.2 for 16/9443, so the journal's convention does not explain it. No footnote gives another denominator. The effect is small (a baseline missing-data row), but the printed values are wrong.
Second check: another model agreed
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Reference or label Reference 12 (Sabatine et al., evolocumab, N Engl J Med 2015) is cited for the bococizumab/SPIRE finding in two places: "with one agent showing benefit only among patients who had a baseline LDL cholesterol level of at least 100 mg per deciliter (2.6 mmol per liter).12" and "Both our trial and the SPIRE trial showed ... LDL cholesterol level of 100 mg or more per deciliter.12"; SPIRE is reference 13.
- p. 2 Introduction, second paragraph
deciliter (2.6 mmol per liter).12
- p. 9 Discussion, right column
LDL cholesterol level of 100 mg or more per deci- liter.12
- p. 11 Reference list, entry 12
12. Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events.
- p. 11 Reference list, entry 12
Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372:1500-9.
Judge's note: Viewed pages 2, 9 and 11. Both superscripts read 12 on the page images. Reference 12 in the list is 'Efficacy and safety of evolocumab in reducing lipids and cardiovascular events' (2015). Reference 13 is Ridker et al., bococizumab in high-risk patients. The Discussion itself says SPIRE evaluated bococizumab and cites FOURIER and SPIRE as '11,13'. So the SPIRE statements should cite 13, not 12. This is settled from the paper's own text and reference list.
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Reference or label "alirocumab, a fully human monoclonal antibody to PCSK9,13-15" cites a range that includes reference 13 (Ridker, bococizumab) and reference 15 (Gail and Simon, a 1985 Biometrics paper on qualitative interactions), neither of which concerns alirocumab.
- p. 2 Introduction, last paragraph
man monoclonal antibody to PCSK9,13-15 would
- p. 11 Reference list, entries 13 and 15
15. Gail M, Simon R. Testing for qualitative interactions between treatment effects and patient subsets.
- p. 2 Introduction
monoclonal antibody to PCSK9,13-15 would
- p. 2 Introduction
monoclonal antibody to PCSK9,13-15
Only the authors can say what is right here.
Judge's note: Viewed pages 2 and 11. The superscript is '13-15' on the page image. Reference 13 is the bococizumab trial, 14 is the ODYSSEY OUTCOMES design paper, and 15 is Gail and Simon, which is cited correctly as 15 for the Gail–Simon test in the Statistical Analysis section on page 4. Only 14 fits the statement. The alirocumab papers in the list are 8, 9 and 14, but the intended range cannot be determined from the files, so this is a query for the authors.
Second check: another model agreed
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Reference or label The sentence comparing the current trial with FOURIER ends "LDL cholesterol level was approximately 90 mg per deciliter.10"; reference 10 is Blom et al., "A 52-week placebo-controlled trial of evolocumab in hyperlipidemia", while FOURIER is reference 11.
- p. 9 Discussion, right column
LDL cholesterol level was approximately 90 mg per deciliter.10
- p. 11 Reference list, entry 10
10. Blom DJ, Hala T, Bolognese M, et al. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia.
- p. 11 Reference list, entry 10
A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med 2014;370:1809-19.
- p. 9 Discussion
per deciliter.10
Judge's note: Viewed pages 9 and 11. The superscript is 10 on the page image. Reference 10 is the 52-week evolocumab hyperlipidemia trial (2014). Reference 11 is Sabatine et al., 'Evolocumab and clinical outcomes in patients with cardiovascular disease' (2017), which the paper cites as FOURIER ('FOURIER ... trial,11' on page 8 and '11,13' on page 9). The sentence is about the FOURIER trial's population and outcomes, so 11 is the evident citation.
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3 minor (typos and the like; most checked by the judge only)
Typo A capitalised word follows a semicolon mid-sentence: "(Table 2); The Kaplan–Meier probability estimate".
- p. 6 Results, End Points, first paragraph
(Table 2); The Kaplan–Meier probability estimate
Judge's note: Viewed page 6. The image shows '(Table 2); The Kaplan–Meier', a semicolon followed by a capital T. This is not an extraction artefact. Either the semicolon should be a full stop or 'The' should be lower case.
Second check: none (judge only)
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Typo Company name misspelled in Dr. White's disclosure: "fees for serving on a steering committee from Elsai and DalCor Pharma UK"; the same paragraph spells it "Eisai" in Dr. Bhatt's disclosure.
- p. 10 Disclosures, Dr. White
and fees for serving on a steering committee from Elsai and
- p. 10 Disclosures, Dr. Bhatt
Bristol-Myers Squibb, Eisai, Ethicon, Medtronic
- p. 10 Disclosures, Dr. White
from Elsai and
Judge's note: Viewed page 10 and the enlarged crop. The crop shows 'Elsai' with a tall lower-case l in the White disclosure and 'Eisai' with a dotted i in the Bhatt disclosure. The text layer agrees. The paper's own spelling 'Eisai' elsewhere in the paragraph supplies the fix, so no outside fact is needed.
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Typo Company name inconsistent: Dr. Harrington's disclosure reads "consulting fees from the Medicine Company", while the Schwartz and Bhatt disclosures read "the Medicines Company".
- p. 10 Disclosures, Dr. Harrington
and consulting fees from the Medicine Company
- p. 10 Disclosures, Dr. Schwartz
Roche, the Medicines Company
- p. 10 Disclosures, Dr. Harrington
from the Medicine Company
Judge's note: Viewed page 10 and the enlarged crop. The Harrington disclosure prints 'the Medicine Company'; the Schwartz and Bhatt disclosures in the same paragraph print 'the Medicines Company'. The singular form is a slip against the paper's own usage twice elsewhere.
Second check: none (judge only)