PCSK9 inhibitors in atherosclerotic cardiovascular disease

Registration and administrative information (PROSPERO field set)

Extracted values, and where each came from

One row per extracted value. Every row carries the value, the verbatim sentence it was read from, a resolvable link to the source, and whether the number was read or derived. Where any of those is absent the row says so rather than omitting the value.

References

Included studies

• — https://clinicaltrials.gov/study/NCT01663402
• — https://clinicaltrials.gov/study/NCT01764633

Regulatory documents

Methods and guidance

Sources

Risk of bias

⬇ SVG (vector) 1 KB

Only the vector format is offered for this figure, by choice: it is line art — discrete marks, glyphs and labels — which SVG reproduces exactly at any size, so a raster would add weight without adding fidelity. The build was able to rasterise; it was asked not to.

Not drawn, because there is nothing to draw it from.

GOSH

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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 9091822e99aa8781), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.

Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — gosh.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — gosh.tiff, 5,537 KB.

Deliberately not drawn. Every subset meta-analysis of 2 trials is 3 points; a cloud that small cannot show the multimodality GOSH exists to reveal, and a reader would take the picture as evidence of its absence.

Trial-sequential analysis

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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 25ed9800fdf56614), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.

Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — tsa.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — tsa.tiff, 6,665 KB.

TSA boundaries depend entirely on a target information size that must be pre-specified. This review's protocol registers none, so any boundary drawn here would be a parameter chosen after seeing the data -- which is the practice TSA exists to protect against.

Meta-regression

⬇ SVG (vector) 1 KB ⬇ PNG 3500x540 87 KB

All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: e35ec93bbc9a1c10), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.

Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — bubble.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — bubble.tiff, 5,537 KB.

The protocol pre-specifies no moderator, and at k = 2 a meta-regression would be fitted on 2 points. Not drawn rather than drawn with a caveat: a bubble plot invites reading a slope, and there is no slope here that any reader should read.

Summary of findings

1. The pooled estimate for this outcome has been WITHDRAWN, so there is no estimate for a certainty rating to be about. Any rating this object still carries for this outcome was made about the withdrawn estimate and is not shown beside it.
2. Read this beside `whether the estimand was established`. That flag records that every contributing trial measures the same quantity. It records nothing about what that quantity was measured against -- whether the comparators are of one kind, whether each comparison was randomised, whether it was concurrent. The two questions were never separated. Named as P48 in PAGE-STANDARD.md v1.21.0 and swept by scripts/audit_mixed_contrast_pools.py.

Reproducibility artifact

This page CANNOT be rebuilt from what is recorded here: no canonical object is recorded and no registered commit is recorded. Each figure on the Analysis tab downloads as an SVG carrying exactly the values shown.

Other recorded qualifications

Statements this review records about the limits of what it establishes, which are not shown elsewhere on this page. They are reproduced from the object verbatim and are not summarised.

Paper

Each statement below cites the record it came from; those sources are listed at the end of every section. Where the record holds nothing, the section says so by name rather than being left out, so a procedure that was not carried out can be told from one that simply was never mentioned.

Title

PCSK9 inhibitors in atherosclerotic cardiovascular disease¹

Abstract

Question. In Multiple trial-declared outcomes: Time to Cardiovascular Death, Myocardial Infarction, Hospitalization for Unstable Angina, Stroke, or Coronary Revascular | Time to First Occurrence of Major Adverse Cardiovascular Event (MACE); Percentage of Observed Participants With Outcome, what do the contributing trials show?¹

Introduction

Background. This review asks: In Multiple trial-declared outcomes: Time to Cardiovascular Death, Myocardial Infarction, Hospitalization for Unstable Angina, Stroke, or Coronary Revascular | Time to First Occurrence of Major Adverse Cardiovascular Event (MACE); Percentage of Observed Participants With Outcome, what do the contributing trials show? It examines 2 randomised trials and does not pool them. The outcome sought is Multiple trial-declared outcomes: Time to Cardiovascular Death, Myocardial Infarction, Hospitalization for Unstable Angina, Stroke, or Coronary Revascular | Time to First Occurrence of Major Adverse Cardiovascular Event (MACE); Percentage of Observed Participants With Outcome.¹

Methods — search

Primary trials. No bibliographic search for primary trials was run. The 2 included trials were identified by reading named registrations on the dates recorded on each entry. The basis on which this object was verified is not recorded. What this object does not claim is not recorded. The bar this object had to clear is not recorded.¹

Methods — eligibility criteria

not recorded on the page this object was extracted from¹

Methods — outcomes sought at every registered rank

Every registered rank -- primary, secondary and other -- was read for 2 of 2 contributing trials before any decision about which outcomes could be combined; each records the time it was read.¹

Results

Multiple trial-declared outcomes: Time to Cardiovascular Death, Myocardial Infarction, Hospitalization for Unstable Angina, Stroke, or Coronary Revascular | Time to First Occurrence of Major Adverse Cardiovascular Event (MACE); Percentage of Observed Participants With Outcome . These 2 trials are not pooled, and the reason is stated rather than the outcome being quietly omitted: Two composites, not one estimand. Registered primaries read from ClinicalTrials.gov 2026-08-19. Fourier (NCT01764633, n=27,564) registers 'Time to Cardiovascular Death, Myocardial Infarction, Hospitalization for Unstable Angina, Stroke, or Coronary Revascularization'. Odyssey outcomes (NCT01663402, n=18,924) registers 'Time to First Occurrence of Major Adverse Cardiovascular Event (MACE)', defined in its own description as CHD death, non-fatal MI, fatal and non-fatal ischaemic stroke, or unstable angina requiring hospitalisation. They differ on three axes: fourier counts all cardiovascular death against odyssey's CHD death; Fourier counts all stroke against odyssey's ischaemic stroke; and fourier counts coronary revascularisation, which odyssey does not. Revascularisation is the highest-frequency component in this class of trial, so this is not a rounding difference in the event definition -- it changes what is being counted. P37: composite names are not definitions. Separately, the estimator was DerSimonian-Laird at k=2, and DL is refused below k=10 in this project because its tau-squared is badly biased with few studies. And the object already said so: it carried estimand_established=false and a the recorded reason this pool was declined stating the estimate had been recovered from the page rather than established. Authority: mecir Box 10.10.a C62 -- undertake or display a meta-analysis only if participants, interventions, comparisons and outcomes are judged sufficiently similar to ensure a clinically meaningful answer.¹

Disagreements between sources

not recorded on the page this object was extracted from¹

not recorded on the page this object was extracted from²

Limitations

What this review does not give a clinician: the number of events in each arm and any absolute effect or number needed to treat. A relative effect cannot be turned into the benefit or the risk facing one patient without them, so this review can support a judgement about what these trials found and not a judgement about what to do.¹

Reporting guidelines

This review reports against PRISMA 2020. A screening record is held on this object and the flow it supports is shown in the Methods. The completed PRISMA checklist and FLOW diagram are not held here: the venue requires them deposited in an approved repository with a DOI cited in the Data Availability Statement, and minting that DOI is an author action rather than a build step.¹

Note on registration

No PROSPERO registration or protocol record is held on this object. That is not the same as knowing this review was not registered, and neither claim is made. It is recorded here as an absence so that a reader does not have to infer it from silence.¹

References

Figure legends

Figures

Trial characteristics

Notes on this record — sections not written, and why

Of the four properties this project requires of a completed topic, 0 are held (none) and 4 are refused with the obstacle named in the evidence (the number of published syntheses this review was a GRADE certainty rating for each pooled outcome, the statistical model's output, quoted as it was produced, a risk-of-bias judgement for each reported result).¹

Not reported in this record

The items below were not written because the record does not hold what they would be composed from. They are named here so that an absence is not mistaken for an omission.