Evidence map›Paper›PMID 31599200›Full record

Trial reportJournal of the American Heart Association2019

Mortality Benefit of Alirocumab: A Bayesian Perspective.

Christopher Labos, James M Brophy, Allan Sniderman, George Thanassoulis

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Journal of the American Heart Association, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Mortality Benefit of Alirocumab: A Bayesian Perspective.Journal of the American Heart Association · 2019
    Trial
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Christopher LabosMcGill University Health Center Montreal Canada.
James M BrophyMcGill University Health Center Montreal Canada.
Allan SnidermanMcGill University Health Center Montreal Canada.
George ThanassoulisMcGill University Health Center Montreal Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background The ODYSSEY OUTCOMES (Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome) trial demonstrated that alirocumab reduced major cardiovascular events. However, because of the hierarchical testing strategy used for the multiple outcomes examined, the observed reduction in all-cause mortality was labeled "nominally significant" which has clouded its interpretation. Methods and Results We re-analyzed data from ODYSSEY OUTCOMES using Bayesian methods and generated various prior probabilities by incorporating mortality data from previous similar PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor trials. We first used data from the ODYSSEY OUTCOMES trial with a non-informative prior, then sequentially added data from ODYSSEY LONG TERM and the FOURIER trial, giving FOURIER full weight, 50% weight and 10%. The posterior probability of a mortality reduction using only the ODYSSEY OUTCOMES data was hazard ratio 0.85 (95% CI 0.74-0.99) which corresponded to a 98.4% probability of a mortality benefit. When the ODYSSEY LONG TERM data were added to the analysis, the posterior probability was hazard ratio 0.84 (95% CI 0.72-0.97) with a 99.9% probability of mortality reduction, and when the FOURIER data were added to the analysis the posterior probability was hazard ratio 0.94 (95% CI 0.85-1.04) with an 89.1% probability of a mortality reduction. When the FOURIER trial was given only 50% or 10% weight, the probability of a mortality reduction rose 95.4% and 98.7%, respectively. We estimate that the probability of >1% absolute risk reduction ranges from 8% to 24%, while the probability of >0.5% absolute risk reduction ranges from 66% to 89%. Conclusions Our analysis demonstrates a high likelihood that alirocumab confers a reduction in all-cause mortality, despite the equivocal interpretation of the data in the original ODYSSEY OUTCOMES publication.

Indexed as

Acute Coronary SyndromeAntibodies, Monoclonal, HumanizedBayes TheoremBiomarkersCanadaCause of DeathCholesterol, LDLDose-Response Relationship, DrugHumansPrognosisSurvival RatealirocumabAntibodies, Monoclonal, HumanizedBiomarkersCholesterol, LDLBayesiancholesterolmortalityPCSK9

Identifiers

PMID31599200
PMCPMC6818032

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.