Evidence mapPaperPMID 35543701Full record

Trial reportCirculation. Genomic and precision medicine2022

Pharmacogenomic Study of Statin-Associated Muscle Symptoms in the ODYSSEY OUTCOMES Trial.

William A Murphy, Nan Lin, Amy Damask, Gregory G Schwartz, P Gabriel Steg, Michael Szarek, Poulabi Banerjee, Sergio Fazio, Garen Manvelian, Robert Pordy and 2 more

Open access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Circulation. Genomic and precision medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 2 pooled it
2.2field-weighted citation impact, top 13% of its field
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

6 citing papers in PubMed, 2 syntheses or guidelines pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Article
  6. Article
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

12 authors at 5 institutions in 2 countries.

William A MurphyDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill' Chapel Hill' NC (W.A.M.).ORCID 0000-0002-7476-9248
Nan LinRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY (N.L., A.D., P.B., S.F., G.M., R.P., A.R.S., C.P.).
Amy DamaskDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill' Chapel Hill' NC (W.A.M.).
Gregory G SchwartzUniversity of Colorado School of Medicine, Aurora' CO (G.G.S., M.S.).ORCID 0000-0003-2954-0695
P Gabriel StegUniversité de Paris, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris' INSERM U1148, France (P.G.S.).ORCID 0000-0001-6896-2941
Michael SzarekUniversity of Colorado School of Medicine, Aurora' CO (G.G.S., M.S.).ORCID 0000-0002-0046-0264
Poulabi BanerjeeRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY (N.L., A.D., P.B., S.F., G.M., R.P., A.R.S., C.P.).ORCID 0000-0001-5304-9543
Sergio FazioRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY (N.L., A.D., P.B., S.F., G.M., R.P., A.R.S., C.P.).ORCID 0000-0002-8145-8034
Garen ManvelianRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY (N.L., A.D., P.B., S.F., G.M., R.P., A.R.S., C.P.).
Robert PordyRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY (N.L., A.D., P.B., S.F., G.M., R.P., A.R.S., C.P.).ORCID 0000-0002-8001-6795
Alan R ShuldinerRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY (N.L., A.D., P.B., S.F., G.M., R.P., A.R.S., C.P.).ORCID 0000-0001-9921-4305
Charles PauldingRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY (N.L., A.D., P.B., S.F., G.M., R.P., A.R.S., C.P.).ORCID 0000-0002-7918-3561
Regeneron (United States) · USUniversity of North Carolina at Chapel Hill · USColorado School of Public Health · USInserm · FRUniversity of Colorado Denver · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundStatin-associated muscle symptoms (SAMS) are the most frequently reported adverse events for statin therapies. Previous studies have reported an association between the p.Val174Ala missense variant in

methodsODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; n=18 924) was a double-blind, randomized, placebo-controlled study evaluating the efficacy and safety of alirocumab (a PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitor) in acute coronary syndrome patients receiving high-intensity statin therapy. The goal of this pharmacogenomic analysis was to identify genetic variants associated with atorvastatin- and rosuvastatin-mediated SAMS among ODYSSEY OUTCOMES subjects who consented to participate in the genetic study (n=11 880). We performed multi-ancestry exome-wide and genome-wide association studies and gene burden analysis across 2 phenotypes (clinical SAMS [n=10 617] and creatine kinase levels [n=9630]).

resultsA novel genome-wide significant association for an intronic variant (rs6667912) located within

conclusionsThis study comprises the largest discovery exome-wide and genome-wide association study for atorvastatin- or rosuvastatin-mediated SAMS to date. These novel genetic findings may provide biological/mechanistic insight into this drug-induced toxicity, and help identify at-risk patients before selection of lipid-lowering therapies.

Indexed as

Acute Coronary SyndromeAtorvastatinHydroxymethylglutaryl-CoA Reductase InhibitorsMusclesRosuvastatin CalciumAntigens, CDCholesterol, LDLCreatine KinaseGenome-Wide Association StudyHumansMembrane ProteinsPCSK9 InhibitorsPharmacogenomic TestingReceptors, ImmunologicAntigens, CDAtorvastatinCholesterol, LDLCreatine KinaseHydroxymethylglutaryl-CoA Reductase InhibitorsLILRB5 protein, humanMembrane ProteinsPCSK9 InhibitorsReceptors, ImmunologicRosuvastatin CalciumTMEM9 protein, humanacute coronary syndromeatorvastatincreatine kinasedrug-related side effects and adverse reactionsgenome-wide association studypharmacogeneticsrosuvastatin calcium

Identifiers

PMID35543701
PMCPMC9213083
OpenAlexW4280500521

What Socratic holds

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Registered trials

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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 Socratic graph.