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Plasma statin concentrations do not correlate with statin-induced myalgia

2024· article· en· W4403819152 on OpenAlexaffabout
Markus Ritvos, G. Mombelli, Markus Ramste, Mitja Lääperi, Dimple Kauhanen, Juha Sinisalo, C.R. Sirtori, Paul D. Thompson, Michael P. Dubé, Jean‐Claude Tardif, Reijo Laaksonen

Bibliographic record

VenueEuropean Heart Journal · 2024
Typearticle
Languageen
FieldMedicine
TopicLipoproteins and Cardiovascular Health
Canadian institutionsUniversité de Montréal
Fundersnot available
KeywordsMedicinemyalgiaStatinHydroxymethylglutaryl-CoA Reductase InhibitorsInternal medicineCardiologyPharmacology

Abstract

fetched live from OpenAlex

Abstract Aims Statins are essential in cardiovascular prevention. Although well-tolerated, patient adherence is often suboptimal due to experienced musculoskeletal symptoms ranging from mild myalgia to rare life-threatening rhabdomyolysis. This study aimed to investigate the relationship between plasma concentrations of statin metabolites in patients experiencing myalgia without rhabdomyolysis. Methods and results Plasma concentrations of statin metabolites were quantitatively assessed using mass spectrometry across three case-control cohorts evaluating statin-induced myalgia. The analysis included a total of 373 patients from the MILANO study (N=85 with self -reported myalgia), the MONTREAL study (N=248 with clinically verified myalgia) and the STOMP study (N=40 with rechallenge-verified statin-induced myalgia). STOMP found no significant difference in the plasma concentrations of statin metabolites between statin naïve patients with myalgia (N=12) taking atorvastatin 80 mg daily and asymptomatic controls (N=28), including upon subsequent statin rechallenge. Both the MILANO and MONTREAL studies showed lower plasma concentrations of statin metabolites in patients with myalgias compared to controls. MILANO showed a significant difference in rosuvastatin lactone concentration in patients with myalgias compared to asymptomatic controls (P = 0.025). Similarly, MONTREAL showed significantly lower mean atorvastatin metabolite concentrations in affected patients versus controls (P values ranging from 0.0073 to 0.037). Atorvastatin dosages in MONTREAL ranged from 5 to 80 mg daily, the most frequent regimens being 20 mg (27% in cases; 24% in controls) and 40 mg (33% in cases; 37% in controls). Creatine kinase levels were measured in all cohorts and were not different between cases and controls. Conclusion Development of myalgias in patients with normal creatine kinase levels is not associated with higher statin metabolite plasma concentrations. Myalgias during statin therapy are not caused by pharmacokinetic abnormalities.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.035
GPT teacher head0.294
Teacher spread0.260 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2024
Admission routes2
Has abstractyes

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