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Cited by 114Pharmacovigilance and Adverse Drug ReactionsLipoproteins and Cardiovascular HealthDrug-Induced Adverse Reactions

Statin‐Associated Muscle‐Related Adverse Effects: A Case Series of 354 Patients

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Cham, Stephanie, Evans, Marcella A., Denenberg, Julie O., Golomb, Beatrice A.·2010·Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
DOI 10.1592/phco.30.6.541PMC PMC4729295
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Abstract

STUDY OBJECTIVE: To characterize the properties and natural history of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin)-associated muscle-related adverse effects (MAEs). DESIGN: Patient-targeted postmarketing adverse-effect surveillance approach coupling survey design with an open-ended narrative. SETTING: University-affiliated health care system. SUBJECTS: Three hundred fifty-four patients (age range 34-86 yrs) who self-reported muscle-related problems associated with statin therapy. MEASUREMENTS AND MAIN RESULTS: Patients with perceived statin-associated MAEs completed a survey assessing statin drugs and dosages; characteristics of the MAEs; time course of onset, resolution, or recurrence; and impact on quality of life (QOL). Cases were assessed for putative drug adverse-effect causality by using the Naranjo adverse drug reaction probability scale criteria and were evaluated for inclusion in groups for which mortality benefit with statins has been shown. Patients reported muscle pain (93%), fatigue (88%), and weakness (85%). Three hundred patients (85%) met literature criteria for probable or definite drug adverse-effect causality. Ninety-four percent of atorvastatin usages (240/255) generated MAEs versus 61% of lovastatin usages (38/62, p<0.0001). Higher potency statins reproduced MAEs in 100% of 39 rechallenges versus 73% (29/40) with lower potency rechallenges (p<0.01). Time course of onset after statin initiation varied (median 14 wks); some MAEs occurred after long-term symptom-free use. Recurrence with rechallenge had a significantly shorter latency to onset (median 2 wks). The MAEs adversely affected all assessed functional and QOL domains. Most patients with probable or definite MAEs were in categories for which available randomized controlled trial evidence shows no trend to all-cause mortality benefit with statin therapy. CONCLUSION: This study complements available information on the properties and natural history of statin-associated MAEs, affirming dose dependence and strong QOL impact. The data indicating a dose-dependent relationship between MAE risk and recurrence suggest lower potency statins or discontinuation may bear consideration for ameliorating symptoms.

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Authors
Cham, S., Evans, M. A., Denenberg, J. O., & Golomb, B. A.
Affiliations
University of California San Diego (US)
Corresponding author
Golomb, Beatrice A.
ORCID
Venue
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
Publisher
Wiley
Published
2010-06
Volume
30
Issue
6
Pages
541-553
ISSN
  • 0277-0008 (ISSN-L)
  • 1875-9114
DOI
10.1592/phco.30.6.541
PMC
PMC4729295
OpenAlex
W2016598185
Cited by
114
References
10
Citations by year
2026: 2 · 2025: 4 · 2024: 3 · 2023: 8 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 7 · 2017: 8 · 2016: 17 · 2015: 5 · 2014: 13 · 2013: 12 · 2012: 7
FWCI
11.58
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 584 d)
Locations
  • Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • University of California, San Diego
  • National Heart, Lung, and Blood Institute (R01HL063055)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
Keywords
statin adverse effects, statin-induced myopathy, statins, atorvastatin, lovastatin, statin potency, drug rechallenge, quality of life, fatigue, myalgia, mortality benefit
MeSH terms
Adult, Aged, Aged, 80 and over, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Pain, Product Surveillance, Postmarketing, Quality of Life, Recurrence, Time Factors, Adverse Drug Reaction Reporting Systems, Muscle Fatigue, Muscle Weakness, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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