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Rhabdomyolysis with Co-Administration of Statins and Antiplatelet Therapies—Analysis of the WHO Pharmacovigilance Database

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Abstract

Purpose

While statins and antiplatelet therapies are largely prescribed together worldwide, limited information is available on the safety of their association regarding rhabdomyolysis occurrence. We aimed to assess the reporting of rhabdomyolysis in patients treated with a combination of statin and antiplatelet therapy, compared to statin alone.

Methods

We used the World Health Organization pharmacovigilance database (VigiBase®) to compare the rhabdomyolysis reporting between statin (atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin) plus antiplatelet therapy (acetylsalicylic acid, clopidogrel, prasugrel and ticagrelor) groups versus statin alone groups, for each statin and antiplatelet therapy. Study setting was restricted to patients aged 45 or older, including reports up until 1st September, 2021. We computed reporting Odds-Ratio (ROR) and their 95% confidence interval (CI) to quantify the disproportionality between groups, adjusted on age and sex.

Results

Among the 11,431,708 reports of adverse reactions, we extracted 9,489 cases of rhabdomyolysis in patients treated with statins, of whom 2,464 (26%) were also treated with antiplatelet therapy. The reporting of rhabdomyolysis was increased when ticagrelor was associated with atorvastatin (ROR 1.30 [1.02–1.65]) or rosuvastatin (ROR 1.90 [1.42–2.54]) compared to the respective statin alone but did not change when aspirin, clopidogrel or prasugrel were considered.

Conclusion

Rhabdomyolysis reporting was increased when ticagrelor -but not other antiplatelet agents- was notified with the most prescribed statins in practice. This finding needs to be considered by physicians especially in high-risk patients.

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Data Availability

The data underlying this article will be shared on reasonable request to the corresponding author.

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Service de Cardiologie, CHU de Caen Normandie, 14000, Caen, France

    Vincent Roule, Adrien Lemaitre & Farzin Beygui

  2. UMRS 1237, INSERM, GIP Cyceron, 14000, Caen, France

    Vincent Roule & Farzin Beygui

  3. Cardiology department, Caen University Hospital, Avenue Cote de Nacre, 14033, Caen, France

    Vincent Roule

  4. Service de Pharmacologie, CHU de Caen Normandie, PICARO Cardio-Oncology Program, 14000, Caen, France

    Joachim Alexandre, Basile Chrétien, Marion Sassier, Sophie Fedrizzi & Charles Dolladille

  5. ACTION Study Group, Pitié-Salpêtrière University Hospital, Cardiology Department, Paris, France

    Farzin Beygui

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Contributions

VR and CD: Formal analysis, Writing—Original Draft; CD: statistical analysis and methodology; AL, BC, MS and SF: Writing – Review, Validation; FB and JA: Writing—Review & Editing, Supervision.

Corresponding author

Correspondence to Vincent Roule.

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Competing Interests

Dr Roule has received research grants from Medtronic; speaker fees from Bristol-Myers Squibb, AstraZeneca.

Dr Beygui reports receiving consulting and lecture from Astrazeneca, Bristol-myers Squibb, medtronic, biosensors, Boston scientific Institutionnal research grants: Medtronic, Biosensors, Acist, Boston scientific.

Other authors have nothing to report.

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Roule, V., Alexandre, J., Lemaitre, A. et al. Rhabdomyolysis with Co-Administration of Statins and Antiplatelet Therapies—Analysis of the WHO Pharmacovigilance Database. Cardiovasc Drugs Ther (2023). https://doi.org/10.1007/s10557-023-07459-8

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