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Meta-Analysis
. 2022 Oct 12;75(8):1416-1422.
doi: 10.1093/cid/ciac128.

Association Between Statin Use and Daptomycin-related Musculoskeletal Adverse Events: A Mixed Approach Combining a Meta-analysis and a Disproportionality Analysis

Masayuki Chuma  1   2 , Aki Nakamoto  3 , Takashi Bando  3 , Takahiro Niimura  3 , Yutaka Kondo  4 , Hirofumi Hamano  1   3 , Naoto Okada  3 , Mizuho Asada  5 , Yoshito Zamami  3   6   7 , Kenshi Takechi  1   8 , Mitsuhiro Goda  3   6 , Koji Miyata  6 , Kenta Yagi  1 , Toshihiko Yoshioka  3 , Yuki Izawa-Ishizawa  9 , Hiroaki Yanagawa  1 , Yoshikazu Tasaki  2 , Keisuke Ishizawa  3   6
Affiliations
Meta-Analysis

Association Between Statin Use and Daptomycin-related Musculoskeletal Adverse Events: A Mixed Approach Combining a Meta-analysis and a Disproportionality Analysis

Masayuki Chuma et al. Clin Infect Dis. .

Abstract

Background: There is a growing concern about the association between the combined use of daptomycin (DAP) and statins and the occurrence of musculoskeletal adverse events (MAEs), but this remains controversial. This study aimed to clarify the association between statin use and DAP-related MAEs.

Methods: We used a mixed approach that combines 2 methodologies. First, we conducted a meta-analysis to examine the effects of statin use on DAP-related MAEs. Second, we conducted a disproportionality analysis using the US Food and Drug Administration Adverse Events Reporting System (FAERS) to further confirm the results of the meta-analysis and to examine the effect of each type of statin on DAP-related MAEs in a large population.

Results: In the meta-analysis, statin use significantly increased the incidence of DAP-related rhabdomyolysis (odds ratio [OR]: 3.83; 95% confidence interval [CI]: 1.43-10.26) but not DAP-related myopathy (OR: 1.72; 95% CI: .95-3.12). In the disproportionality analysis using the FAERS, the use of statin significantly increased the reporting OR (ROR) for DAP-related myopathy (ROR: 5.69; 95% CI: 4.31-7.51) and rhabdomyolysis (ROR: 5.77; 95% CI: 4.33-7.68). Atorvastatin, rosuvastatin, and simvastatin all increased the incidence of DAP-related myopathy and rhabdomyolysis.

Conclusion: The mixed approach combining a meta-analysis and disproportionality analysis showed that statin use was associated with the occurrence of DAP-related rhabdomyolysis. The appropriate use of statins and DAP should be performed with careful consideration of its safety.

Keywords: daptomycin; disproportionality analysis; meta-analysis; musculoskeletal adverse event; statin.

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Conflict of interest statement

Potential conflicts of interest. Y. T. received speaker fees from Daiichi-Sankyo Co., Ltd. The other authors have no conflicts of interest to declare. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Flow diagram of the study design. FAERS, US Food and Drug Administration Adverse Events Reporting System; DAP, daptomycin; MAE, musculoskeletal adverse event.
Figure 2.
Figure 2.
Forest plot comparing the incidence of myopathy between DAP and DAP + statin groups. CI, confidence interval; DAP, daptomycin; OR, odds ratio.
Figure 3.
Figure 3.
Forest plot comparing the incidence of rhabdomyolysis between DAP and DAP + statin groups. CI, confidence interval; DAP, daptomycin; OR, odds ratio.
See this image and copyright information in PMC

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