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Efficacy and Safety of Alternate-Day Versus Daily Dosing of Statins: a Systematic Review and Meta-Analysis

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Abstract

Purpose

We conducted a meta-analysis of randomized controlled trials (RCTs) and quasi-RCTs to synthesize evidence about the efficacy and safety of alternate-day vs daily dosing of statins.

Methods

We searched selected databases through January 2, 2017 to identify relevant RCTs and quasi-RCTs. The primary outcome was change in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG), while secondary outcomes included adverse events and adherence.

Results

Twelve RCTs and 1 quasi-RCT (n = 1023 patients) were included in the analysis. Pooled analysis revealed no statistically significant difference between alternate-day and daily regimens of atorvastatin and rosuvastatin in terms of change in LDL-C (mean difference [MD] 6.79 mg/dL, 95% confidence interval [CI] −1.59, 15.17, p = 0.11, and 10.51 mg/dL, 95%CI −0.23, 21.26, p = 0.06, respectively) and TG (p > 0.05). Daily regimens of atorvastatin and rosuvastatin were superior to alternate-day regimes in term of change in TC (MD 12.45 mg/L, 95%CI 8.14, 16.76, p < 0.00001, and 15.80 mg/dL, 95%CI 5.66, 25.95, p = 0.002, respectively). For all outcomes, there was no statistically significant difference between alternate-day and daily regimens for both fluvastatin and pravastatin (p > 0.05). Both regimens of statins were generally well tolerated with good adherence.

Conclusions

Alternate-day dosing of individual statins (especially atorvastatin and rosuvastatin) is as efficacious as daily dosing on LDL-C and TG.

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Acknowledgements

We thank Stephen A LaHaye (MD, FRCPC) and Andrew G Day (MSc) for providing data from their trial [32].

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Authors and Affiliations

  1. Faculty of Medicine, Zagazig University, El-Sharkia, Zagazig, 44519, Egypt

    Kamal Awad

  2. Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK

    Dimitri P. Mikhailidis

  3. Preventive Cardiology, CGH Medical Center, Sterling, IL, USA

    Peter P. Toth

  4. The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA

    Peter P. Toth & Steven R. Jones

  5. Division of Clinical Pharmacology, University of Kansas Medical Center, Kansas City, KS, USA

    Patrick Moriarty

  6. Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA

    Patrick Moriarty

  7. University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, UK

    Gregory Y. H. Lip

  8. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA

    Paul Muntner

  9. Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy

    Alberico L. Catapano

  10. IRCCS Multimedica, Milan, Italy

    Alberico L. Catapano

  11. Department of Biostatistics and Bioinformatics, Duke Clinical Research Institute, Chapel Hill, NC, USA

    Michael J. Pencina

  12. Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Robert S. Rosenson

  13. Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz (MUL), Lodz, Poland

    Jacek Rysz & Maciej Banach

  14. Polish Mother’s Memorial Hospital Research Institute, Lodz, Poland

    Maciej Banach

  15. Cardiovascular Research Centre, University in Zielona Gora, Zielona Gora, Poland

    Maciej Banach

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  1. Kamal Awad
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  2. Dimitri P. Mikhailidis
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on behalf of the Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group

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Correspondence to Kamal Awad.

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Conflict of Interest

Dimitri P. Mikhailidis has given talks and attended conferences sponsored by MSD, AstraZeneca and Libytec; Peter P. Toth consults for Abbvie, Amarin, AstraZeneca, Amgen, Gemphire, Kowa, Merck, Regeneron, and Sanofi and serves on the Speakers Bureau for Amarin, Amgen, Kowa, Merck, Regeneron, and Sanofi; Patrick Moriarty has research funding from Regeneron, Sanofi-Aventis, Pfizer, Novartis, Amgen, Ionis, and Catabasis, and he serves as a consultant for Genzyme, Kowa, Duke Clinical Research Institute, Eliaz Therapeutics, Aegerion, Alexion, and Esperion; Paul Muntner received grant support and honoraria from Amgen; Alberico L. Catapano has received research grants to his institution from Amgen, Astra-Zeneca, Merck, Regeneron/Sanofi, and Sigma Tau and honoraria for lectures, advisory boards, or as a steering committee member from Aegerion, Akcea, Amgen, Sanofi-Regeneron, Pfizer, AstraZeneca, ISIS Pharma, Kowa, Lilly, Boehringer Ingelheim, MSD,Sigma Tau, Recordati; Michael J. Pencina declares research grants from Sanofi-Regeneron; Robert S. Rosenson declares research funding to his institution from Akcea, Amgen, Astra Zeneca, Eli Lilly, Esperion, Medicines Company, Regneron, and Sanofi; advisory board fees from Akcea, Amgen, Easy Vitals, Eli Lilly, Regneron and Sanofi; honoraria from Kowa; royalties from UpToDate, Inc.; and stock holdings in MediMergent LLC; Maciej Banach declares advisory boards fees from Abbott Vascular, Amgen, Daichi Sankyo, Esperion, Lilly, MSD, Resverlogix, Sanofi-Aventis, Speakers Bureau from Abbott/Mylan, Abbott Vascular, Actavis, Akcea, Amgen, Biofarm, KRKA, MSD, Sanofi-Aventis, and Valeant and grants from Valeant, Sanofi-Aventis.

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Awad, K., Mikhailidis, D.P., Toth, P.P. et al. Efficacy and Safety of Alternate-Day Versus Daily Dosing of Statins: a Systematic Review and Meta-Analysis. Cardiovasc Drugs Ther 31, 419–431 (2017). https://doi.org/10.1007/s10557-017-6743-0

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