Cardiovascular Drugs and Therapy

, Volume 31, Issue 4, pp 419–431 | Cite as

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

  • Kamal Awad
  • Dimitri P. Mikhailidis
  • Peter P. Toth
  • Steven R. Jones
  • Patrick Moriarty
  • Gregory Y. H. Lip
  • Paul Muntner
  • Alberico L. Catapano
  • Michael J. Pencina
  • Robert S. Rosenson
  • Jacek Rysz
  • Maciej Banach
  • on behalf of the Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group
REVIEW ARTICLE

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.

Keywords

Cholesterol LDL cholesterol Lipids Lipoproteins Statins 

Notes

Acknowledgements

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

Compliance with Ethical Standards

Funding

None to declare.

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.

Ethical Approval

This article does not include any studies with human participants or animals performed by any of the authors.

Informed Consent

Not applicable.

Supplementary material

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Fig. S6 (DOCX 15 kb)
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Table S1 (DOCX 15 kb)
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Table S2 (DOCX 20 kb)

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Kamal Awad
    • 1
  • Dimitri P. Mikhailidis
    • 2
  • Peter P. Toth
    • 3
    • 4
  • Steven R. Jones
    • 4
  • Patrick Moriarty
    • 5
    • 6
  • Gregory Y. H. Lip
    • 7
  • Paul Muntner
    • 8
  • Alberico L. Catapano
    • 9
    • 10
  • Michael J. Pencina
    • 11
  • Robert S. Rosenson
    • 12
  • Jacek Rysz
    • 13
  • Maciej Banach
    • 13
    • 14
    • 15
  • on behalf of the Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group
  1. 1.Faculty of MedicineZagazig UniversityZagazigEgypt
  2. 2.Department of Clinical Biochemistry, Royal Free Campus, University College London Medical SchoolUniversity College London (UCL)LondonUK
  3. 3.Preventive CardiologyCGH Medical CenterSterlingUSA
  4. 4.The Johns Hopkins Ciccarone Center for the Prevention of Heart DiseaseBaltimoreUSA
  5. 5.Division of Clinical PharmacologyUniversity of Kansas Medical CenterKansas CityUSA
  6. 6.Department of Internal MedicineUniversity of Kansas Medical CenterKansas CityUSA
  7. 7.University of Birmingham Institute of Cardiovascular Sciences, City HospitalBirminghamUK
  8. 8.Department of EpidemiologyUniversity of Alabama at BirminghamBirminghamUSA
  9. 9.Department of Pharmacological and Biomolecular SciencesUniversity of MilanMilanItaly
  10. 10.IRCCS MultimedicaMilanItaly
  11. 11.Department of Biostatistics and BioinformaticsDuke Clinical Research InstituteChapel HillUSA
  12. 12.Cardiovascular InstituteIcahn School of Medicine at Mount SinaiNew YorkUSA
  13. 13.Department of Hypertension, WAM University Hospital in LodzMedical University of Lodz (MUL)LodzPoland
  14. 14.Polish Mother’s Memorial Hospital Research InstituteLodzPoland
  15. 15.Cardiovascular Research CentreUniversity in Zielona GoraZielona GoraPoland

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