Efficacy and Safety of Alternate-Day Versus Daily Dosing of Statins: a Systematic Review and Meta-Analysis
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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.
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.
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.
Alternate-day dosing of individual statins (especially atorvastatin and rosuvastatin) is as efficacious as daily dosing on LDL-C and TG.
KeywordsCholesterol LDL cholesterol Lipids Lipoproteins Statins
We thank Stephen A LaHaye (MD, FRCPC) and Andrew G Day (MSc) for providing data from their trial .
Compliance with Ethical Standards
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.
This article does not include any studies with human participants or animals performed by any of the authors.
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