Efficacy and Safety of Alternate-Day Versus Daily Dosing of Statins: a Systematic Review and Meta-Analysis
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.
- 7.Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013; doi: 10.1002/14651858.CD004816.pub5.
- 11.Mabuchi H, Kita T, Matsuzaki M, Matsuzawa Y, Nakaya N, Oikawa S, et al. Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia and coronary heart disease. Circ J. 2002;66:1096–100.CrossRefPubMedGoogle Scholar
- 14.Pyörälä K, Ballantyne CM, Gumbiner B, Lee MW, Shah A, Davies MJ, et al. Reduction of cardiovascular events by simvastatin in nondiabetic coronary heart disease patients with and without the metabolic syndrome: subgroup analyses of the scandinavian simvastatin survival study (4S). Diabetes Care. 2004;27:1735–40.CrossRefPubMedGoogle Scholar
- 23.Mikhailidis DP, Katsiki N, Athyros VG. Adherence to statin treatment: an important issue in clinical practice. Curr Med Res Opin. 2016:1–2.Google Scholar
- 31.Colantonio LD, Huang L, Monda KL, Bittner V, Serban M-C, Taylor B, et al. Adherence to high-intensity statins following a myocardial infarction hospitalization among medicare beneficiaries. JAMA Cardiol. 2017;16:1886–97.Google Scholar
- 35.Keleş T, Akar Bayram N, Kayhan T, Canbay A, Sahin D, Durmaz T, et al. The comparison of the effects of standard 20 mg atorvastatin daily and 20 mg atorvastatin every other day on serum LDL-cholesterol and high sensitive C-reactive protein levels. Anadolu Kardiyol Derg. 2008;8:407–12.PubMedGoogle Scholar
- 38.Balk EM, Earley A, Patel K, Trikalinos TA, Dahabreh IJ. Empirical assessment of within-arm correlation imputation in trials of continuous outcomes. Agency for Healthcare Research and Quality (US); 2012. Report No.: 12(13)-EHC141-EF.Google Scholar
- 40.Methods guide for effectiveness and comparative effectiveness reviews. Agency for Healthcare Research and Quality (US); 2008. PMID: 21433403.Google Scholar
- 45.Aghasadeghi K, Zare D. Efficacy of alternate day dosing of atorvastatin. Cent Eur J Med. 2008;3:163–6.Google Scholar