Efficacy of Alternate Day Statins for Lipid Reduction: A Systematic Review and Meta-Analysis
Abstract
BACKGROUND: Statins have proven to be beneficial in reducing cardiovascular morbidity and mortality. The data indicates that stains are underutilized due to cost considerations and unpleasant side effects. To overcome this problem, alternate day regimens of statins were proposed. The primary objective of this meta-analysis was to determine if alternate day dosing is as effective as daily dosing in blood lipid levels.
METHODOLOGY: Literature search was conducted using Medline, Embase, Cochrane Central Register of Controlled Clinical Trials, and Cochrane Database of Systematic Review (CDSR). Randomized controlled trials that measured reduction in blood levels in adult patients with hyperlipidemia via alternate day statin strategy use were included. The primary outcome was reduction in serum LDL concentration while the secondary outcomes were triglyceride (TG) and total cholesterol (TC) reduction. Meta-analysis was done using random effects model utilizing DerSemonian and Laird method. Quality assessment was done using Cochrane Collaboration’s tool. Heterogeneity was assessed using Q-statistic and quantified with I2. Publication bias was assessed with a funnel plot.
RESULTS: A total of 315 studies were screened and 16 studies were included in the final analysis. Group 1 was designated as “Dose Independent group” meaning that the daily dose and the alternate day dose was the same, and thus the total weekly dosing was half in the alternate day group. Group 2 was the “Dose Equivalent group” implying that the alternate day dose was more than the daily dose, such that the total weekly dose was the same. The comparison of daily to alternate day regiments in Group 1 showed greater LDL reduction (μ reduc- tion=7.44; CI 0.99 to 13.88; p=0.02; I2=59%) and TC (μ reduction=6.85; CI 0.15 to 13.55; p=0.05; I2=63%) with daily use, and equivalent TG (μ reduction=0.42; CI -7.71 to 8.55; p=0.02; I2=0%) reduction in both regiments. Group 2 showed no difference between the regiments in LDL reduction (μ reduction=-4.25; CI -23.32 to 14.83; p=0.66; I2=90.2%) and TC reduction (μ reduction=-2.32; CI -20.113 to 15.47; p=0.8; I2=85.6%).
CONCLUSION: Our results show that the daily regimen is marginally favorable over alternate day dose if the statin is unchanged (the total weekly dosing is halved in the alternate day group). If the alternate day dose is increased so that the total weekly dose of the statin is the same as the daily regimen, the LDL and TC reductions are comparable. Hence alternative day statin therapy may be a reasonable treatment option in patients with side effects and compliance issues. Our analysis is be limited by the high heterogeneity, missing data points and lack of individual patient data.