Impact of rosuvastatin versus atorvastatin on coronary atherosclerotic plaque volume – a systematic review and meta-analysis with trial sequential analysis of randomized control trials

Abstract

The role of statin therapy in secondary prevention of ischemic heart disease is well established by large randomized controlled trials (RCTs). Statin therapy is strongly recommended by American College of Cardiology/American Heart Association (AHA) guidelines for secondary prevention with a high level of evidence. Currently, the role of statins in patients with intermediate-risk cardiovascular disease is being explored with promising results. Therapeutic equivalent doses of statins were analyzed in a meta-analysis reporting statistically significant difference in cholesterol lowering effect, but of little therapeutic importance because of the small difference in low-density lipoprotein cholesterol (LDL-C). However, large RCTs with therapeutically equivalent doses of statins have showed varied effect on the progression of coronary atherosclerosis. Furthermore, studies have also reported the association between plaque regression as assessed by intravascular ultrasound and its interrelation with lower rates of cardiovascular events. The need for intensification of statin therapy for secondary prevention and its effect on atheroma volume has also been outlined recently, without specifics on the type of statin utilized. Several studies have compared the effect of rosuvastatin versus atorvastatin on regression of coronary atherosclerotic plaque and stability. Hence we performed an updated meta-analysis with trial sequential analysis comparing the effect of rosuvastatin versus atorvastatin on coronary atherosclerotic plaque regression. The meta-analysis was performed in accordance with the PRISMA (preferred reporting items for systemic review) and AHA guidelines. Medline/PubMed and Cochrane database were used to search relevant articles from inception to 18 April 2019. We also manually searched bibliographies of studies and reviews to include studies not identified from the search. Relevance of the articles was assessed by two independent reviewers (AK and MS) based on the predefined inclusion criteria. Any discrepancies were solved by consultation with the senior author (RD). Articles were eligible for inclusion if the following criteria were met: 1) RCTs published in any language from inception to day of article search with no limit in sample size. 2) Comparing rosuvastatin with atorvastatin in therapeutic equivalent doses (rosuvastatin versus atorvastatin dose in the ratio 1:2). 3) Reporting percentage change in atheroma volume (PAV), which would be considered the primary outcome of interest. The other outcomes that were considered include: a) change in total atheroma volume. Information was also extorted from the included articles relating to: i) change in LDL-C and ii) change in high-density lipoprotein cholesterol (HDL-C). Results from the studies will be presented as mean and standard deviation. Two authors (AK and MS) independently extracted data from each included article using a standardized data extraction form. The quality of the included studies were assessed using the Cochrane risk of bias version 1 form. The analysis was carried out using RevMan Version 5.3. (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). We used inverse variance method with random effect model to calculate mean difference with 95% confidence interval. Forest plots were generated to visually assess the result of pooling. We used I measures to determine heterogeneity. Publication bias was assessed with the help of