|Meta-analysis of the studies assessing temporal changes in coronary plaque volume using intravascular ultrasound
|Rodriguez-Granillo G A, Agostoni P, Garcia-Garcia H M, Biondi-Zoccai G G, Mc Fadden E, Amoroso G, de Jaegere P, Bruining N, de Feyter P, Serruys P W
This review concluded that statins appear to promote a regression of coronary plaque volume, as measured by intravascular ultrasound, when achieving a target low-density lipoprotein cholesterol level. However, the findings of the review should be interpreted with caution and may not be reliable, given their
reliance on indirect comparisons, the lack of any assessment of study quality, and the significant variability between the studies.
To determine the effectiveness of statin therapy on coronary atherosclerotic plaque volume over time by intravascular ultrasound (IVUS).
PubMed was searched without language restrictions for peer-reviewed journal articles published between January 1990 and January 2006; the search terms were reported. References were also checked and experts in the area contacted.
Study designs of evaluations included in the review
The authors did not specify which types of study design were eligible for inclusion. Randomised placebo-controlled trials and one single-arm observational study were included in the review.
Specific interventions included in the review
Studies in which at least one treatment group received statin therapy were eligible for inclusion. Statin treatment included atorvastatin, pravastatin and simvastatin. The length of follow-up ranged from 6 to 18 months.
Participants included in the review
The authors did not specify which types of participants were eligible for inclusion. The mean age of the participants included in the studies ranged from 56 to 67 years. The majority of the participants in each study were male (range: 71 to 100%).
Outcomes assessed in the review
The primary outcome was progression or regression of coronary atherosclerotic burden in native coronary arteries evaluated by IVUS. Studies with no volumetric output (only cross-sectional area analysis), or those in which the measurement was taken from vessels other than coronary arteries, were excluded.
How were decisions on the relevance of primary studies made?
Two reviewers independently screened potentially relevant articles for inclusion in the review.
Assessment of study quality
The authors did not state that they assessed validity.
Data were extracted onto pre-specified forms and the original study authors were contacted for missing data if necessary. The authors did not state how many reviewers were involved in the data extraction.
Methods of synthesis
How were the studies combined?
The studies were combined in a meta-analysis using a random-effects model. Summary effect sizes were presented as weighted mean differences (WMDs) with their corresponding 95% confidence intervals (CIs). Publication bias was assessed using a funnel plot.
How were differences between studies investigated?
Statistical heterogeneity was assessed using the Cochran Q test. Sensitivity analyses were performed: studies were stratified according to low-density lipoprotein (LDL) cholesterol levels and time to follow-up.
Results of the review
Nine studies (n=985, 11 statin treatment arms) were included in the review.
After a mean follow-up of 9.8 months, a significant decrease in plaque volume was found (WMD -5.77 mm3, 95% CI: -10.36, -1.17); there was no evidence of significant statistical heterogeneity. Stratification by a level of LDL cholesterol of less than 100mg/dL did not substantially alter this trend (WMD -7.88 mm3, 95% CI: -16.31, 0.55): there was no evidence of statistical heterogeneity. An LDL cholesterol level of 100 mg/dL or greater did not significantly decrease plaque volume (WMD -4.22 mm3, 95% CI: -10.27, 1.82); there was no evidence of statistical heterogeneity. No significant change in plaque volume was found in patients not treated with statins (WMD 0.13 mm3, 95% CI: -4.42, 4.68); no evidence of statistical heterogeneity was found. No evidence of publication bias was shown in the funnel plot.
Statin therapy appears to promote a significant regression of coronary plaque volume, as measured by IVUS, particularly when achieving a target LDL level.
The review question was supported by clear inclusion criteria relating to the intervention and outcomes; the authors did not specify the types of study design or participants. Only one database was searched and only articles published in peer-reviewed journals were included, which may mean that relevant studies have been missed. However, the search was not restricted by language. Although the authors assessed the possibility of publication bias, the test is unlikely to be reliable given the small number of studies included. The methodology undertaken to select papers was likely to have minimised reviewer error and bias. However, since it was not clear how the data were extracted, it is therefore not possible
to assess whether error or bias could have been introduced at this stage. The quality of the included studies does not appear to have been assessed, which makes it difficult to assess the reliability of the results.
The analyses assessed statistical heterogeneity and sensitivity analyses were performed to investigate the potential effects of study differences. Substantial heterogeneity was, however, evident between studies, as the authors acknowledged. The authors also highlighted that only one vessel was assessed with IVUS, thus it might not be representative of the total coronary atherosclerotic burden. The results of this review appear to indicate a regression of coronary plaque volume with statin therapy, as measured by IVUS, particularly in patients with an LDL level less than 100 mg/dL. However, these findings rely on
indirect comparisons which may not be reliable; no direct comparisons with patients not treated with statins were conducted, despite the majority of included studies directly comparing these groups of patients in randomised controlled trials. Overall, given the reliance on indirect comparisons, the
lack of any assessment of study quality, and the significant heterogeneity between studies, the findings of the review should be interpreted with caution and may not be reliable.
Implications of the review for practice and research
Practice: The authors did not state any implications for practice.
Research: The authors stated that it is important to establish standards regarding the acquisition, analysis and reporting of studies of IVUS.
Rodriguez-Granillo G A, Agostoni P, Garcia-Garcia H M, Biondi-Zoccai G G, Mc Fadden E, Amoroso G, de Jaegere P, Bruining N, de Feyter P, Serruys P W. Meta-analysis of the studies assessing temporal changes in coronary plaque volume using intravascular ultrasound. American Journal of Cardiology 2007; 99(1): 5-10
Subject indexing assigned by NLM
Cholesterol, LDL /blood; Coronary Artery Disease /blood /drug therapy /pathology /ultrasonography; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors /therapeutic use; Randomized Controlled Trials as Topic; Severity of Illness Index; Ultrasonography, Interventional
Database entry date
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.