Journal Presentation

Presentan : Erika
Pembimbing : dr. Nur Yasmin K, SpPD, SpJP
 BACK GROUND
The burden and composition
Important diagnostic and Statin reduces circulating lipid
atherosclerotic coronary
prognostic information levels and cardiovascular events
plaques

Serial intracoronary imaging

Favourable morphological changes  significant regression of total
studies assessing the effect of
plaque volume (TPV) and lipid composition
statin on coronary plaques

CCTA ;
• A clinically established imaging method that allows for non invasive identification of coronary artery atherosclerosis
and reliable characterization and quantification of coronary plaque
• Allows accurate description of non-calcified plaque (NCP) types including adverse plaque characteristics (APC), low
attenuation plaques (LAP), spotty calcified plaques, and positive remodelling
 BACK GROUND
The ability of CCTA in differentiation of plaque tissue characteristics has been shown to be comparable to intravascular
ultrasound (IVUS) and optical coherence tomography (OCT)

The non-invasive nature and wide availability of CCTA makes it an attractive method to investigate serial morphological
plaque changes.

Studies using CCTA to assess the effect of statin therapy on plaque remodeling  important and additive information 
risk stratification and decision-making  appropriate therapeutic choice in patient with CAD with or without APC

This study performed a systematic literature review and meta-analysis on the potential role of CCTA in assessing the
remodelling impact of statin therapy on coronary plaque burden and composition
 AIM
To clarify the potential role of coronary computed tomographic angiography (CCTA) in
assessing the remodeling impact of statin therapy on plaque burden and compositions
 METHODS

DESIGN  A systematic review and meta-analysis

according to the Preferred Reporting Items for systematic review and Meta-analysis (PRISMA)

SEARCH STRATEGY :
• The search was conducted in the electronic databases PubMed, EMBASE, and Cochrane library for all
published studies that examined the effect of statins on coronary plaque composition using CCTA
• The following keywords in different combinations, were used: computed tomography (CT), angiography,
coronary, plaque, and statin
• The literature search was restricted to published studies after year 2000 (after introduction of the multi-
slice CT technique) and up to 1 May 2017
 METHODS
STUDY ELIGIBILITY  RCT or observational studies reporting the effect of statin therapy alone on coronary
plaque burden and or composition at baseline or follow up period  were eligible for
inclusion

The following parameters defined by the

studies were considered eligible:  Intensive statin treatment : achievement of
• TPV substantial reduction of low density lipids
(LDL) with a target level of 70 or 80mg/dL
• NCP volume either by increasing the statin dose or
• LAP volume [defined as Hounsfield unit administration of a maximal statin dose
(HU) <30] or lipid core volume,  The moderate (usual care) dose receivers
• Calcified plaque volume, continued their usual dose without a minimum
target level of LDL.
• Plaque signal density measured as HU

All analyses were performed using the meta-analysis package of the statistic software program STATA version
13 (STATA Corporation, Lakeway Drive, College Station, TX, USA)
RESULT
 2 studies RCT
 5  non randomized observational studies with controls
 5  observational studies without controls

The risk profile of patients Intensive, moderate and control

group :

• Age : mean age of 61.5± 7.2, 61.1± 7.5, and 60.5± 7.2 yo
• Gender : 71%, 71% & 74% male gender
• Risk factors :
• Hypertension 58%, 58%, and 51%
• Dyslipidemia 57%, 49% and 47%
• Diabetes 35%, 21%, and 27%
• Current smoking 42%, 25%, and 36%
Differences between the three groups  no statistically
significant
 IMAGE ACQUISITION AND PLAQUE ASSESMENT
• CCTA images were acquired using different CT equipment
• Software for 3D plaque analysis
• All studies  images or coronary segments of poor quality due to
artefacts were excluded
• Using semi-automated or automated software for plaque analysis was
reported in six studies.
• All readers were blinded to clinical data in nine studies, but this was
unclear in three studies
The Effect of Statin Therapy on TPV
• Meta-analysis 10 studies  TPV decreased
significantly P<0.001 (intensive VS control)
• Moderate VS control  decreased TPV not
significant
• % of mean volume regression was -3.6% and
-0.4% in intensive and moderate statin
receivers, respectively, vs +5.7% progression in
controls
• Analysis of mean differences (six studies) 
magnitude of TPV decreased in statin therapy
receivers regardless of dose intensity compared
with controls was -30.4 (95% CI -41.6, -19.1; P<
0.001)mm3
 The effect of statin therapy on NCP volume

• Meta-analysis (3 studies)  NCP volume decreased in patients receiving statin therapy and increased in control (not
statistically significant, -7.62 (95% CI -17.38, 2.13; P= 0.124) vs. 12.04 (95% CI -1.78, 25.86; P= 0.088) mm3
• % of mean volume regression : -9% in intensive statin therapy receivers vs. a progression of +12% in controls.
• Analysis of mean differences between statin and control arms showed a significant plaque volume regression
of -0.99 (95% CI -1.35, -0.62; P< 0.001) mm3 in patients receiving statin therapy.
 The effect of statin therapy on LAP volume

• Meta-analysis of data from (5 studies)  mean LAP volume decreased significantly in patients receiving statin therapy by -5.84 (95%
CI -8.02, -3.66; P< 0.001) mm3 vs. an insignificant increase by 1.36 (95% CI -0.75, 3.46; P= 0.207) mm3 in controls
• % of mean volume regression in statin-receiving patients  -15.8% vs.þ6.3% progression in controls
• Meta-analysis of the mean differences between statin and control groups showed a significant LAP volume reduction in favour of
statin therapy receiving patients -0.52 (95% CI -0.74, -0.31; P< 0.001)mm3.
The effect of statin therapy on calcified plaque volume and density

• Meta-analysis (4 studies)  calcified plaque volume increased significantly in patients receiving

statin but not significantly in controls
• % mean volume progression was +12.0% in patients receiving statin therapy vs. +3.5% in controls
• Metaanalysis of mean differences in statin receivers vs. controls (2 studies) no significant difference in calcified volume plaque
progression with a difference of 4.1
• Meta-analysis (4 studies) assessing changes in calcium density signal after statin therapy showed a significant increase 21.99 (95% CI
9.2, 34.8; P< 0.001) HU
 Changes in total and LDL cholesterol
• Total cholesterol and LDL declined (statin group) from 207± 14 and
125± 17 at baseline to 153± 24 and 74.5± 16mg/dL at follow-up
• Estimated weighted mean differences of -62.4 (-64.8, -60.1) and -65.1
(-67.1, -63.1) mg/L, respectively (both P< 0.001)
• In intensive statin arms, a target level of LDL below 80mg/dL was
achieved.
Comparison of plaque changes w/ the previously published IVUS & OCT studies
Discussion
• This systematic review and meta-analysis  an updated overview of
the published studies assessing the impact of statin therapy on different
coronary plaque volumes and composition determined by CCTA
• Intensive statin therapy was associated with regression in TPV and LAP
volume
• Moderate statin therapy was not followed by significant changes in TPV
• Statin therapy was associated with increase in calcified plaque volume
and calcium signal intensity as well
Discussion
• On contrary, no statin therapy  progression in TPV and LAP volume
without any significant increase in calcified plaque volume
• These volumetric and compositional plaque changes associated with a
substantial fall in total cholesterol and LDL levels supported a causal
and plaque stabilizing effect of statin therapy
• The result of this study in agreement with previous studies using IVUS
(significant reduction TPV during an 18 mo)
• IVUS studies  no reduction in LAP volume
Discussion
• OCT studies have demonstrated a significant increase in fibrous cap
thickness (FCT) at expense of a decrease in LAP volume after statin
therapy
• Volume reduction of LAP assessed with CCTA and OCT, but not with
IVUS may
• These findings may further suggest that plaque remodelling is a
complicated process that may favourably be assessed by an integrated
multi-modality imaging approach.
Discussion
• The mechanism explaining the beneficial changes of statin therapy on
plaque morphology and, ultimately, improved cardiovascular outcome 
most likely due to its LDL-lowering effect
• Recent large-scale randomized trials with novel LDL-lowering therapies
have shown relative risk reductions per mmol/L fall in LDL comparable to
that of statin therapy.
• Adding a PCSK9-inhibitor to statin therapy has shown to reduce both LDL
and TPV beyond that achieved by statins alone.
• However, large-scale prognostic trials using appropriate plaque imaging
modalities including CCTA are warranted to better clarify the mechanisms
responsible for the compositional plaque changes accompanied by lipid-
lowering therapies.
Discussion
• The mechanism explaining the beneficial changes of statin therapy on
plaque morphology and, ultimately, improved cardiovascular outcome 
most likely due to its LDL-lowering effect
• Recent large-scale randomized trials with novel LDL-lowering therapies
have shown relative risk reductions per mmol/L fall in LDL comparable to
that of statin therapy.
• Adding a PCSK9-inhibitor to statin therapy has shown to reduce both LDL
and TPV beyond that achieved by statins alone.
• However, large-scale prognostic trials using appropriate plaque imaging
modalities including CCTA are warranted to better clarify the mechanisms
responsible for the compositional plaque changes accompanied by lipid-
lowering therapies.
 LIMITATION
• The studies included in this review  small sizes and most of them were
of observational nature
• Characterized by substantial heterogeneity concerning baseline
populations, study design, types of statins used, and length of follow-up
period.
• In some studies, it was unclear whether the readers were blinded to
clinical data or inter-observer evaluation was performed.
• The included studies did not directly compare CCTA plaque evaluation vs.
a reference method. Therefore, the results of this study should be
interpreted cautiously.
 CONCLUSION
• Initial studies demonstrated the potential role of CCTA in evaluating the
effect of statin therapy on plaque volume and composition.
• The possible plaque stabilizing effect of statins seems dose-related.
• Future trials implicating advanced CCTA technologies with higher
resolution are required to explain further mechanisms behind
compositional plaque changes following use of anti-atherosclerotic
therapies.
THANK YOU