The extent to which short-term intensified statin treatment may modulate plaque lipid
content, alter plaque structure, and change flow physiology as assessed by non-invasive
imaging remains unknown. Furthermore, no data is available regarding the effects of
short-term intensified statin therapy on coronary plaques as assessed by Photon-Counting
Detector CT (PCD-CT). In addition, no data is available regarding the long-term effects
of short, intensified statin therapy on plaque morphology (i.e., plaque memory).
Therefore, in this randomized, controlled, prospective, double-blind, single-center
clinical trial, we aimed 1) to assess the effect of short-term intensified statin therapy
on coronary anatomy and physiology using PCD-CT and 2) to assess the effect of short,
intensified statin treatment on long term changes in plaque characteristics. In other
words, to test our "plaque memory" hypothesis. Our analyses include a detailed evaluation
of plaques by combining anatomic (quantitative and qualitative plaque assessment,
radiomics) and hemodynamic (Fractional Flow Reserve-CT, FFR-CT) information.
In this randomized, controlled, prospective double-blinded single-center clinical trial,
we aim to enroll statin naive patients (patients with no previous or current statin
treatment) who underwent PCD-CT (NAEOTOM Alpha, Siemens Healthineers, Erlangen, Germany)
exam due to stable chest pain and suspected coronary artery disease (CAD) at the Medical
Imaging Centre of Semmelweis University, Budapest, Hungary. Coronary CT Angiography
(Coronary CTA) examinations will be performed in accordance with the current guidelines
of the Society of Cardiovascular Computed Tomography.
We will enroll patients aged 30-65 years, with at least one partially calcified or
non-calcified plaque and with negative FFR-CT (FFR-CT>0.75 distal to stenosis).
Patients with contraindications to coronary CTA and patients post-revascularisation will
be excluded from the study. Additional exclusion criteria: patients receiving
lipid-lowering therapy before coronary CTA exam; alanine aminotransferase (ALT) levels
>3× upper limit of normal (ULN); unexplained serum creatine kinase (CK) level >3× ULN;
serum creatinine >2 mg/dL (177 umol/l), elevated low-density lipoprotein (LDL) level >5
mmol/L.
Patients will be randomized into 'high-dose statin' and 'placebo' groups, considering the
age and sex of the patients to achieve equal representation of age groups and genders in
both arms. Based on the sample size calculation, 70-70 patients must be randomized into
each group. For those who will be randomized to the 'high-dose statin' group, 40 mg
rosuvastatin therapy will be initiated. For those who will be randomized to the 'placebo'
group, a placebo therapy will be started with medications that look the same as 40 mg
rosuvastatin pills.
All the included patients will undergo repeated coronary CTA at 3 months and 24 months
after the baseline CT. After the 3-month coronary CTA control, rosuvastatin dose per
standard of care will be initiated. The 3-month and 24-month control coronary CTA
evaluations will be the same as the baseline CT scans. All coronary CTA exams will be
performed using a low radiation dose protocol utilizing the advanced imaging capabilities
of PCD-CT.
All the included patients will undergo repeated coronary CTA at 3 months and 24 months
after the baseline CT with a standardized acquisition protocol.
Proposed scan parameters for all patients are as follows: tube voltage = 120 kVp (due to
improved spectral data), automatic tube current modulation with image quality level
(IQ-level) = 80, detector configuration = 144 mm × 0.4 mm, rotation time = 0.25 s. All
coronary CTA exams will be performed by using a low radiation dose protocol utilizing the
advanced imaging capabilities of PCD-CT.
Patients may receive intravenous or oral beta blockers if their heart rate (HR) is > 65
beats/minute before the examination. All patients will receive a nitroglycerine
transdermal patch before CTA scanning if systolic blood pressure is > 100 Hgmm.
Prospectively triggered acquisition mode is preferred in case of regular HR > 70
beats/min, and helical scan mode if HR is irregular. Images will be acquired in diastole
(65-85% of the R-R interval) or systole (200-400 ms), depending on the HR (< or > 75
beats/minute). A four-phasic contrast injection protocol with 70-80 mL contrast agent at
a flow rate of 4.5-5.0 mL/s is recommended.
Special attention will be given to ensure that the baseline CT scan parameters are
consistent with the follow-up scans for each patient. Images and coronary segments with
severe motion, breathing, beam-hardening, or misalignment artifacts will be excluded from
the analysis. Coronary segments matched to the segment with artifacts will also be
excluded in all scans.
The primary endpoint will be evaluated at 3 months, while "plaque memory" will be
assessed at 24 months of follow-up.
