Statins can regress coronary atheroma and lower clinical events. Although pre-clinical studies suggest procalcific effects of statins in vitro, it remains unclear if statins can modulate coronary atheroma calcification in vivo.
Objectives
This study compared changes in coronary atheroma volume and calcium indices (CaI) in patients receiving high-intensity statin therapy (HIST), low-intensity statin therapy (LIST), and no-statin therapy.
Methods
In a post-hoc patient-level analysis of 8 prospective randomized trials using serial coronary intravascular ultrasound, serial changes in coronary percent atheroma volume (PAV) and CaI were measured across matched coronary segments in patients with coronary artery disease.
Results
Following propensity-weighted adjustment for differences in baseline and changes in clinical, laboratory, and ultrasonic characteristics, HIST (n = 1,545) associated with PAV regression from baseline (−0.6 ± 0.1%; p < 0.001), whereas both LIST (n = 1,726) and no-statin therapy (n = 224) associated with PAV progression (+0.8 ± 0.1% and +1.0 ± 0.1%; p < 0.001, respectively; p < 0.001 for both HIST vs. LIST and HIST vs. no-statin; p = 0.35 for LIST vs. no-statin). Significant increases in CaI from baseline were noted across all groups (median [interquartile range] HIST, +0.044 [0.0–0.12]; LIST, +0.038 [0.0–0.11]; no-statin, +0.020 [0.0–0.10]; p < 0.001 for all), which could relate to statin intensity (p = 0.03 for LIST vs. no-statin; p = 0.007 for HIST vs. no-statin; p = 0.18 for HIST vs. LIST). No correlations were found between changes in CaI and on-treatment levels of atherogenic and antiatherogenic lipoproteins, and C-reactive protein, in either of the HIST groups or the no-statin group.
Conclusions
Independent of their plaque-regressive effects, statins promote coronary atheroma calcification. These findings provide insight as to how statins may stabilize plaque beyond their effects on plaque regression.
Key Words
atherosclerosis
calcium
intravascular ultrasound
statins
Abbreviations and Acronyms
CaI
calcium index
CRP
C-reactive protein
CT
computed tomography
HIST
high-intensity statin therapy
IVUS
intravascular ultrasound
LDL-C
low-density lipoprotein cholesterol
LIST
low-intensity statin therapy
PAV
percent atheroma volume
TAV
total atheroma volume
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Dr. Nissen has received research support from Amgen, AstraZeneca, Eli Lilly, Orexigen, Vivus, Novo Nordisk, Resverlogix, Novartis, Pfizer, Takeda, Sankyo, and Sanofi; and has served as a consultant for a number of pharmaceutical companies without financial compensation because all honoraria, consulting fees, or any other payments from any for-profit entity are paid directly to charity so that neither income nor any tax deduction is received. Dr. Nicholls has received research support from AstraZeneca, Novartis, Eli Lilly, Anthera, LipoScience, Roche, and Resverlogix; and received honoraria from or served as a consultant to AstraZeneca, Roche, Esperion, Abbott, Pfizer, Merck, Takeda, LipoScience, Omthera, Novo-Nordisk, Sanofi, Atheronova, Anthera, CSL Behring, and Boehringer Ingelheim. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
