. 2024 Jan 30;25(2):51. doi: 10.31083/j.rcm2502051

Table 1.

A summary of clinical studies investigating the impact of statins on vascular calcification indices.

Reference	Participants; vascular calcification indices	Study design	Findings
Coronary artery disease
Schmermund A et al. (2006) [115]	471 pts w/o CAD, w/ $\geq$ 2 CV risk factors, CAC score $\geq$ 30;	• RCT: Group A (N = 235): ATORVA 80 mg; Group B (N = 236): ATORVA 10 mg	Group A vs group B:
	EBT: CAC	• Duration: 12 mo	↔ CAC
Kovarnik T et al. (2012) [132]	89 pts w/ stable angina;	• RCT: Group A (N = 18): Aggressive therapy ATORVA 80 mg/d + EZET 10 mg/d; Group S (N = 71): standard statin therapy (started by GP or ATORVA 10 mg/d statin-naive patients)	Group A vs group S:
	Coronary VH-IVUS	• Duration: 12 mo	↑ coronary dense calcification
Henein MY et al. (2011) [133]	11 studies, 1839 pts;	• Meta-analysis	High dose vs low-dose vs placebo:
	6 trials assessing CAC and 5 trials assessing coronary stenoses;	• High dose statins vs low dose statins vs placebo	↔ coronary calcification
	EBT, MDCT: CAC	• Duration: 12–24 mo	↓ coronary stenosis
Henein M et al. (2015) [124]	2 clinical trials w/ 1194 pts: St. Francis Heart Study (SFHS) and EBEAT Study;	• Pooled analysis of 2 RCTs	↑ CAC w/ greater statin doses and prolonged therapy
	CCTA: CAC score	• SFHS study — group A (N = 432): ATORVA 20 mg/d; group B (N = 419): placebo
		• EBEAT Study — group A (N = 179): ATORVA 80 mg/d; group B (N = 164): ATORVA 10 mg/d
		• Duration: CAC score at baseline, 2 y, 4–6 y in SFHS study and 0 and 12 mo in EBEAT study
Banach M et al. (2015) [122]	9 prospective clinical studies, 830 pts, 16 statin treatment arms;	• Systematic review & meta-analysis	All statins:
	coronary VH-IVUS	• Statin intervention: 737 pts (ATORVA, 10 to 80 mg/day; PRAVA, 10 to 40 mg/day; SIMVA, 20 mg/day; ROSUVA, 10 to 40 mg/day; FLUVA, 60 mg/day; PITAVA, 2 to 4 mg/day)	↑ coronary dense calcium volume
		• Placebo: 93 pts
Puri R et al. (2015) [126]	8 RCTs, 3495 participants;	• post-hoc propensity-weighted analysis	HIST vs LIST or no statin group
	IVUS assessment of coronary calcification and percent atheroma volume (PAV)	• HIST (N = 1545): High intensity statin therapy ATORVA 80 mg/d, ROSUVA 40 mg/d	↓ PAV
		• LIST (N = 1726): Low intensity statin therapy ATORVA $<$ 40 mg/d, ROSUVA $<$ 20 mg/d, SIMVA $<$ 40 mg/d, PRAVA $<$ 80 mg/d, LOVA $<$ 20 mg/d, FLUVA $<$ 40 mg/d	↑ coronary calcification
		• No-statin therapy (N = 224)
Dykun I et al. (2016) [125]	3483 participants;	• Observational study	↑ CAC
	EBT: CAC progression	• 230 pts on statins at baseline	↓ coronary events
		• FU median duration: 5 y
Coronary calcification
Raggi P et al. (2005) [116]	475 hyperlipidemic, postmenopausal women;	• RCT: Group A (N = 218): intensive statin ATORVA 80 mg; Group B (N = 257): moderate statin therapy, PRAVA 40 mg	Group A vs group B:
	EBT: CAC	• Duration: 12 mo	↔ CAC
			↓ LDL
Houslay ES et al. (2006) [117]	102 pts w/ calcific AS; Helical CT: CAC	• RCT: Group A (N = 48): ATORVA 80 mg; Group B (N = 54): matched placebo	Group A vs group B:
		• Duration: median FU 24 mo	↔ CAC
Terry JG et al. (2007) [114]	80 pts w/ asymptomatic vascular disease, HDL $<$ 50 mg/dL, 100 $<$ LDL $<$ 160 mg/dL, $>$ 2 other CV risk factors, CAC score $>$ 50;	• RCT: Group A (N = 40): SIMVA 80 mg; Group B (N = 40): placebo	Group A vs group B:
	MDCT: CAC	• Duration: 12 mo	↑ CAC, AAC
			↓ TC, TG, LDL
Andelius L et al. (2018) [131]	12 studies, 692 participants;	• Systematic review & meta-analysis	Intensive vs moderate statin therapy:
	CCTA: plaque volume, plaque calcification, calcium intensity signal	• Intensive statin therapy (N = 99)	↓ non-calcified plaque volume,
		• Moderate statin therapy (N = 404)	↑ calcified plaque volume ↑calcium signal intensity
		• Controls (N = 189)
		• FU: 14.5 $\pm$ 9.5 months
Lee SE et al. (2018)	1255 pts;	• Prospective multinational registry: Group A (N = 781): statin receivers; Group B (N = 474): statin naïve	Group A vs group B:
PARADIGM study [135]	CCTA: CAC progression	• Duration: $\geq$ 2-year interval	↓ atheroma volume
			↓ non-calcified and ↓ high risk plaques
			↑ plaque calcification
Lee SE et al. (2019)	654 pts;	• Prospective multinational registry: Group A (N = 408): statin receivers; Group B (N = 246): non-statin	Group A vs group B:
PARADIGM study [134]	CCTA: CAC progression	• Duration: $\geq$ 2-year interval	↑ calcified plaque volume
			↓ non-calcified plaque volume progression
Scott et al. (2022)	142 participants;	• Prospective, cohort study, sub-analysis of RIGHT study: Group A (N = 66): high hs-CRP; Group B (N = 76): low hs-CRP	Group A vs B:
RIGHT study [109]	CCTA: coronary calcification	• Duration: 2 years	↑ DCB
			↔ NCB
Carotid artery disease
Kadoglou NPE et al. (2008) [151]	97 pts w/ carotid stenosis $>$ 40%, w/o indication of revascularization	• Prospective study	ATORVA:
	52 age-& sex-matched controls;	• ATORVA (10 mg–80 mg) target LDL-C $<$ 100 mg/dL	↑ GSM score
	GSM score	• Controls at baseline	↓ OPG, OPN
	OPG, OPN	• Duration: 6 mo
Kadoglou NPE et al. (2010) (JVS) [73]	140 pts w/ moderate carotid stenosis w/o indication of revascularization;	• RCT: Group A (N = 70): Low-dose ATORVA (10 mg–20 mg) target LDL-C $<$ 100 mg/dL; Group B (N = 70): High-dose ATORVA (80 mg) target LDL-C $<$ 70 mg/dL	High-dose vs Low-dose ATORVA:
	GSM score	• Duration: 12 mo	↑ GSM score
	OPG, OPN		↓ OPG, OPN
Kadoglou NPE et al. (2010) (EJVS) [152]	113 pts w/ bilateral carotid atherosclerosis;	• Group A (N = 46): Ipsilateral carotid revascularization; Group B (N = 67): Bilateral low-grade stenosis	Group A vs group B:
	GSM score	• Both groups received ATORVA 10–80mg, LDL target $<$ 100 mg/dL	↑ GSM score contralateral
	OPG, OPN	• Duration: 6 mo	↓ OPG, OPN
Mujaj B et al. (2018). The Rotterdam study [121]	1740 pts, age $>$ 45 years old w/ carotid atherosclerosis; carotid MRI	• prospective population-based cohort study.	Higher dose and longer use of statins:
		• statin exposure: 30.2% of participants	↑ carotid plaque calcification
		• Median duration exposure: 48 mo

AAC, abdominal aortic calcium; AS, aortic stenosis; ATORVA, atorvastatin; CAC, coronary artery calcium; CCTA, coronary computed tomography angiography; CV, cardiovascular; CVD, cardiovascular disease; DCB, dense-calcified coronary burden; EBT, electron-beam tomography; EZET, ezetimibe; FLUVA, fluvastatin; FU, follow-up; GP, general practitioner; GSM, grey scale median; HDL, high-density lipoprotein; HIST, high intensity statin therapy; hs-CRP, high-sensitivity C-reactive protein; LIST, low intensity statin therapy; LDL, low density lipoprotein; LOVA, lovastatin; MDCT, multi-detector computed tomography; NCB, noncalcified coronary burden; pts, patients; PAV, percent atheroma volume; PITAVA, pitavastatin; PRAVA, pravastatin; RCT, randomized control trial; ROSUVA, rosuvastatin; SIMVA, simvastatin; TC, total cholesterol; TG, triglycerides; w/, with; w/o, without; VH-IVUS, virtual histology intravascular ultrasound; CT, computed tomography; OPN, osteopontin; OPG, osteoprotegerin.