Effect of Atorvastatin Therapy on Fibrous Cap Thickness in Coronary Atherosclerotic Plaque as Assessed by Optical Coherence Tomography: The EASY-FIT Study

Komukai K, Kubo T, Kitabata H et al.,
J Am Coll Cardiol. 2014 Dec 2;64(21):2207-17
 Progression of atherosclerosis has been shown to be attenuated by statin therapy [1-3]. More precisely, angioscopy studies demonstrated that statins decreased plaque yellow score, which may reflect the lipid content of coronary plaques [4]. The precise mechanism of how statins stabilise plaques is, however, unclear.
Plaques can be characterised with intravascular optical coherence tomography (ICT) with high resolution [5]. Fibrous cap thickness can be measured, postulated to be in important factor in plaque vulnerability.
The EASY-FIT (Effect of AtorvaStatin therapY on FIbrous cap Thickness in coronary atherosclerotic plaque as assessed by optical coherence tomography) study was a prospective, randomised OCT study in Japan, which evaluated the effect of atorvastatin 20 mg/day (the highest approved dose in Japan) vs. 5 mg/day (standard dose) on fibrous cap thickness in coronary atherosclerotic plaque. Successful OCT at baseline and follow-up was performed in 60 patients with successful percutaneous coronary intervention (PCI) for unstable angina pectoris and untreated dyslipidaemia. The target lesion for OCT was a non-culprit lesion in the PCI-treated artery. Median follow-up time was 12.0 months (IQR: 11.6-12.2 months) in those randomised to 20 mg/day and 11.9 months (IQR: 11.3-12.4) in those receiving 5 mg/day of atorvastatin. No cardiac death or myocardial infarction occurred.

Main results

• The percentage decrease in serum LDL-c was significantly greater in those receiving atorvastatin 20 mg/day than those on 5 mg/day (-46%, IQR: -56% to -39%, vs. -38%, IQR: -47% to -23%, P=0.009).
• Fibrous cap thickness increased significantly in both groups, but more so in the group randomised to 20 mg/day (69%, IQR: 25-104%) than those receiving 5 mg/day (17%, IQR: -1% vs. 34%, P<0.001).
• The lipid arc decreased significantly in both groups (20 mg/day: -27%, IQR: -37 to -20%, vs. 5 mg/day: -8%, IQR: -13 to -4%, P<0.001).
• The percentage of plaques with macrophage accumulation at baseline was similar in both groups, and no plaques were seen that newly acquired or were absolutely depleted of macrophages at follow-up. Macrophage grade did decrease significantly in both groups, but to a larger extent in the 20 mg/day group (-38%, IQR: -44 to -31% vs. -24%, IQR: -33% to 0%, P<0.001).
• The percentage change in fibrous cap thickness was significantly negatively correlated with %change in serum LDL-c, MDA-LDL, hs-CRP and MMP-9, but not with %change in total cholesterol, HDL-c, triglyceride, IL-6 and HbA1c.
• The %change in macrophage grade was negatively correlated with %change in serum HDL-c, and positively correlated with serum hs-CRP and MMP-9 levels, but not with the other biomarkers. %Change in macrophage grade also negatively correlated with the %change in fibrous cap thickness.

Conclusion

Therapy with atorvastatin 20 mg/day yielded in a larger increase in fibrous cap thickness and a decrease in lipid arc and macrophage grade than did 5 mg/day. The increased thickness of the fibrous cap was associated with a decrease of unfavourable biomarkers. This study suggests that treatment with atorvastatin 20 mg/day may stabilise coronary atherosclerotic plaques more so than 5 mg/day.

Find this article on Pubmed

References

1. Nissen SE, Tuzcu EM, Schoenhagen P, et al. Effect of intensive compared with moderate lipid lowering therapy on progression of coronary atherosclerosis. A randomized controlled trial.JAMA 2004;291:1071–80.
2. Okazaki S, Yokoyama T, Miyauchi K, et al. Early statin treatment in patients with acute coronarysyndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event: the ESTABLISH Study.Circulation 2004;110:1061–8.
3. Hiro T, Kimura T, Morimoto T, et al. Effect of intensive statin therapy on regression of coronaryatherosclerosis in patients with acute coronary syndrome. A multicenter randomized trial evaluated by volumetric intravascular ultrasound using pitavastatin versus atorvastatin (JAPAN-ACS [Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome] Study) Clinical Trials. J Am Coll Cardiol 2009;54:293–302.
4. Takano M, Mizuno K, Yokoyama S, et al. Changes in coronary plaque color and morphology by lipid-lowering therapy with atorvastatin: serial evaluation by coronary angioscopy. J Am Coll Cardiol 2003;42:680–6.
5. Tearney GJ, Regar E, Akasaka T, et al. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the international working group for intravascular optical coherence tomography standardization and validation. J Am Coll Cardiol 2012;59:1058–72.