Physicians' Academy for Cardiovascular Education

Larger increase in fibrous cap thickness in atherosclerotic plaque with higher dose statin

Komukai K et al., JACC 2014

 

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
 

Background

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.
 
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References

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