Coronary interventions

Effect of rosuvastatin and eicosapentaenoic acid on neoatherosclerosis: the LINK-IT Trial

EuroIntervention 2019;15:e1099-e1106. DOI: 10.4244/EIJ-D-18-01073

Koji Kuroda
Koji Kuroda1, MD, PhD; Hiromasa Otake1, MD, PhD; Masakazu Shinohara2, MD, PhD; Masaru Kuroda1, MD, PhD; Shigeyasu Tsuda1, MD, PhD; Takayoshi Toba1, MD; Yuichiro Nagano1, MD; Ryuji Toh3, MD, PhD; Tatsuro Ishida1, MD, PhD; Toshiro Shinke1, MD, PhD; Ken-ichi Hirata1, MD, PhD
1. Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan; 2. Division of Epidemiology, Kobe University Graduate School of Medicine, Japan; 3. Division of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, Japan

Aims: We aimed to assess the effect of 10 mg/day of rosuvastatin plus eicosapentaenoic acid (EPA) versus 2.5 mg/day of rosuvastatin on the extent of neoatherosclerosis using optical coherence tomography (OCT).

Methods and results: We randomly assigned 50 patients with non-obstructive neoatherosclerotic plaques detected on OCT to receive either rosuvastatin 10 mg/day and EPA 1,800 mg/day (intensive therapy group) or rosuvastatin 2.5 mg (standard therapy group). Follow-up OCT was performed one year later to evaluate serial changes in neoatherosclerosis. The serum low-density lipoprotein cholesterol (LDL-C) level decreased significantly from baseline to 12-month follow-up in the intensive therapy group (89 mg/dL to 70 mg/dL; p<0.001), while no change occurred in the standard therapy group. Lipid index change and percent changes in macrophage grade were significantly lower in the intensive therapy group than in the standard therapy group (-53.6 vs 310.1, p=0.001; -37.0% vs 35.3%, p<0.001; respectively). Percent changes in lipid index and macrophage grade were positively correlated with the changes in serum LDL-C and C-reactive protein levels, and negatively correlated with the change in serum EPA/arachidonic acid and 18-hydroxyeicosapentaenoic acid (EPA bioactive metabolite) level.

Conclusions: Compared with rosuvastatin 2.5 mg/day, rosuvastatin 10 mg/day and EPA 1,800 mg/day significantly stabilised non-obstructive neoatherosclerotic plaques. Clinical Trial Registration: UMIN ID: UMIN000012576. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014711

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