Intensive lipid lowering therapy with titrated rosuvastatin yields greater atherosclerotic aortic plaque regression: Serial magnetic resonance imaging observations from RAPID study

Atherosclerosis. 2014 Jan;232(1):31-9. doi: 10.1016/j.atherosclerosis.2013.10.007. Epub 2013 Oct 30.

Abstract

Objective: Although previous randomized clinical trials established a basis for lipid guidelines worldwide, they employed fixed doses of statins throughout trials (fire-and-forget approach). In the real clinical setting, however, statin doses are titrated to achieve target low-density lipoprotein cholesterol (LDL-C) levels (treat-to-target approach). The major objective was to investigate whether intensive lipid-lowering therapy using the treat-to-target approach yielded greater regression of aortic plaques.

Methods: We therefore performed a prospective, randomized trial comparing the effects of standard (achieve LDL-C levels recommended by the Japanese guidelines) and intensive (achieve 30% lower LDL-C levels than standard) rosuvastatin therapy for 1 year in 60 hypercholesterolemic patients with a primary endpoint of aortic atherosclerotic plaques evaluated by non-invasive magnetic resonance imaging (MRI).

Results: Average doses were 2.9 ± 3.1 and 6.5 ± 5.1 mg/day for standard (n = 29) and intensive therapy group (n = 31), respectively. Although both therapies significantly reduced LDL-C and high-sensitivity C-reactive protein (hsCRP) levels, LDL-C reduction was significantly greater in the intensive group (-46 vs. -34%). MRI study showed that thoracic aortic plaques were significantly regressed in both groups, with greater regression of thoracic plaque in the intensive group (-9.1 vs. -3.2%, p = 0.01). Multivariate analyses revealed that thoracic plaque regression was significantly correlated with hsCRP reduction, but not with changes in serum lipids, endothelial function, or doses of rosuvastatin.

Conclusion: Intensive statin therapy with titration targeting lower LDL-C levels resulted in greater thoracic aortic plaque regression compared to standard therapy, which was correlated with hsCRP reduction, suggesting that intensive statin therapy could provide better clinical outcomes.

Keywords: Aortic plaques; Intensive therapy; MRI; Titration of rosuvastatin; hsCRP.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anthropometry
  • Aorta / pathology
  • Atherosclerosis
  • C-Reactive Protein / metabolism*
  • Cholesterol, LDL / blood*
  • Endothelium, Vascular / metabolism
  • Female
  • Fluorobenzenes / therapeutic use*
  • Guidelines as Topic
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Lipids / blood
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic / drug therapy*
  • Plaque, Atherosclerotic / pathology*
  • Prospective Studies
  • Pyrimidines / therapeutic use*
  • Rosuvastatin Calcium
  • Sulfonamides / therapeutic use*
  • Treatment Outcome

Substances

  • Cholesterol, LDL
  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Pyrimidines
  • Sulfonamides
  • Rosuvastatin Calcium
  • C-Reactive Protein