高用量のロスバスタチンとアトルバスタチンは動脈硬化を同程度に退縮（regress）させる（Abstract # 18600）

SATURN：高用量のスタチンはプラークを減らし冠動脈疾患の予測される進行を逆行させる
SATURN: High doses of statins reduce plaque and reverse expected progression of coronary artery disease
2種類のスタチン－ロスバスタチン（40mg）およびアトルバスタチン（80mg）－の高用量投与はアテローム容積を軽減することにより冠動脈疾患の進行を逆行させたとのlate-breaking researchの結果が2011年American Heart Association学会で発表され、New England Journal of Medicineに掲載された。215施設の患者1,385人を対象としたSATURN（Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin　血管内超音波検査による冠動脈アテロームの研究：ロスバスタチンとアトルバスタチンの効果比較）は、冠動脈内超音波を用いて冠動脈プラークを計測した最大規模のスタディである。過去のスタディでは、両薬剤ともLDLコレステロール低下には有効であったが、高用量のロスバスタチンがHDLコレステロールを7～15%上昇させたのに対し、アトルバスタチンのHDLに対する効果は少なかった。SATURNの24ヵ月間のプラークリグレッションの程度は両薬剤で同等であった（p=0.17；アテローム容積はアトロバスタチンにより0.99%減少しロスバスタチンにより1.22%減少した）。超音波の結果を他の方法で解析したところ、アテロームの総容積はアトルバスタチンにより4.4立方ミリメートル（p=0.01）、ロスバスタチンにより6.4立方ミリメートル（p<0.001）(群間比較でp=0.01）減少した。同様の患者に低用量の薬剤を投与した過去のスタディでは、心筋梗塞、脳卒中、または冠動脈形成術施行に至った患者が15～20%であったのに対し、SATURNではこれらのイベント発症率はその半分未満であった。
Full Text

High doses of two statins ― rosuvastatin (40 mg) and atorvastatin (80 mg) ― reversed the progression of coronary artery disease by reducing atheroma volume according to late-breaking research presented at the American Heart Association's Scientific Sessions 2011. The study was simultaneously published in the New England Journal of Medicine.

Involving 1,385 patients from 215 centers, SATURN (Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin) is the largest study using intracoronary ultrasound to measure changes in the amount of plaque in coronary arteries.

During 24 months, SATURN researchers compared the impact of two medications effective in lowering LDL cholesterol, but differing in their effect on HDL cholesterol.

In previous studies, high doses of rosuvastatin raised HDL cholesterol 7 percent to 15 percent while atorvastatin showed little effect on HDL cholesterol.

In the study's major finding the atheroma volume fell 0.99 percent with atorvastatin and 1.22 percent with rosuvastatin, a difference that was not statistically significant.

"Regression of plaque has been the holy grail of heart disease treatment, and in this trial more than two-thirds of the patients had regression," said Stephen J. Nicholls, M.D., Ph.D., lead researcher and cardiovascular director of the Cleveland Clinic Coordinating Center for Clinical Research in Ohio. "It's a very positive outcome for patients and shows the benefits of high doses of statins."

Among the study's other findings:

  • In another method of analyzing the ultrasound results (total atheroma volume), atorvastatin reduced plaque 4.4 cubic mm and rosuvastatin 6.4 cubic mm.
  • Atorvastatin reduced total plaque in 64.7 percent of patients and rosuvastatin in 71.3 percent of patients.
  • Average bad LDL cholesterol levels were 70 mg/dl in patients on atorvastatin and 62.6 mg/dl in patients on rosuvastatin;
  • Average good HDL cholesterol levels were 48.6 mg/dl with atorvastatin and 50.4 mg/dl with rosuvastatin.

"The differences between the two drugs were modest and the difference in HDL levels was less than we were anticipating based on previous studies," Nicholls said.

Study participants had undergone coronary angiography, usually because of chest pain and an abnormal stress test.
In previous studies on similar patients taking lower doses of medication, over two years, 15 percent to 20 percent experienced a myocardial infarction or stroke or underwent an angioplasty procedure to open a clogged artery. In SATURN, these events occurred at less than half that rate.

"Doctors have been reluctant to use high doses of statins, but in this study the drugs were safe, well tolerated and had a profound impact on lipid levels, the amount of plaque in vessel walls and the number of cardiovascular events," Nicholls said.

Co-authors are Christie M. Ballantyne, M.D.; Philip J. Barter, M.B.B.S., Ph.D.; M. John Chapman, Ph.D.; Raimund M. Erbel, M.D., Ph.D.; Peter Libby, M.D.; Joel S. Raichlen, M.D.; Kiyoko Uno, M.D.; Marilyn Borgman, R.N., B.S.N.; Kathy Wolski, M.P.H.; and Steven E. Nissen, M.D.

AstraZeneca funded the study.