Newly Initiated Statin Therapy After ACS Reduces Plaque Burden Within Six Weeks

September 15, 2009

September 15, 2009 (Quebec, Quebec City) — Initiating statin therapy following an acute coronary syndrome (ACS) results in a rapid and significant reduction in coronary atherosclerotic plaque burden as assessed by intravascular ultrasound (IVUS), a new study has shown [1]. Investigators report that this antiatherosclerotic effect was observed after six weeks and was partly associated with decreases in total- and LDL-cholesterol levels, as well as reductions in C-reactive protein (CRP).

"We are talking about plaque burden, the volume of atherosclerosis," lead investigator Dr Josep Rodés-Cabau (Quebec Heart and Lung Institute, QC) told heartwire . "We are not talking about characteristics of the plaque or about vulnerable plaque, but what the study shows is that initiating statin therapy immediately following an ACS is doing something very quickly. This is the first study to show that within a very short period of time, you can have significant effects on the atherosclerotic plaques."

The results of the study, a post hoc analysis of the Effects of Reconstituted High-Density Lipoprotein on Atherosclerosis-Safety and Efficacy (ERASE) trial, are published in the September 15, 2009 issue of the American Journal of Cardiology.

No Studies Explaining Early Benefit of Statins

In an interview with heartwire , Rodés-Cabau said that several IVUS studies have shown that intensive lipid-lowering therapy is associated with a reduction of atherosclerotic disease progression and even a possible regression of plaque burden at one to two years. There are data showing that the early initiation of lipid-lowering therapy in the ACS setting is associated with clinical benefit, although the mechanism explaining this early benefit is unknown, he added. No studies, however, have examined the acute effects of statin therapy on atherosclerotic plaque, partly because patients would have to undergo a second IVUS shortly after the baseline scan.

In this study, which included 74 patients who were included in the ERASE trial, a study investigating the effects of four weekly reconstituted HDL-cholesterol infusions on coronary atherosclerosis, investigators studied the effects of statin therapy initiated after ACS in 36 statin-naive patients. Patients treated with statins prior to the ACS served as the control group. All patients underwent an IVUS examination at baseline and then again approximately six weeks later to assess the short-term effects of newly initiated statin therapy on plaque volume.

Statins were prescribed at the discretion of the physician, with atorvastatin 40 mg the most common regimen in both treatment groups. Compared with patients treated with long-term statin therapy prior to the ACS, those newly prescribed the lipid-lowering drugs had significant reductions in plaque burden from baseline as assessed by the percentage and nominal changes in atheroma volume. The results were adjusted for baseline characteristics as well as for recombinant HDL therapy in the ERASE trial.

ERASE: IVUS Results in the Statin-Therapy Arms

IVUS measure Long-term statin therapy before ACS (n=38) Newly initiated statin therapy after ACS (n=36) p (between groups)
Atheroma volume percentage change -0.54 -4.71 0.002
p, follow-up vs baseline 0.546 <0.0001 --
Nominal change in atheroma volume (mm3) 1.21 -9.10 0.003
p, follow-up vs baseline 0.429 <0.0001 --

Rodés-Cabau said two studies, PROVE-IT and MIRACL, have shown that starting these lipid-lowering drugs immediately after an ACS was associated with significant reduction in cardiovascular events. As reported previously by heartwire , the benefits in both trials occurred early, 30 days in PROVE-IT and after 16 weeks in MIRACL.

The group also showed that there was a relationship between changes in total cholesterol, LDL cholesterol, and the ratio of total- to HDL-cholesterol levels such that larger reductions in the lipid measures were associated with larger percentage changes in atheroma volume after six weeks. Similarly, there was a relationship with CRP levels, although this association was not as strong, partly because CRP was measured up to 14 days after the IVUS examination.

Commenting on the lack of regression with long-term statin therapy, Rodés-Cabau pointed out that there was no progression of plaque burden for these patients. The findings, however, point to the distinct differences between patients already on statins and those newly prescribed the drugs, which could make a difference in interpreting the results of future clinical trials, typically two years for most IVUS studies.

The ERASE trial was funded by CSL (Victoria, Australia), but no conflicts of interest were reported for this analysis.

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