A study that appeared in the Nov. 5, 2003 edition of the Journal of the American Medical Association* provided strong evidence that five weekly infusions of a synthetic form of "good cholesterol," or HDL, can possibly remove significant amounts of plaque from coronary arteries.
Study details
The ApoA-I Milano trial involved 57 acute coronary syndrome patients in a randomized, prospective, double-blind, multicenter clinical trial conducted from November 2001 to March 2003. All patients had experienced an acute coronary syndrome, either unstable angina (severe chest pain) or heart attack. Each patient had a single coronary artery examined using IVUS (intravascular ultrasound) within two weeks following the cardiac event. Patients were randomized to three treatment groups — placebo, low dose or high dose of intravenous recombinant ApoA-I Milano/phospholipid complex. The study drug was administered as a weekly intravenous infusion for a total of five weeks. Patients underwent IVUS of the originally imaged coronary artery for a second time within two weeks following the final infusion. The second images then were compared with baseline images to compare plaque levels. Researchers found a statistically significant change in volume of the thickened, fatty lining inside the arteries of patients who had received either the high or the low dose of intravenous recombinant ApoA-I Milano/phospholipid complex.
Where are we now?
Heart and Vascular Institute cardiologist Steven E. Nissen, MD, who directed the 10-center nationwide study, cautions that, "Much more testing needs to be performed to determine whether this unique form of HDL can be used routinely to treat patients with atherosclerosis." He emphasized that the 2003 clinical trial was a small "proof of concept" study, designed only to demonstrate the potential of this new therapy. "People should not view new therapies as a 'magic-bullet' cure. For most of us, medicines will never replace the need to make healthy lifestyle choices," Nissen said.
At this time, physicians and researchers are planning for future studies of Apo A1-Milano. The process to produce this drug and design a study of this type can take several years. There is no currently active protocol or a waiting list for enrollment for Apo A-1 Milano trials.
Lipid lowering very important
On the other hand, other studies that have come about since the Apo A-1 Milano trial have provided promising results for statins, halting progression and even promoting regression of plaque.
- A REVERSAL trial showed that high doses of lipitor can halt progression of coronary artery disease. This study compared two cholesterol lowering drugs (pravastatin and atorvastatin) and found that lower levels of LDL-C, as low as 60 mg/dl (much lower than the previous National Cholesterol Education Program * (NCE) guidelines) had better outcomes.
- PROVE-IT also found that aggressive lipid lowering does achieve a reduction in the incidence of unstable angina, death, heart attack and need for revascularization in patients post acute coronary syndrome, with an LDL-C goal of 60 - 70 mg/dl.
- PROVE-IT and REVERSAL caused the National Cholesterol Education Program* to re-look at current guidelines and adjust its LDL-C goals for very high risk individuals to less than 70 mg/dl.
- PROVE-IT and REVERSAL investigators next looked at c-reactive protein or CRP. They found that intensive lipid lowering also lowers risk of progression by decreasing levels of CRP, a measure of inflammation in the body, as well as lowering LDL-C levels. Dr. Nissen stated, "These findings strongly suggest that we should target statin therapy at reducing CRP, not just cholesterol."
- ASTEROID (A Study to Evaluate the Effect of Rosuvastatin On Intravascular Ultrasound-Derived Coronary Atheroma Burden), the latest study, found a reduction in the size of atherosclerotic plaque with use of a medication to raise HDL-C and significantly lower LDL-C. This study only looked at plaque size, not incidence of clinical events.
- While more research is needed to help stop or regress atherosclerosis or coronary artery disease, great strides are being made to achieve this goal.
- Patients should discuss lipid therapy with their physician. Each patient is treated individually based on their medical history and lab values.
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