BARCELONA — Adding 10 mg/day of ezetimibe to maximum-dose rosuvastatin in a high-risk population enabled 94% of patients to achieve an LDL level below 100 mg/dL and 80% to get below 70 mg/dL, Dr. Christie M. Ballantyne reported at the joint meeting of the European Society of Cardiology and the World Heart Federation.
The combination also tripled the success rate in achieving both an LDL-cholesterol level below 70 mg/dL and a high-sensitivity C-reactive protein level (CRP) under 2.0 mg/L, compared with the results with 40 mg/day of rosuvastatin alone, added Dr. Ballantyne, professor of medicine at Baylor College of Medicine, Houston.
The National Cholesterol Education Program recommends the 70-mg/dL LDL target as an optional, more aggressive goal in very-high-risk patients. Getting the CRP below 2.0 mg/L is not recommended in any major guidelines; however, a secondary analysis of the PROVE-IT trial concluded that rates of recurrent MI or cardiovascular death were lower in patients who achieved their LDL target plus a CRP below 2.0 mg/dL than in those who met their LDL goal but had an elevated CRP, he explained.
Dr. Ballantyne reported on 469 high-risk patients in the United States, German-speaking Europe, and South Africa who participated in the Examination of Potential Lipid-Lowering Effects of Rosuvastatin in Combination With Ezetimibe Versus Rosuvastatin Alone (EXPLORER) trial. Subjects were randomized to 6 weeks of open-label daily rosuvastatin (Crestor) at 40 mg or to ezetimibe (Zetia) 10 mg plus rosuvastatin 40 mg. The mean baseline LDL cholesterol was 190 mg/dL, and more than one-third of EXPLORER participants had diabetes, a coronary heart disease (CHD) equivalent.
Patients who received combination therapy showed greater improvement than those with rosuvastatin alone in levels of LDL, CRP, and triglycerides, as well as the ratio of LDL to HDL cholesterol. (See table below.)
This was a high-risk population similar to patients enrolled in the Scandinavian Simvastatin Survival Study (4S) back in the 1990s, Dr. Ballantyne noted in an interview.
“The 4S study was … a landmark trial. They were able to reduce LDLs of 190 mg/dL by 35%, and it reduced events by 35% with a 42% decrease in CHD mortality. So to me it's amazing that here we are 12 years later and we're doing a study where we took LDLs of 190 and reduced them by 70%, down to a mean of 57 mg/dL, and with an LDL-to-HDL ratio of just about 1,” the physician said.
Both treatments were well tolerated. The price paid in terms of side effects for combination therapy's greater efficacy was limited to an increased incidence of abnormal liver function tests, rising from 0.4% with rosuvastatin alone to 2.5%. The laboratory abnormalities were readily reversed upon discontinuation of the ezetimibe.
“This has been a very useful combination in my practice,” Dr. Ballantyne continued. “I end up getting referred a lot of very tough patients who have high LDLs. … Now I'm seeing that even with my heterozygous familial hypercholesterolemia patients, I can add cholestyramine or niacin to this regimen and do a pretty good job—not everybody gets to target, but it's pretty impressive how many do compared to what we're used to.”
A large-scale, long-term randomized trial of the rosuvastatin/ezetimibe combination with clinical end points is not in the cards, since the drugs are marketed by different companies, he said. However, such a study is already underway comparing ezetimibe plus simvastatin with simvastatin alone. Both are made by AstraZeneca, which sponsored the EXPLORER trial.
Dr. Ballantyne has received research support and consulting fees from AstraZeneca and from Merck Schering Plough, which markets ezetimibe.
ELSEVIER GLOBAL MEDICAL NEWS
ELSEVIER GLOBAL MEDICAL NEWS