EASE trial
New Orleans, LA - The results of a recent study designed to assess the effectiveness of ezetimibe (Zetia, Merck & Co/Schering-Plough) used concomitantly with statin therapy have shown the combination to be more effective in reducing LDL cholesterol than statin therapy alone.
The study, known as the Ezetimibe Add-on to Statin for Effectiveness (EASE) trial and presented during the late-breaking clinical trials session at the American College of Cardiology 2004 Scientific Sessions, showed that the coadministration of ezetimibe and statin therapy provided greater reductions in LDL cholesterol compared with statin therapy alone. More patients treated with the combination also achieved LDL cholesterol levels set out by the National Cholesterol Education Program (NCEP) ATP III guidelines than those treated with statin only.
"The evidence base for cholesterol lowering and getting LDL cholesterol to goal is increasing from this meeting, but perhaps the main limitation still remains getting cholesterol to target," Dr Thomas Pearson (University of Rochester, NY) told the media during a press conference after the late-breaking session. He explained that in statin-treated patients who failed to reach NCEP cholesterol targets, the coadministration of ezetimibe further reduced LDL cholesterol by 23% compared with those patients who remained on statin therapy alone.
Treating to target
The EASE trial was a large, community-based clinical study involving more than 3000 patients currently being treated with statin therapy but who exceeded LDL cholesterol levels established by NCEP guidelines.
Patients were randomized 2:1 to treatment with ezetimibe 10 mg or to placebo, with 2020 patients randomized to statin therapy plus ezetimibe and 1010 patients continuing with statin therapy alone. Within the trial, patients were treated with atorvastatin, simvastatin, pravastatin, fluvastatin, and lovastatin, with 62% on the starting dose of the drugs.
EASE: Percent change in LDL cholesterol
p<0.001 for all between-treatment groups
EASE: Percentage of patients achieving NCEP ATP III LDL cholesterol goals
p<0.001 for all between-treatment groups
"We conclude that ezetimibe 10 mg a day added to a stable dose of a statin significantly reduces LDL cholesterol from a statin baseline by an additional 23% compared with placebo," said Pearson. "It also significantly improved NCEP ATP III goal attainment."
In addition to LDL-cholesterol lowering, Pearson reported there were also significant improvements in other lipoprotein measurements, including triglycerides, HDL cholesterol, non-HDL cholesterol, and apolipoprotein B, with all favoring the ezetimibe and statin combination.
The combination was safe and well tolerated, with nonsignificant differences between the two study arms with regard to liver-enzyme elevations, added Pearson.
Diverse patient population
The study was conducted at 299 US sites and was representative of men and women, as well as African Americans, Hispanics, and individuals with diabetes and metabolic syndrome.
Pearson told the ACC audience that the benefit of ezetimibe and statin therapy compared with statin alone was consistent across the entire range of subgroups, reflecting a 25% further reduction in LDL-cholesterol lowering. Interestingly, the reduction was also consistent across the different statin brands and doses.
Simvastatin and ezetimibe superior to atorvastatin alone
With LDL cholesterol front and center at the ACC 2004 Scientific Sessions, the question of how low should it go also became one of how low can it go. A couple of Merck-sponsored studies looked at the combination of ezetimibe and simvastatin to identify the combination that could be safely used to reduce LDL cholesterol the most.
One study, led by Dr Christie Ballantyne (Baylor College of Medicine, Houston, TX), randomized patients to different treatment groups for four six-week periods, titrating the dose of the comparator atorvastatin from 10 mg to 80 mg and titrating the dose of simvastatin from 10 mg to 40 mg. Investigators compared ezetimibe 10 mg added to the various doses simvastatin with the various doses of atorvastatin. The primary end point of the study was percent change in LDL cholesterol from baseline.
In the first treatment period comparing low doses, Ballantyne and colleagues report that ezetimibe/simvastatin 10 mg and ezetimibe/simvastatin 20 mg provided greater reductions in LDL cholesterol compared with atorvastatin 10 mg alone. By the end of period four, when maximum doses were compared, ezetimibe/simvastatin 80 mg was superior to atorvastatin 80 mg in terms of LDL reduction (-59.4% vs -52.5%; p<0.01). Investigators also found that the combination of ezetimibe/simvastatin increased HDL cholesterol more than statin therapy alone.
A second Merck study showed that the coadministration of ezetimibe and simvastatin provided greater efficacy than doubling the dose of simvastatin in patients with type 2 diabetes. In these diabetic patients, who were also concomitantly being treated with thiazolidinediones, the investigators found the ezetimibe/simvastatin combinations were well tolerated and effective in reducing LDL cholesterol.
Pearson said the 23% reduction in LDL cholesterol seen in those patients receiving combination therapy has implications for clinical practice. This reduction, he said, compares favorably with the 6% to 8% reduction in LDL cholesterol usually obtained when a statin dose is doubled in patients not at goal.
"The addition of ezetimibe to statin therapy should be considered in patients who have not obtained the NCEP ATP III goals on statin therapy alone," concluded Pearson.
New Orleans, LA - The results of a recent study designed to assess the effectiveness of ezetimibe (Zetia, Merck & Co/Schering-Plough) used concomitantly with statin therapy have shown the combination to be more effective in reducing LDL cholesterol than statin therapy alone.
The study, known as the Ezetimibe Add-on to Statin for Effectiveness (EASE) trial and presented during the late-breaking clinical trials session at the American College of Cardiology 2004 Scientific Sessions, showed that the coadministration of ezetimibe and statin therapy provided greater reductions in LDL cholesterol compared with statin therapy alone. More patients treated with the combination also achieved LDL cholesterol levels set out by the National Cholesterol Education Program (NCEP) ATP III guidelines than those treated with statin only.
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Dr Thomas Pearson |
"The evidence base for cholesterol lowering and getting LDL cholesterol to goal is increasing from this meeting, but perhaps the main limitation still remains getting cholesterol to target," Dr Thomas Pearson (University of Rochester, NY) told the media during a press conference after the late-breaking session. He explained that in statin-treated patients who failed to reach NCEP cholesterol targets, the coadministration of ezetimibe further reduced LDL cholesterol by 23% compared with those patients who remained on statin therapy alone.
Treating to target
The EASE trial was a large, community-based clinical study involving more than 3000 patients currently being treated with statin therapy but who exceeded LDL cholesterol levels established by NCEP guidelines.
Patients were randomized 2:1 to treatment with ezetimibe 10 mg or to placebo, with 2020 patients randomized to statin therapy plus ezetimibe and 1010 patients continuing with statin therapy alone. Within the trial, patients were treated with atorvastatin, simvastatin, pravastatin, fluvastatin, and lovastatin, with 62% on the starting dose of the drugs.
EASE: Percent change in LDL cholesterol
| Change in LDL cholesterol | Statin therapy plus ezetimibe (%) (n=2020) | Statin therapy plus placebo (%) (n=1010) |
| Total | -25.8 | -2.7 |
| CHD/CHD risk equivalent | -25.1 | -1.1 |
| >2 risk factors | -23.8 | -4.1 |
| <2 risk factors | -25.7 | -5.8 |
p<0.001 for all between-treatment groups
EASE: Percentage of patients achieving NCEP ATP III LDL cholesterol goals
| NCEP ATP III cholesterol goals | Statin therapy plus ezetimibe (%) (n=2020) | Statin therapy plus placebo (%) (n=1010) |
| Total | 71.0 | 20.6 |
| CHD/CHD risk equivalent | 69.5 | 17.3 |
| >2 risk factors | 75.1 | 32.2 |
| <2 risk factors | 90.7 | 52.4 |
p<0.001 for all between-treatment groups
"We conclude that ezetimibe 10 mg a day added to a stable dose of a statin significantly reduces LDL cholesterol from a statin baseline by an additional 23% compared with placebo," said Pearson. "It also significantly improved NCEP ATP III goal attainment."
In addition to LDL-cholesterol lowering, Pearson reported there were also significant improvements in other lipoprotein measurements, including triglycerides, HDL cholesterol, non-HDL cholesterol, and apolipoprotein B, with all favoring the ezetimibe and statin combination.
The combination was safe and well tolerated, with nonsignificant differences between the two study arms with regard to liver-enzyme elevations, added Pearson.
Diverse patient population
The study was conducted at 299 US sites and was representative of men and women, as well as African Americans, Hispanics, and individuals with diabetes and metabolic syndrome.
Pearson told the ACC audience that the benefit of ezetimibe and statin therapy compared with statin alone was consistent across the entire range of subgroups, reflecting a 25% further reduction in LDL-cholesterol lowering. Interestingly, the reduction was also consistent across the different statin brands and doses.
Simvastatin and ezetimibe superior to atorvastatin alone
With LDL cholesterol front and center at the ACC 2004 Scientific Sessions, the question of how low should it go also became one of how low can it go. A couple of Merck-sponsored studies looked at the combination of ezetimibe and simvastatin to identify the combination that could be safely used to reduce LDL cholesterol the most.
One study, led by Dr Christie Ballantyne (Baylor College of Medicine, Houston, TX), randomized patients to different treatment groups for four six-week periods, titrating the dose of the comparator atorvastatin from 10 mg to 80 mg and titrating the dose of simvastatin from 10 mg to 40 mg. Investigators compared ezetimibe 10 mg added to the various doses simvastatin with the various doses of atorvastatin. The primary end point of the study was percent change in LDL cholesterol from baseline.
In the first treatment period comparing low doses, Ballantyne and colleagues report that ezetimibe/simvastatin 10 mg and ezetimibe/simvastatin 20 mg provided greater reductions in LDL cholesterol compared with atorvastatin 10 mg alone. By the end of period four, when maximum doses were compared, ezetimibe/simvastatin 80 mg was superior to atorvastatin 80 mg in terms of LDL reduction (-59.4% vs -52.5%; p<0.01). Investigators also found that the combination of ezetimibe/simvastatin increased HDL cholesterol more than statin therapy alone.
A second Merck study showed that the coadministration of ezetimibe and simvastatin provided greater efficacy than doubling the dose of simvastatin in patients with type 2 diabetes. In these diabetic patients, who were also concomitantly being treated with thiazolidinediones, the investigators found the ezetimibe/simvastatin combinations were well tolerated and effective in reducing LDL cholesterol.
Pearson said the 23% reduction in LDL cholesterol seen in those patients receiving combination therapy has implications for clinical practice. This reduction, he said, compares favorably with the 6% to 8% reduction in LDL cholesterol usually obtained when a statin dose is doubled in patients not at goal.
"The addition of ezetimibe to statin therapy should be considered in patients who have not obtained the NCEP ATP III goals on statin therapy alone," concluded Pearson.