This slide is taken from the NICE technology Appraisal for Ezetrol, they stated hat there is no point in doubling or switching statins as you only get a 6% or 8% further reduction, just adding in Ezetrol gives you a further 23% reduction.
NICE do not at any point recommend Atorvastatin or Rosuvastatin, as per the green box whenever they say HIGHER INTENSITY STATIN this just means Simvastatin 80mg
This is the local guidance for every GP in Derbyshire which says Ezetimibe should be used as per NICE guidance so all of primary care and secondary care are free to use Ezetrol.
As we have seen, dietary cholesterol accounts for a relatively small proportion of circulating cholesterol21. From a typical dietary intake of 300-700 mg/day21 about half is absorbed in the small bowel and transported to the liver. In the liver it joins the pool of cholesterol which has been synthesised de novo within the liver. Approximately one-third of this is released into the circulation as part of a lipoprotein molecule, while the remainder, approximately 1,000 mg/day is excreted back into the bowel via the bile21. Overall, 50% of cholesterol in the intestine is absorbed and metabolised, and 50% is excreted in the faeces21.
Ezetimibe: metabolism—low systemic exposure to ezetimibe Three hours after intravenous administration to rats, the majority of radioactively labeled ezetimibe localized to the intestinal lumen and some of it was associated with the intestinal wall. In contrast, minute ezetimibe-derived radioactivity was found in plasma, liver, or bile. Therefore, although ezetimibe is technically a &quot;systemic&quot; drug because of its enterohepatic circulation and recirculation, the low systemic exposure of ezetimibe may help reduce its potential for systemic adverse effects and for drug interactions. Reference: van Heek M, Farley C, Compton DS, et al. Comparison of the activity and disposition of the novel cholesterol absorption inhibitor, SCH58235, and its glucuronide, SCH60663. Br J Pharmacol 2000;129:1748-1754.
This is a paper where they compared Statins to Non Statins in an 82000 patient Meta-Analysis to se if it mattered how LDL was reduced, they found that it didn’t matter how LDL was reduced the reduction in LDL correlated with the reduction in events. The POSCH trial was a study where they used surgery to block the absorption of Cholesterol and this was just as effective as Statins in terms of outcomes.
Simva 40mg and Ezetimibe 10mg is more powerful than Atorva 80mg in reducing LDL, no need to titrate and switch to Atorva but more sense to add in Ezetrol.
Adding in Ezetimibe gives you a 9% increase in HDL, if you swiched a ptient over to Atirva 80 then their HDL would be reduced as this onlky gives an increase of 1.4%.
57% of patients reached an LDL of 1.8mmol on Eze and Simva 40 compared to 36% on Atorva 80mg.
Looking specifically at simvastatin27, ezetimibe resulted in significant mean LDL-C decreases of 44-57% depending on the dose of simvastatin. This slide shows the effect of simvastatin ± ezetimibe 10 mg o.d. on LDL-C across the full statin dose regimen. Significant decreases in LDL-C are seen with ezetimibe plus any dose of simvastatin, however this slide demonstrates clearly that ezetimibe 10 mg o.d. plus simvastatin 10 o.d. provides comparable efficacy to simvastatin 80 mg o.d. – both reducing LDL-C by 44% over the 12 weeks of the trial27.
Looking specifically at atorvastatin, ezetimibe resulted in significant mean LDL-C decreases of 50-60% depending on the dose of atorvastatin28. This slide shows the effect of atorvastatin ± ezetimibe 10 mg o.d. on LDL-C across the full statin dose regimen. Significant decreases in LDL-C are seen with ezetimibe plus any dose of atorvastatin, however this slide demonstrates clearly that ezetimibe 10 mg o.d. plus atorvastatin 10 mg o.d. provides comparable efficacy to atorvastatin 80 mg o.d. – both reducing LDL-C by around 50% over the 12 weeks of the trial28.
Ezetimibe And Lipids - Dr Vivek Baliga Reviews
Lipid Management and
Dr Vivek Baliga
Baliga Diagnostics Pvt Ltd
• Lipid-lowering therapy in patients with
hypercholesterolemia has a proven
survival benefit for both primary prevention
(ie, in patients without clinical evidence of
coronary disease) and secondary
prevention (ie, in patients with established
coronary disease), even when serum
cholesterol concentrations are "normal"
Methods of action
• Regression of atherosclerosis
• Plaque stabilization
• Reduced inflammation
– Reduction in CRP
– Reduction in Serum Amyloid A
• Decreased thrombogenicity
• Reversal of endothelial dysfunction
• Reduction in ventricular arrhythmias
Drug class Serum LDL Serum HDL Serum TG
↓ 20 to 60
↑ 5 to 10
↓10 to 33
Ezetimibe ↓ 17 percent No change No change
↓ 15 to 30
0 to slight
Nicotinic acid ↓ 10 to 25
↑ 15 to 35
↓ 25 to 30
• Cholesterol absorption inhibitors
• Impair dietary and biliary cholesterol
absorption at the brush border of the
intestine without affecting the absorption
of triglycerides or fat soluble vitamins
• Mechanism of action may involve
Niemann-Pick C1 like 1 (NPC1L1) protein
or an associated protein involved in
• Elevated levels of LDL-C are highly correlated with the risk of CVD
• Reducing LDL-C is associated with a reduced risk of CV events in
people with, or at high risk of, CVD
• Doubling the dose of statin reduces baseline LDL-C by ~6%
• Switching to an alternative statin reduces baseline LDL-C by ~8%
• Greater reductions of LDL-C, up to 23.2% post-statin baseline are
seen when ezetimibe added to statin therapy
• Ezetimibe co-administered with a statin was found to have a similar
adverse event profile compared with statin therapy alone
1. National Institute for Health and Clinical Excellence. Ezetimibe for the treatment of primary (heterozygous-familial and non-familial)
hypercholesterolaemia. Technology Appraisal Guidance 132. November 2007.