Ezetimibe/statin combination therapy more effective in LDL-c lowering than statin uptitration

Changes in LDL-C levels and goal attainment associated with addition of ezetimibe to simvastatin, atorvastatin, or rosuvastatin compared with titrating statin monotherapy

Literature - Foody, Vasc Health Risk Manag. 2013 - Vasc Health Risk Manag. 2013;9:719-727

Foody JM, Toth PP, Tomassini JE, et al.
Vasc Health Risk Manag. 2013;9:719-727. Epub 2013 Nov 15


Although statin therapy is highly effective in lowering LDL-c levels and reducing cardiovascular (CV) risk [1-3],  for many patients with high risk of coronary heart disease (CHD) the obtained effect with statins is not sufficient. Clinical guidelines recommend more intensive LDL-c lowering therapy to achieve LDL-c targets, including uptitration of statins to maximally tolerated doses, and/or combination therapy [2,3].
For some patients, combination therapy may be the better option, since they may not tolerate higher statin doses. Addition of ezetimibe to statin therapy has been shown to improve lowering of LDL-c levels, as opposed to statin therapy alone, and is generally well tolerated in various patient populations [4].
This study evaluated the effect of adding ezetimibe to simvastatin, atorvastatin or rosuvastatin therapy on LDL-c changes and goal attainment, in comparison to titrating these statins in CHD/CHD-risk equivalent patients, by making use of data from a large US managed-care database. Baseline was defined as up to 6 months before the add-on or titration date (index date) and follow-up as up to 12 months after the index date.

Main results

  • Mean LDL-c levels at baseline were significantly higher in the add-on groups for each statin (2.9-3.1 mmol/L, [113-118 mg/dL]) as compared to the titrate groups (2.6-2.8 mg/dL [102-108 mg/dL]).
  • At follow-up, LDL-c reduction was highest in the add-on groups (2.1-2.2 mmol/L [80-85 mg/dL]) than in the titrator groups (2.3-2.5 mmol/L [87-95 mg/dL]). Both absolute and percent changes were significantly greater in the add-on groups.
  • At baseline, more people in the titrator groups had LDL-c levels below 1.8 and 2.6 mmol/L [70 and 100 mg/dL] than in the add-on groups for all statins.
  • At follow-up, goal attainment was significantly larger when ezetimibe was added on for each statin group, as compared with uptitration.
  • Multivariate models showed that the adjusted difference in percent change from baseline was larger after addition of ezetimibe than after statin uptitration, and the likelihood of achieving an LDL-c goal was 2.5-3.2 times higher for add-on therapy.

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This study shows that in a real-world setting, addition of ezetimibe to ongoing statin monotherapy can improve LDL-c lowering and goal attainment, as compared to uptitration of statin dose. Uptitration of statin dose also lowered LDL-c. High-risk CHD patients in need of more intensive LDL-c lowering therapy may benefit from thus benefit from more intensive statin therapy or combination therapy of ezetimibe in addition to statins. Whether ezetimibe/statin combination therapy comparably lowers CV risk like high-potency statins remains to be determined.

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1. Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753): 1670–1681.
2. Catapano AL, Reiner Z, De Backer G, et al. ESC/EAS Guidelines for the management of dyslipidaemias. The Task Force for the manage­ment of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis. 2011;217(1):3–46.
3. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. J Am Coll Cardiol. 2004;44(3):720–732.
4. Catapano AL, Toth PP, Tomassini JE, Tershakovec AM. The efficacy and safety of ezetimibe co-administered with statin therapy in various patient groups. Clin Lipidol. 2012;8(1):13–41.

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