Dear Editor
We read with interest the retrospective study of Kern et al.Citation1, which included >2 million patients with newly diagnosed dyslipidemia at risk for coronary heart disease (CHD). Only 15% of this population received statinsCitation1. Drugs other than statins (ezetimibe, fibrates, niacin, bile acid sequestrants and omega-3 fatty acids) were used in <1% of patientsCitation1.
The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) showed that adding ezetimibe to simvastatin significantly reduced cardiovascular events (cardiovascular death, myocardial infarction, rehospitalization for unstable angina, coronary revascularization or stroke) when compared with simvastatin monotherapy in 18,144 patients with acute coronary syndromes (34.7 vs 32.7%, p = 0.016)Citation2. This finding is supported by genetic evidence showing that subjects with mutations that disrupt the enteral cholesterol transporter (NPC1L1) function (the target for ezetimibe action) have lower plasma low density lipoprotein cholesterol (LDL-C) levels and a reduced risk of CHDCitation3.
Ezetimibe may also exert anti-inflammatory, anti-atherogenic and antioxidant actionsCitation4. However, the relevance of these actions remains to be established. Meta-analyses showed that adding ezetimibe decreases LDL-C levels more than statin monotherapy (by ≈24%)Citation5. Also, adding ezetimibe was more effective at lowering LDL-C levels than doubling the dose of statinsCitation6. Other meta-analyses have confirmed this increased lowering of LDL-CCitation7.
Barkas et al.Citation8 reported that adding ezetimibe to statins led to higher rates of LDL-C target achievement according to the American College of Cardiology/American Heart AssociationCitation9 or European Society of Cardiology/European Atherosclerosis SocietyCitation10 guidelinesCitation8.
Smoking status and family history of CHD were not available in the Kern et al.Citation1 study, as acknowledged by the authors. This means that some of the study population would probably be included in higher risk groups.
Transparency
Declaration of funding
This letter was not funded.
Declaration of financial/other relationships
This letter was written independently. The authors did not receive financial or professional help with the preparation of the manuscript. D.P.M. has disclosed that he has given talks, attended conferences and participated in studies sponsored by Merck, Sharp & Dohme and Genzyme. A.P.A. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article. A.P.A. is supported by a grant from the Hellenic Atherosclerosis Society.
References
- Kern DM, Balu S, Tunceli O, et al. Statin treatment patterns and clinical profile of patients with risk factors for coronary heart disease defined by National Cholesterol Education Program Adult Treatment Panel III. Curr Med Res Opin 2014;30:2443-51
- Kohno T. Report of the American Heart Association (AHA) Scientific Sessions 2014, Chicago. Circ J 2014; in press
- Stitziel NO, Won HH, Morrison AC, et al. Inactivating mutations in NPC1L1 and protection from coronary heart disease. N Engl J Med 2014;371:2072-82
- Katsiki N, Theocharidou E, Karagiannis A, et al. Ezetimibe therapy for dyslipidemia: an update. Curr Pharm Des 2013;19:3107-14
- Mikhailidis DP, Sibbring GC, Ballantyne CM, et al. Meta-analysis of the cholesterol-lowering effect of ezetimibe added to ongoing statin therapy. Curr Med Res Opin 2007;23:2009-26
- Mikhailidis DP, Lawson RW, McCormick AL, et al. Comparative efficacy of the addition of ezetimibe to statin vs statin titration in patients with hypercholesterolaemia: systematic review and meta-analysis. Curr Med Res Opin 2011;27:1191-210
- Gudzune KA, Monroe AK, Sharma R, et al. Effectiveness of combination therapy with statin and another lipid-modifying agent compared with intensified statin monotherapy: a systematic review. Ann Intern Med 2014;160:468-76
- Barkas F, Milionis H, Kostapanos MS, et al. How effective are the ESC/EAS and 2013 ACC/AHA guidelines in treating dyslipidemia? Lessons from a lipid clinic. Curr Med Res Opin 2014;1-8 . [Epub ahead of print]
- Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2889-934
- Reiner Z, Catapano AL, 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). Eur Heart J 2011;32:1769-818