Hypercholesterolemia: Difference between revisions

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;Combination treatment
;Combination treatment
It is not clear that combination therapy is better than high dose [[hydroxymethylglutaryl-coenzyme A reductase inhibitor]]s.<ref name="pmid19884623">{{cite journal| author=Sharma M, Ansari MT, Abou-Setta AM, Soares-Weiser K, Ooi TC, Sears M et al.| title=Systematic review: comparative effectiveness and harms of combination therapy and monotherapy for dyslipidemia. | journal=Ann Intern Med | year= 2009 | volume= 151 | issue= 9 | pages= 622-30 | pmid=19884623
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19884623 | doi=10.1059/0003-4819-151-9-200911030-00144 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>
If treatment with a [[hydroxymethylglutaryl-coenzyme A reductase inhibitor]] does not achieve a desirable cholesterol, other drugs that have been studied include [[eicosapentaenoic acid]] which is a metabolite of [[fish oil]].<ref name="pmid17398308">{{cite journal |author=Yokoyama M, Origasa H, Matsuzaki M, ''et al'' |title=Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis |journal=Lancet |volume=369 |issue=9567 |pages=1090–8 |year=2007 |month=March |pmid=17398308 |doi=10.1016/S0140-6736(07)60527-3 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(07)60527-3 |issn=}}</ref> [[Ezetimibe]], a cholesterol-absorption inhibitor, was not clearly beneficial in a study of [[diabetes mellitus type 2]]<ref name="pmid18398080">{{cite journal |author=Howard BV, Roman MJ, Devereux RB, ''et al'' |title=Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes: the SANDS randomized trial |journal=JAMA |volume=299 |issue=14 |pages=1678–89 |year=2008 |month=April |pmid=18398080 |doi=10.1001/jama.299.14.1678 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=18398080 |issn=}}</ref> and a study of mixed [[primary prevention]] and [[secondary prevention]]<ref name="pmid18376000">{{cite journal |author=Kastelein JJ, Akdim F, Stroes ES, ''et al'' |title=Simvastatin with or without ezetimibe in familial hypercholesterolemia |journal=N. Engl. J. Med. |volume=358 |issue=14 |pages=1431–43 |year=2008 |month=April |pmid=18376000 |doi=10.1056/NEJMoa0800742 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=18376000&promo=ONFLNS19 |issn=}}</ref>. [[Niacin]] has been studied with improvements in the LDL and HDL<ref name="pmid17239888">{{cite journal |author=McKenney JM, Jones PH, Bays HE, ''et al'' |title=Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study) |journal=Atherosclerosis |volume=192 |issue=2 |pages=432–7 |year=2007 |month=June |pmid=17239888 |doi=10.1016/j.atherosclerosis.2006.11.037 |url=http://linkinghub.elsevier.com/retrieve/pii/S0021-9150(06)00733-7 |issn=}}</ref> with uncertain effects on [[carotid intima-media thickness]] <ref name="pmid15537681">{{cite journal |author=Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, Grace KA |title=Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins |journal=Circulation |volume=110 |issue=23 |pages=3512–7 |year=2004 |month=December |pmid=15537681 |doi=10.1161/01.CIR.0000148955.19792.8D |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=15537681 |issn=}}</ref>.
If treatment with a [[hydroxymethylglutaryl-coenzyme A reductase inhibitor]] does not achieve a desirable cholesterol, other drugs that have been studied include [[eicosapentaenoic acid]] which is a metabolite of [[fish oil]].<ref name="pmid17398308">{{cite journal |author=Yokoyama M, Origasa H, Matsuzaki M, ''et al'' |title=Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis |journal=Lancet |volume=369 |issue=9567 |pages=1090–8 |year=2007 |month=March |pmid=17398308 |doi=10.1016/S0140-6736(07)60527-3 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(07)60527-3 |issn=}}</ref> [[Ezetimibe]], a cholesterol-absorption inhibitor, was not clearly beneficial in a study of [[diabetes mellitus type 2]]<ref name="pmid18398080">{{cite journal |author=Howard BV, Roman MJ, Devereux RB, ''et al'' |title=Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes: the SANDS randomized trial |journal=JAMA |volume=299 |issue=14 |pages=1678–89 |year=2008 |month=April |pmid=18398080 |doi=10.1001/jama.299.14.1678 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=18398080 |issn=}}</ref> and a study of mixed [[primary prevention]] and [[secondary prevention]]<ref name="pmid18376000">{{cite journal |author=Kastelein JJ, Akdim F, Stroes ES, ''et al'' |title=Simvastatin with or without ezetimibe in familial hypercholesterolemia |journal=N. Engl. J. Med. |volume=358 |issue=14 |pages=1431–43 |year=2008 |month=April |pmid=18376000 |doi=10.1056/NEJMoa0800742 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=18376000&promo=ONFLNS19 |issn=}}</ref>. [[Niacin]] has been studied with improvements in the LDL and HDL<ref name="pmid17239888">{{cite journal |author=McKenney JM, Jones PH, Bays HE, ''et al'' |title=Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study) |journal=Atherosclerosis |volume=192 |issue=2 |pages=432–7 |year=2007 |month=June |pmid=17239888 |doi=10.1016/j.atherosclerosis.2006.11.037 |url=http://linkinghub.elsevier.com/retrieve/pii/S0021-9150(06)00733-7 |issn=}}</ref> with uncertain effects on [[carotid intima-media thickness]] <ref name="pmid15537681">{{cite journal |author=Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, Grace KA |title=Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins |journal=Circulation |volume=110 |issue=23 |pages=3512–7 |year=2004 |month=December |pmid=15537681 |doi=10.1161/01.CIR.0000148955.19792.8D |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=15537681 |issn=}}</ref>.


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Hypercolesterolemia is "a condition with abnormally high levels of cholesterol in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population."[1]

Treatment

Clinical practice guidelines by the National Institute for Health and Clinical Excellence recommend treatment if the estimated 10 year risk of cardiovascular disease is at least 20%.[2][3]

Primary prevention

One meta-analysis found that overall mortality is insignificantly reduced from 6.6% over 4.3 years to 6.1% in patients without prior cardiovascular disease (Number needed to treat, although statistically insignificant, is estimated to be 200).[4]

A second meta-analysis reported that statins can significantly help in the primary prevention of coronary heart disease among patients at risk.[5]

Combination treatment

It is not clear that combination therapy is better than high dose hydroxymethylglutaryl-coenzyme A reductase inhibitors.[6] If treatment with a hydroxymethylglutaryl-coenzyme A reductase inhibitor does not achieve a desirable cholesterol, other drugs that have been studied include eicosapentaenoic acid which is a metabolite of fish oil.[7] Ezetimibe, a cholesterol-absorption inhibitor, was not clearly beneficial in a study of diabetes mellitus type 2[8] and a study of mixed primary prevention and secondary prevention[9]. Niacin has been studied with improvements in the LDL and HDL[10] with uncertain effects on carotid intima-media thickness [11].

Secondary prevention

Clinical practice guidelines by the National Institute for Health and Clinical Excellence recommend treatment goal of <4 mmol/l (77 mg/dl)or a low density lipoprotein cholesterol concentration of <2 mmol/l (154 mg/dl).[2][3]

Combination treatment

If treatment with a hydroxymethylglutaryl-coenzyme A reductase inhibitor does not achieve a desirable cholesterol, other drugs that may be added for additional benefit include niacin[12][11] and fish oil. Ezetimibe, a cholesterol-absorption inhibitor, was not clearly beneficial in a study of diabetes mellitus type 2[8] and a study of mixed primary prevention and secondary prevention[9].

Diabetic patients

For more information, see: Diabetes_mellitus_type_2#Hypercholesterolemia.


Whether diabetes is an equivalent risk factor to having an existing myocardial infarction is debated.[13]

Statin therapy prevents major vascular events in about 1 of every 24 patients with diabetes who use the treatment for 5 years if they are similar to the patients in the meta-analysis by Kearney et al (Number needed to treat is 24).[14]

Treating to a goal of LDL-C < 70 mg/dl and systolic blood pressure to < 115 mm Hg may cause regression of carotid intima-media thickness in a randomized controlled trial.[15]

References

  1. ↑ Anonymous. Hypercholesterolemia. National Library of Medicine. Retrieved on 2008-01-18.
  2. ↑ 2.0 2.1 Cooper A, O'Flynn N (2008). "Risk assessment and lipid modification for primary and secondary prevention of cardiovascular disease: summary of NICE guidance". BMJ. PMID 18511800. PMC 2405875. [e]
  3. ↑ 3.0 3.1 Anonymous (2008). Lipid modification. National Institute for Health and Clinical Excellence. Retrieved on 2008-08-26.
  4. ↑ Thavendiranathan P, Bagai A, Brookhart MA, Choudhry NK (2006). "Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials". Arch. Intern. Med. 166 (21): 2307–13. DOI:10.1001/archinte.166.21.2307. PMID 17130382. Research Blogging.
  5. ↑ Brugts JJ, Yetgin T, Hoeks SE, et al. (2009). "The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials". BMJ 338: b2376. PMID 19567909. [e]
  6. ↑ Sharma M, Ansari MT, Abou-Setta AM, Soares-Weiser K, Ooi TC, Sears M et al. (2009). "Systematic review: comparative effectiveness and harms of combination therapy and monotherapy for dyslipidemia.". Ann Intern Med 151 (9): 622-30. DOI:10.1059/0003-4819-151-9-200911030-00144. PMID 19884623. Research Blogging.
  7. ↑ Yokoyama M, Origasa H, Matsuzaki M, et al (March 2007). "Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis". Lancet 369 (9567): 1090–8. DOI:10.1016/S0140-6736(07)60527-3. PMID 17398308. Research Blogging.
  8. ↑ 8.0 8.1 Howard BV, Roman MJ, Devereux RB, et al (April 2008). "Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes: the SANDS randomized trial". JAMA 299 (14): 1678–89. DOI:10.1001/jama.299.14.1678. PMID 18398080. Research Blogging.
  9. ↑ 9.0 9.1 Kastelein JJ, Akdim F, Stroes ES, et al (April 2008). "Simvastatin with or without ezetimibe in familial hypercholesterolemia". N. Engl. J. Med. 358 (14): 1431–43. DOI:10.1056/NEJMoa0800742. PMID 18376000. Research Blogging.
  10. ↑ McKenney JM, Jones PH, Bays HE, et al (June 2007). "Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study)". Atherosclerosis 192 (2): 432–7. DOI:10.1016/j.atherosclerosis.2006.11.037. PMID 17239888. Research Blogging.
  11. ↑ 11.0 11.1 Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, Grace KA (December 2004). "Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins". Circulation 110 (23): 3512–7. DOI:10.1161/01.CIR.0000148955.19792.8D. PMID 15537681. Research Blogging.
  12. ↑ Brown BG, Zhao XQ, Chait A, et al. (November 2001). "Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease". N. Engl. J. Med. 345 (22): 1583–92. PMID 11757504. [e]
  13. ↑ Bulugahapitiya U, Siyambalapitiya S, Sithole J, Idris I (February 2009). "Is diabetes a coronary risk equivalent? Systematic review and meta-analysis". Diabet. Med. 26 (2): 142–8. DOI:10.1111/j.1464-5491.2008.02640.x. PMID 19236616. Research Blogging.
  14. ↑ Kearney PM, Blackwell L, Collins R, et al (2008). "Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis". Lancet 371 (9607): 117–25. DOI:10.1016/S0140-6736(08)60104-X. PMID 18191683. Research Blogging.
  15. ↑ Howard, B. V., Roman, M. J., Devereux, R. B., Fleg, J. L., Galloway, J. M., Henderson, J. A., et al. (2008). Effect of Lower Targets for Blood Pressure and LDL Cholesterol on Atherosclerosis in Diabetes: The SANDS Randomized Trial. JAMA, 299(14), 1678-1689. DOI:10.1001/jama.299.14.1678.
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