29. Women also have a different baseline risk than men and therefore may not derive the same benefit. Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial. Dalcetrapib and anacetrapib are novel compounds in Phase III of clinical trials. Arnold, M.A.,Swanson, B.J.,Crowder, C.D.,Frankel, W.L.,Lam-Himlin, D.,Singhi, A.D.,Stanich, P.P.,Arnold, C.A. Brouwers, M. C.,VanGreevenbroek, M. M.,Stehouwer, C. D.,de Graaf, J.,Stalenhoef, A. F. Thegenetics of familial combined hyperlipidaemia. Petersen LK, Lack of benefit of dietary advice to men with angina: results of a controlled trial. Taylor AJ, The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. Morantz C, Therefore, niacin inhibits VLDL secretion, in turn decreasing production of LDL. 38. ‡—Changes in mean carotid intima-media thickness or proximal coronary artery stenosis. Narrative review: statin-related myopathy. Giral P. Fonseca FA, This elevation of plasma lipids is among the leading risk factors associated with cardiovascular diseases. Tiller R. Hanefeld M, 2010;170(12):1007–1008. ; Interventions in the management of serum lipids for preventing stroke recurrence. Majdan AA, Carlson, L.A. Nicotinic acid: the broad-spectrum lipid drug. Bomba E, Afilalo J, A Cochrane review concluded that statin use did not reduce mortality in patients with peripheral arterial disease.50 However, using statins in these patients increased maximal walking distance by 499 ft (152 m) and pain-free walking distance by 295 ft (90 m). Sharma M, Learn vocabulary, terms, and more with flashcards, games, and other study tools. 2008;51(1):37–45. 23. de Lorgeril M, Bis-(3-(4-nitrophenyl)prop-2-ene)disulfide, a new derivatives of diallyldisulfide,is effective in reducing plasma total cholesterol27. 3. Gastrointestinal disturbances are the most common complaints of the bile acid sequestrantsinclude constipation, nausea, indigestion,bloating and flatulence34. Moye LA, Jukema JW, Increase in HDL production and stimulation of reverse cholesterol transport. Omega 3 fatty acids for prevention and treatment of cardiovascular disease. et al. Bile acid sequestrants are positively charged resins that bind to the negatively charged bile acids in the intestine to form a large insoluble complex that not absorbed and so excreted in the feces. Eisenberg MJ. et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Kragstrup J. et al. Lescol Intervention Prevention Study (LIPS) Investigators. Cholesteryl ester transfer protein (CETP), also called plasma lipid transfer protein, is a hydrophobic plasma glycoprotein that accelerates the transferring of esterified cholesterol esters (CE) from HDLs to chylomicrons, VLDL and LDL, in exchange for triglyceride. The one study evaluating resins in patients with moderate risk (0.6 to 1.4 percent annual risk) did not show a clear mortality benefit.35. Santamarina-Fojo, S.,González-Navarro, H., Freeman, L., Wagner, E.,Nong, Z. Hepatic lipase, lipoprotein metabolism, and atherogenesis. Effects of combination lipid therapy in type 2 diabetes mellitus [published correction appears in. A systematic review concluded that lipid-lowering therapy in women does not change overall mortality, but may reduce the risk of coronary events in secondary, but not primary, prevention.55. Foote C, Eisenberg MJ. Lovato LC, Awan Z, Cochrane Database Syst Rev. Cholesterol lowering, cardiovascular diseases, and the rosuvastatin-JUPITER controversy: a critical reappraisal. Based on these findings, it is reasonable to initiate lower doses of statins in patients with stable CHD and reserve initial high-dose statins for those with recent acute coronary syndrome. Lancet. 8. For example, there is no evidence that fibrates have mortality benefit in primary prevention, and there is some evidence that they are harmful.11 None of the four trials that have compared fibrates with placebo in patients without a history of CHD showed that fibrates reduce overall mortality.27–30 In three of the trials, fibrates reduced the risk of coronary events compared with placebo (NNT = 125 with clofibrate [not available in the United States]; NNT = 72 with gemfibrozil [Lopid]; NNT = 8 with bezafibrate [not available in the United States]).27–29 Clofibrate was associated with an increased risk of overall mortality (number needed to harm [NNH] = 9 for 13.2 years).27 Combining fibrate with statin therapy does not appear to be beneficial.31, Niacin is the only drug consistently proven to raise HDL cholesterol levels32–34; however, there is no evidence that it reduces all-cause or cardiovascular mortality in primary prevention.7 In the JUPITER study, patients taking rosuvastatin had fewer CHD outcomes regardless of HDL cholesterol level.22 This implies that significantly lowering LDL cholesterol levels may be just as effective at protecting against CHD as artificially raising HDL cholesterol levels.22, When used in primary prevention, bile acid–binding resins (e.g., cholestyramine [Questran], colestipol [Colestid], colesevelam [Welchol]) reduce LDL cholesterol levels, but do not affect mortality.7 There are no studies of resin therapy to reduce CHD risk in patients at low risk (less than 0.6 percent annual risk) or at high risk (1.5 percent or greater annual risk) of a primary event. Cardiovascular disease (CVD) is the leading cause of mortality in the United States, accounting for 33.6 percent of all deaths in 2007.1 Hyperlipidemia is a common risk factor for CVD, with 53.4 percent of adults in the United States having abnormal cholesterol values and 32 percent having elevated low-density lipoprotein (LDL) cholesterol levels.1, Enlarge Many agents such as lanosterol synthase inhibitors, squalene epoxidase inhibitors, diacyl glycerol acyl transferase inhibitors, ATP citrate lyase inhibitors have shown a promising potential in the treatment of hyperlipidemia in clinical trials. In theory, when comparing the treat-to-target and fixed-dose approaches, essentially the same number of patients would be treated with statin therapy.5 A theoretical modeling study comparing approaches for primary CHD risk reduction suggests that a fixed-dose approach based on individual risk would prevent more events and save more quality-adjusted life-years.5 Although neither approach is clearly superior at this time, it is reasonable for physicians to engage patients in a shared, informed decision-making process and to determine treatment goals based on the patient's overall CHD risk, risk reduction that could be expected with treatment, and values and preferences. Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report Circulation. Brown BG, Frick MH, Zhao YT, Yang YH, Increased VLDL production and decreased excretion, Increased VLDL production and decreased LPL. Medications should be chosen based on a favorable balance between the likelihood of benefits (e.g., patient-oriented outcomes, mortality, CVD events, functional status, quality of life) and harm (adverse effects), as well as cost.6 Table 2 summarizes medications used to treat lipid disorders.7–20, Contraindicated in complete biliary or bowel obstruction, Constipation, nausea, and bloating are common, leading to poor adherence in most patients, May increase triglycerides; use with caution when triglyceride level is > 200 mg per dL (2.26 mmol per L), Combined primary/secondary prevention: reduces relative risk of cardiovascular mortality by 30 percent, Primarily reduces LDL cholesterol by 15 to 30 percent, Many drug interactions; separate from warfarin(Coumadin), digoxin, and amiodarone by at least two hours, Must be mixed with water or orange juice and taken before meals, No serious safety concerns with monotherapy, Well tolerated as monotherapy; side effect profile similar to placebo, Arthralgias and myalgias more common when combined with a statin 9,10, Lacks clinical outcome data (monotherapy or combined with a statin), Monotherapy reduces LDL cholesterol by 18 percent, May increase likelihood of attaining LDL cholesterol goals when combined with a statin, No known effect on absorption of other medications, Contraindicated in active liver disease when combined with a statin (e.g., Vytorin), Contraindicated in severe hepatic or renal disease, Gastrointestinal upset, rash, and abdominal pain are common, Decreased renal function and myopathies are rare, Increases risk of gallstones by 1 to 2 percent, Combined primary/secondary prevention: NNT = 46 to 125 to prevent one coronary event; NNT = 53 to 150 to prevent one nonfatal myocardial infarction, Multiple prescription preparations (fenofibrate) $$$, Gemfibrozil taken twice daily before meals, Micronized fenofibrate tablets and capsules should be taken with food, HMG-CoA reductase inhibitors (statins)7,14–18, Contraindicated in active liver disease and pregnancy, Generally better tolerated than other agents, Myopathies occur in less than 1 percent of patients; increased incidence when used with fibrates, Rhabdomyolysis occurs in less than 0.2 percent of patients, Liver function test results greater than three times the upper limit of normal occur in less than 2 percent of patients, Primary prevention: NNT = 81 for four years to prevent one coronary event; NNT = 244 for four years to prevent one cerebrovascular event, Secondary prevention: NNT = 50 for five years to prevent one death, Acute coronary syndrome: NNT = 77 treated with high-dose statins for two years to prevent one death, Fluvastatin, lovastatin, pravastatin, and simvastatin should be taken in the evening, Contraindicated in severe peptic ulcer disease, chronic liver disease, and severe gout, Flushing is common; may be reduced with aspirin pretreatment, May increase uric acid and glucose levels, When combined with statins, improves disease-oriented outcomes‡, Primarily increases HDL cholesterol by 15 to 35 percent, Multiple OTC preparations (immediate or controlled release) $, Multiple prescription preparations (controlled release) $$$$, OTC preparations may be less effective, but have fewer adverse effects, Use with caution in patients with fish allergy, Dyspepsia, burping, and fishy taste most common, Secondary prevention: NNT = 57 for two years to prevent one death in patients with previous myocardial infarction; NNH = 159 for two years resulting in one sudden cardiac death in patients with angina, Four prescription capsules taken once or twice daily, OTC preparations may require multiple capsules to achieve doses used in clinical trials. 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