Abstract
Effective treatment of dyslipidemia improves prognosis. Statin therapy has been documented to decrease the cardiovascular event rate in the setting of elevated low-density lipoprotein (LDL) cholesterol levels and coronary heart disease, but most patients are not treated to the target (LDL ≤100 mg/dL) set by the National Cholesterol Education Program. The triglyceride level is also being increasingly recognized as an important mediator in the process of progressive atherosclerosis and cardiovascular events. Studies suggest the target level for triglycerides should be the same as for LDL cholesterol levels— no more than 100 mg/dL. In order to achieve these LDL and triglyceride levels, combination therapy is required frequently. Probably the most effective combination for mixed dyslipidemia is a statin with niacin. The use of adjunctive omega-3 supplementation also should be considered especially for patients with elevated triglyceride levels. Other adjunctive agents including sitostanol ester (in the form of a margarine) and a well-tolerated second generation bile acid sequestrant that will lower LDL cholesterol an additional 10% to 18% and will be available soon.
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References
LIPID Study Group: Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998, 339:1349–1357.
Scandinavian Simvastatin Survival Study Group: Baseline serum cholesterol and treatment effect in the Scandinavian Simvastatin Survival Study (4S). Lancet 1995, 345:1274–1275.
Shepard J, Cobbe SM, Ford I, et al.: Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995, 333:1301–1307.
Downs Jr, Clearfield M, Weis S, et al.: Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA 1998, 279:1615–1622.
Sacks FM, Pfeffer MA, Moye LA, et al.: The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996, 335:1001–1009.
National Cholesterol Education Program. Second report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). Circulation 1994, 89:1329–1445.
Hoerger TJ, Bala Mohan, Bray JW, et al.: Treatment patterns and distribution of low-density lipoprotein cholesterol levels in treatment-eligible United States adults. Am J Cardiol. 1998, 82:61–65.
The Post Coronary Artery Bypass Graft Trial Investigators: The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anti-coagulation on obstructive changes in saphenous-vein coronary artery bypass grafts. N Engl J Med 1997, 336:153–62.
Brown AS, Anderson TJ, Pitt B, et al.: AVERT Study: Oral Presentation. November 11, 1998. American Heart Association Annual Scientific Sessions. JAMA August 1999, in press.
Jones P, Kafonek S, Laurora I, et al.: Comarative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). Am J Cardiol 1998, 81:582–587.
O’Keefe JH, Miles JM, Harris WH, et al.: Improving the adverse cardiovascular prognosis of Type 2 diabetes. Mayo Clin Proc 1999, 74:171–180.
Jeppesen J, Ole Hein H, Suadicani P, et al.: Triglyceride concentration and ischemic heart disease: An eight year follow-up in the Copenhagen Male Study. Circulation 1998, 97:1029–1036.
Miller M, Sideler A, Moealemi A, et al.: Normal trigylceride levels and coronary artery disease events: The Baltimore Coronary Observational Long-Term Study. JACC 1998, 31:1252–1257.
Gaziano JM, Hennekens CH, O’Donnell CJ, et al.: Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction. Circulation. 1997, 96:2520–2525.
O’Keefe JH, Harris WS, Nelson J, et al.: Effects of pravastatin with niacin or magnesium on lipid levels and postprandial lipemia. Am J Cardiol. 1995, 76:480–484.
Davignon J, Roederer G, Montigny M, et al.: Comparative efficacy and safety of pravastatin, nicotinic acid and the two combined in patients with hypercholesterolemia. Am J Cardiol 1994, 73:339–345.
Gardner SF, Marx MA, White LM, et al.: Combination of low-dose niacin and pravastatin improves the lipid profile in diabetic patients without compromising glycemic control. Ann Pharmacother 1997, 31:677–682.
Gardner SF, Schneider EF, Granberry MC, et al.: Combination therapy with low-dose lovastatin and niacin is as effective as higher-dose lovastatin. Pharmacotherapy 1996, 16:419–423.
Tsalamandris C, Panagiotopoulos S, Sinha A, et al.: Complementary effects of pravastatin and nicotonic acid in the treatment of combined hyperlipidemia in diabetic and nondiabetic patients. J Cardiovasc Risk 1994, 1:231–239.
Reaven P, Witztum JL: Lovastatin, nicotinic acid, and rhabdomyolysis. Anna Intern Med 1988, October: 597–598.
McKenney JM, Proctor JD, Harris S, et al.: A comparison of the efficacy and toxic effects of sustained vs. immediate-release niacin in hypercholesterolemic patients. JAMA 1994, 271:672–677.
Knopp RH, Alogona P, Davidson M, et al.: Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia. Metabolism 1998, 47:1097–1104.
Guyton JR, Goldberg AC, Kreisberg RA, et al.: Effectiveness of once-nightly dosing of extended-release niacin alone and in combination for hypercholesteremia. Am J Cardiol 1998, 82:737–743.
Canner PL, Berge K, Wenger NK, et al.: Fifteen year mortality in coronary drug project patients: long-term benefit with niacin. J Am Coll Cardiol 1986, 8:1245–1255.
Cardlson LA, Rosenhamer G: Reduction of mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by combined treatment with clofibrate and nicotinic acid. Acta Med Scand 1988, 223:405–418.
Brown BG, Sacco D, Zhao X-Q, et al.: Lipid-lowering and plaque regression: new insights into prevention of plaque disruption and clinical events in coronary disease. Circulation 1993, 87:1781–1791.
O’Keefe JH, Harris WS: Nicotinic acid-the underused ally in the fight against coronary disease. J Cardiovasc Risk 1997, 4:161–163.
Miller M, Vogel RA: The practice of coronary disease prevention. In Total and Low-Density Lipoprotein Cholesterol. Edited by Retford DC, Kiehne Hayes LA; Philadelphia: William and Wilkins; 1996:50–52.
GelTex Pharmaceuticals, Inc.: Cholestagel. March 15, 1999, in press.
Schetman G, Hiatt J, Hartz A: Evaluation of the effectiveness of lipid-lowering therapy (bile acid sequestrants, niacin, psyllium and lovastatin) for treating hypercholesterolemia in veterans. Am J Card 1993, 71:759–765.
Frick MH, Elo O, Haapa K, et al.: Helsinki Heart Study: Primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia: safety of treatment, changes in risk-factors, and incidence of coronary heart disease. N Engl J Med 1987, 317:1237–1245.
Gould AL, Rossouq JE, Santanello NC, et al.: Cholesterol reduction yields clinical benefit. Circulation 1995, 91:2274–2282.
Glueck CJ, Oakes N, Speirs J, et al.: Gemfibrozil-lovastatin therapy for primary hyperlipoproteinemias. Am J Cardiol 1992, 70:1–9.
Pierce LR, Wysowski DK, Gross TP: Myocpathy and rhabdomyalysis assoicated with lovastatin-gemfibrozil combination therapy. JAMA 1990, 264:71–5.
Albert CM, Hennekens CH, O’Donnell CJ, et al.: Fish consumption and risk of sudden cardiac death. JAMA 1998, 279:23–28.
Siscovick DS, Raghunathan TE, King I, et al.: Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. JAMA 1995, 274:1363–1367.
Marchioli R: Efficacy of n-3 PUFA and vitamin E in 11,324 post-MI patients: Results of GISSI-Prevenzione. Lancet 1999, in press.
Harris WS: n-3 Fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 1997, 65 (suppl):1645–1654.
Nordoy A, Bonaa KH, Nilsen H, et al.: Effects of simvastatin and omega-3 fatty acids in plasma lipoproteins and lipid peroxidation in patiens with combined hyperlipidaemia. J Int Med 1998, 243:163–170.
Contacos C, Barter PJ, Sullivan DR: Effect of pravastatin and w-3 fatty acids on plasma lipids and lipoproteins in patients with combined hyperlipidemia. Arterioscler Thromb 1993, 13:1755–1762.
Hansen JB, Lyngmo V, Svensson B, et al.: Inhibition of exercise-induced shortening of bleeding time by fish oil in familial hypercholesterolemia. Arterioscler Thromb 1993, 1:98–104.
Miettinen TA, Puska P, Gylling H, et al.: Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. N Engl J Med. 1995, 333:1308–1312.
Gylling H, Miettinen TA: Sitostanol ester added to long-term simvastatin treatment of coronary patients with low and high basal cholesterol absorption. J Am Coll Cardiol 1998, 31 (Suppl):281.
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Alaswad, K., O’Keefe, J.H. & Moe, R.M. Combination drug therapy for dyslipidemia. Curr Atheroscler Rep 1, 44–49 (1999). https://doi.org/10.1007/s11883-999-0049-z
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DOI: https://doi.org/10.1007/s11883-999-0049-z