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• W2000817738 abstract "Dyslipidemia is one of the most important modifiable risk factors for coronary disease. Despite the availability of highly effective lipid-modifying agents, many patients still do not reach lipid targets established by national guidelines. Niacin has been known to be an effective treatment of dyslipidemia for almost half a century. Niacin substantially increases high-density lipoprotein cholesterol (HDL-C) levels while lowering levels of low-density lipoprotein cholesterol (LDL-C), triglycerides, and lipoprotein(a). In addition, niacin converts small LDL particles into more buoyant, less atherogenic LDL particles. Combined with other agents, niacin offers an important treatment option for patients with dyslipidemia. In particular, niacin complements LDL-C-lowering drugs; it is the most effective agent available for increasing HDL-C levels while lowering levels of LDL-C and triglycerides and improving other lipid risk factors such as lipoprotein(a). Combining niacin with statins or bile acid sequestrant therapy is safe and effective for improving lipid levels and decreasing coronary risk. Differences in niacin formulations dictate tolerability profiles and should be considered when selecting niacin as part of lipid therapy. Furthermore, adverse effects on glucose and insulin sensitivity should be considered when selecting candidates for niacin therapy. Adding niacin to lipid-lowering regimens is a valuable option for physicians treating patients with dyslipidemia and should be considered in appropriate patients. Dyslipidemia is one of the most important modifiable risk factors for coronary disease. Despite the availability of highly effective lipid-modifying agents, many patients still do not reach lipid targets established by national guidelines. Niacin has been known to be an effective treatment of dyslipidemia for almost half a century. Niacin substantially increases high-density lipoprotein cholesterol (HDL-C) levels while lowering levels of low-density lipoprotein cholesterol (LDL-C), triglycerides, and lipoprotein(a). In addition, niacin converts small LDL particles into more buoyant, less atherogenic LDL particles. Combined with other agents, niacin offers an important treatment option for patients with dyslipidemia. In particular, niacin complements LDL-C-lowering drugs; it is the most effective agent available for increasing HDL-C levels while lowering levels of LDL-C and triglycerides and improving other lipid risk factors such as lipoprotein(a). Combining niacin with statins or bile acid sequestrant therapy is safe and effective for improving lipid levels and decreasing coronary risk. Differences in niacin formulations dictate tolerability profiles and should be considered when selecting niacin as part of lipid therapy. Furthermore, adverse effects on glucose and insulin sensitivity should be considered when selecting candidates for niacin therapy. Adding niacin to lipid-lowering regimens is a valuable option for physicians treating patients with dyslipidemia and should be considered in appropriate patients. Coronary heart disease (CHD) is the single largest cause of death in American men and women, and dyslipidemia is one of the major modifiable risk factors.1National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) 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. 2002; 106: 3143-3421PubMed Google Scholar Despite efforts by the medical and public health communities to increase awareness of the risks of dyslipidemia and encourage lipid screening, patients often are inadequately treated, and less than 40% reach National Cholesterol Education Program (NCEP) low-density lipoprotein cholesterol (LDL-C) targets with monotherapy.2Pearson TA Laurora I Chu H Kafonek S The Lipid Treatment Assessment Project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals.Arch Intern Med. 2000; 160: 459-467Crossref PubMed Scopus (1009) Google Scholar Furthermore, risk assessment limited to LDL-C fails to identify a substantial number of patients at risk for coronary events. Most patients with CHD have multiple lipid abnormalities, ie, mixed dyslipidemia. The Veterans Affairs HDL Intervention Trial (VA-HIT) group3Rubins HB Robins SJ Collins D Department of Veterans Affairs HDL Intervention Trial Study Group et al.Distribution of lipids in 8,500 men with coronary artery disease.Am J Cardiol. 1995; 75: 1196-1201Abstract Full Text PDF PubMed Scopus (211) Google Scholar found that 87% of 8500 patients with established CHD had suboptimal LDL-C levels (=100 mg/dL), and 33% had hypertriglyceridemia (triglyceride [TG] levels >200 mg/dL). In addition, approximately 60% of the study population had low levels of high-density lipoprotein cholesterol (HDL-C) (=40 mg/dL). Because of its effects on all components of the lipid profile, niacin has gained attention as an important therapeutic option for patients with multiple lipid abnormalities and for those not achieving treatment targets while receiving monotherapy. This article discusses (1) the importance of measuring and improving lipoprotein levels other than LDL-C to reduce coronary risk and (2) the role of niacin as both monotherapy and in combination with other lipidmodifying agents in the treatment of dyslipidemia. The importance of improving the overall lipid profile is becoming increasingly understood. The NCEP III has identified non-HDL-C, the sum of all atherogenic lipoproteins, as a secondary target of therapy for patients with TG levels of 200 mg/dL or higher.1National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) 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. 2002; 106: 3143-3421PubMed Google Scholar Non-HDL-C, calculated by subtracting the HDL-C value from the total cholesterol (TC) value, is considered a predictor of CHD risk. The new guidelines emphasize that, although LDL-C remains the primary target of therapy, once goals have been achieved, focus must turn to other lipid abnormalities. Low levels of HDL-C are strong independent predictors of CHD risk. Each 1 mg/dL increase in HDL-C is associated with a 2% to 3% decrease in CHD risk, even after adjustment for other risk factors, and predicts coronary risk regardless of LDL-C levels.4Castelli WP Cholesterol and lipids in the risk of coronary artery disease—the Framingham Heart Study.Can J Cardiol. 1988; 4: 5A-10APubMed Google Scholar The NCEP III has identified HDL-C levels less than 40 mg/dL as a risk factor for CHD, although no goal has been set.1National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) 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. 2002; 106: 3143-3421PubMed Google Scholar In a recently published editorial, Sacks et al,5Sacks FM Expert Group on HDL Cholesterol The role of high-density lipoprotein (HDL) cholesterol in the prevention and treatment of coronary heart disease: expert group recommendations [editorial].Am J Cardiol. 2002; 90: 139-143Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar on the basis of current clinical research, proposed an HDL-C goal of 40 mg/dL or higher in patients with, or at high risk for, CHD. Recent research also stresses the importance of elevated TG levels as an independent risk factor for CHD events. The VA-HIT was the first trial to show that improvements in levels of HDL-C (6% increase) and TG (31% decrease) with gemfibrozil, without substantial reductions in LDL-C levels, decreased CHD death, nonfatal myocardial infarction (MI), and stroke by 24%.6Rubins HB Robins SJ Collins D Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group et al.Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol.N Engl J Med. 1999; 341: 410-418Crossref PubMed Scopus (3180) Google Scholar The NCEP identifies TG levels of less than 150 mg/dL as optimal and recommends treatment for TG levels of 200 mg/dL or higher.1National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) 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. 2002; 106: 3143-3421PubMed Google Scholar Lipoprotein(a) [Lp(a)] is a modified form of LDL with a distinctive glycoprotein [apo(a)] that shares structural homology with plasminogen; consequently, increased levels of Lp(a) may impair fibrinolysis, thereby increasing plaque development and thrombotic events.7Danesh J Collins R Peto R Lipoprotein(a) and coronary heart disease: meta-analysis of prospective studies.Circulation. 2000; 102: 1082-1085Crossref PubMed Scopus (814) Google Scholar To date, no data show that lowering Lp(a) levels leads to clinical benefit; however, a meta-analysis of 27 prospective studies showed that, although Lp(a) levels were not correlated with other classic CHD risk factors, they were associated with CHD risk. Patients with Lp(a) levels in the highest tertile had an approximate 70% increase in CHD risk over patients with Lp(a) levels in the lowest tertile.7Danesh J Collins R Peto R Lipoprotein(a) and coronary heart disease: meta-analysis of prospective studies.Circulation. 2000; 102: 1082-1085Crossref PubMed Scopus (814) Google Scholar Both the LDL-C/HDL-C ratio and the TC/HDL-C ratio predict CHD risk. However, the LDL-C/HDL-C ratio may underestimate the degree of CHD risk in some patients.8Lemieux I Lamarche B Couillard C et al.Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study.Arch Intern Med. 2001; 161: 2685-2692Crossref PubMed Scopus (370) Google Scholar Investigators from the Quebec Cardiovascular Study8Lemieux I Lamarche B Couillard C et al.Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study.Arch Intern Med. 2001; 161: 2685-2692Crossref PubMed Scopus (370) Google Scholar reported that variations in the TC/HDL-C ratio might be more predictive of CHD risk than the LDL-C/HDL-C ratio (Figure 1). This may be because there is more cholesterol in the very low-density lipoprotein (VLDL) fraction in patients with hypertriglyceridemia than in the LDL-C component.8Lemieux I Lamarche B Couillard C et al.Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study.Arch Intern Med. 2001; 161: 2685-2692Crossref PubMed Scopus (370) Google Scholar In the 6 clinical end point trials that used statin therapy,9Downs 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: 1615-1622Crossref PubMed Scopus (4995) Google Scholar, 10Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).Lancet. 1994; 344: 1383-1389Abstract PubMed Scopus (4) Google Scholar, 11Sacks FM Pfeffer MA Moye LA Cholesterol and Recurrent Events Trial Investigators et al.The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels.N Engl J Med. 1996; 335: 1001-1009Crossref PubMed Scopus (7191) Google Scholar, 12Shepherd J Cobbe SM Ford I West of Scotland Coronary Prevention Study Group et al.Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia.N Engl J Med. 1995; 333: 1301-1307Crossref PubMed Scopus (7469) Google Scholar, 13Long-Term Intervention with Pravastatin in Ischaemic Disease (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: 1349-1357Crossref PubMed Scopus (5567) Google Scholar, 14Heart Protection Study Collaborative GroupMRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.Lancet. 2002; 360: 7-22Abstract Full Text Full Text PDF PubMed Scopus (7643) Google Scholar significant reduction in the TC/HDL-C ratio (Figure 2) coincided with clinical event reduction, ranging between 25% and 35%.Figure 2Changes in total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio in major statin trials.9Downs 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: 1615-1622Crossref PubMed Scopus (4995) Google Scholar, 10Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).Lancet. 1994; 344: 1383-1389Abstract PubMed Scopus (4) Google Scholar, 11Sacks FM Pfeffer MA Moye LA Cholesterol and Recurrent Events Trial Investigators et al.The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels.N Engl J Med. 1996; 335: 1001-1009Crossref PubMed Scopus (7191) Google Scholar, 12Shepherd J Cobbe SM Ford I West of Scotland Coronary Prevention Study Group et al.Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia.N Engl J Med. 1995; 333: 1301-1307Crossref PubMed Scopus (7469) Google Scholar, 13Long-Term Intervention with Pravastatin in Ischaemic Disease (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: 1349-1357Crossref PubMed Scopus (5567) Google Scholar, 14Heart Protection Study Collaborative GroupMRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.Lancet. 2002; 360: 7-22Abstract Full Text Full Text PDF PubMed Scopus (7643) Google Scholar 4S = Scandinavian Simvastatin Survival Study; AFCAPS = Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS); CARE = Cholesterol and Recurrent Events trial; HPS = MRC/BHF [Medical Research Council/British Heart Foundation] Heart Protection Study; LIPID = Long-term Intervention with Pravastatin in Ischaemic Disease; WOSCOPS = West of Scotland Coronary Prevention Study.View Large Image Figure ViewerDownload (PPT) Although the exact mechanism is complex and not understood completely, the likely primary action of niacin is to inhibit mobilization of free fatty acids from peripheral adipose tissue to the liver. Consequently, niacin reduces hepatic synthesis of VLDL and TG. Because less VLDL is available as a substrate, LDL-C levels decrease.15Piepho RW The pharmacokinetics and pharmacodynamics of agents proven to raise high-density lipoprotein cholesterol.Am J Cardiol. 2000; 86: 35L-40LAbstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar Niacin is believed to increase serum HDL-C levels by blocking hepatic uptake of apolipoprotein A-I, a major component of HDL-C.15Piepho RW The pharmacokinetics and pharmacodynamics of agents proven to raise high-density lipoprotein cholesterol.Am J Cardiol. 2000; 86: 35L-40LAbstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar Niacin also increases a cardioprotective subfraction of HDL, which enhances reverse cholesterol transport.16Sakai T Kamanna VS Kashyap ML Niacin, but not gemfibrozil, selectively increases LP-AI, a cardioprotective subfraction of HDL, in patients with low HDL cholesterol.Arterioscler Thromb Vasc Biol. 2001; 21: 1783-1789Crossref PubMed Scopus (107) Google Scholar Niacin decreases levels of LDL-C by 5% to 25%, TG by 20% to 50%, Lp(a) by 34%,17Carlson LA Hamsten A Asplund A Pronounced lowering of serum levels of lipoprotein Lp(a) in hyperlipidaemic subjects treated with nicotinic acid.J Intern Med. 1989; 226: 271-276Crossref PubMed Scopus (396) Google Scholar and the TC/HDL-C ratio by 27%18Luria MH Effect of low-dose niacin on high-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein cholesterol ratio.Arch Intern Med. 1988; 148: 2493-2495Crossref PubMed Scopus (49) Google Scholar; niacin increases levels of HDL-C by 15% to 35%.1National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) 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. 2002; 106: 3143-3421PubMed Google Scholar The Coronary Drug Project19Clofibrate and niacin in coronary heart disease.JAMA. 1975; 231: 360-381Crossref PubMed Scopus (1509) Google Scholar was the first trial to study the effect of niacin on cardiovascular end points. After 6 years, treatment with niacin reduced the incidence of nonfatal MI by 26% and cerebrovascular events by 24%. Total mortality was not significantly reduced in the original trial; however, about 9 years after trial termination, the group originally treated with niacin had 11% fewer deaths than did the placebo group (P<.001).20Canner PL Berge KG Wenger NK et al.Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin.J Am Coll Cardiol. 1986; 8: 1245-1255Abstract Full Text PDF PubMed Scopus (1593) Google Scholar It has been hypothesized that the mortality benefit reflects the early effect of niacin on reducing nonfatal cardiovascular events. In the Stockholm Ischaemic Heart Disease Secondary Prevention Study,21Carlson 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: 405-418Crossref PubMed Scopus (596) Google Scholar combination therapy with immediate-release niacin and clofibrate reduced levels of TC by 13% and TG by 19%. Total mortality and CHD mortality were significantly reduced by 26% (P<.05) and 36% (P<.01), respectively, with combination therapy. Despite the benefits of niacin therapy, cutaneous flushing has limited its use. Facial and truncal flushing occur in most patients, leading to discontinuation of niacin in up to 25% of patients in studies,22Knopp RH Ginsberg J Albers JJ et al.Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin.Metabolism. 1985; 34: 642-650Abstract Full Text PDF PubMed Scopus (216) Google Scholar, 23McKenney JM Proctor JD Harris S Chinchili VM A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients.JAMA. 1994; 271: 672-677Crossref PubMed Scopus (290) Google Scholar, 24Stein EA Davidson MH Dujovne CA et al.Efficacy and tolerability of low-dose simvastatin and niacin, alone and in combination, in patients with combined hyperlipidemia: a prospective trial.J Cardiovasc Pharmacol Ther. 1996; 1: 107-116PubMed Google Scholar although these rates are likely to be higher in general practice. Tolerance to the flushing effects of niacin frequently develops with continued use; however, many patients discontinue therapy before this can develop. Several steps can be taken to decrease the severity of flushing and increase patient compliance. First, the patient should be counseled about the importance of continuing therapy and be reminded that interruptions in therapy may diminish any tolerance that has developed. Aspirin (325 mg) or a nonsteroidal anti-inflammatory medication such as ibuprofen (200 mg) taken 30 minutes to 1 hour before the first niacin dose of the day decreases the severity of flushing.25Wilkin JK Wilkin O Kapp R Donachie R Chernosky ME Buckner J Aspirin blocks nicotinic acid-induced flushing.Clin Pharmacol Ther. 1982; 31: 478-482Crossref PubMed Scopus (73) Google Scholar Other precautionary steps include slowly titrating the dose of niacin upward, taking the niacin dose with food, and avoiding spicy foods, hot beverages, and/or hot showers close to taking a dose.15Piepho RW The pharmacokinetics and pharmacodynamics of agents proven to raise high-density lipoprotein cholesterol.Am J Cardiol. 2000; 86: 35L-40LAbstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar Sustained-release formulations of niacin were developed to minimize flushing. Sustained-release niacin is available over the counter as a dietary supplement. In a retrospective study of 63 patients treated with sustained-release niacin, HDL-C levels increased by 18%, and the TC/HDL-C ratio and levels of TC, LDL-C, and TG decreased by 25%, 9%, 13%, and 20%, respectively. The investigators noted a wide range of responses among participants; the changes in HDL-C levels ranged from −5% to 35%, which were not correlated with niacin dose.26Squires RW Allison TG Gau GT Miller TD Kottke BA Low-dose, time-release nicotinic acid: effects in selected patients with low concentrations of high-density lipoprotein cholesterol.Mayo Clin Proc. 1992; 67: 855-860Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar Another study showed similar efficacy, including a subgroup of patients with isolated low HDL-C levels, and more marked effects were noted in another subgroup of patients with hypertriglyceridemia.27Lavie CJ Mailander L Milani RV Marked benefit with sustained-release niacin therapy in patients with “isolated” very low levels of high-density lipoprotein cholesterol and coronary artery disease.Am J Cardiol. 1992; 69: 1083-1085Abstract Full Text PDF PubMed Scopus (55) Google Scholar However, some sustained-release niacin preparations are associated with an increased incidence and severity of hepatotoxicity.23McKenney JM Proctor JD Harris S Chinchili VM A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients.JAMA. 1994; 271: 672-677Crossref PubMed Scopus (290) Google Scholar, 28Dalton TA Berry RS Hepatotoxicity associated with sustained-release niacin.Am J Med. 1992; 93: 102-104Abstract Full Text PDF PubMed Scopus (82) Google Scholar In a comparative study of 46 adults treated with sequential doses of sustained-release or immediate-release niacin, 52% of patients treated with the sustained-release form exhibited hepatotoxicity. Of these patients, 67% withdrew prematurely because of elevated levels of hepatic enzymes.23McKenney JM Proctor JD Harris S Chinchili VM A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients.JAMA. 1994; 271: 672-677Crossref PubMed Scopus (290) Google Scholar The rate of hepatotoxicity appears to differ among products. In the study by Lavie et al,27Lavie CJ Mailander L Milani RV Marked benefit with sustained-release niacin therapy in patients with “isolated” very low levels of high-density lipoprotein cholesterol and coronary artery disease.Am J Cardiol. 1992; 69: 1083-1085Abstract Full Text PDF PubMed Scopus (55) Google Scholar only 1 of 36 patients (3%) discontinued sustained-release niacin therapy because of elevated levels of hepatic enzymes. Therefore, patients should be treated with only 1 brand of niacin and should not be switched from immediate-release to sustained-release niacin. If switching is necessary because of intolerance, the dose and dosing schedule should be adjusted by the physician and again titrated upward. Niacin can be used safely with proper physician supervision and monitoring; it is probably most important to counsel the patient not to self-treat or change prescribed therapy unless instructed to do so by the physician.29Parsons Jr, WB Cholesterol Control Without Diet! The Niacin Solution. Lilac Press, Scottsdale, Ariz1998Google Scholar The major adverse effects of the various niacin preparations are related to their metabolism and dissolution rate. Niacin is metabolized by 2 processes: (1) a low-affinity, high-capacity pathway in which the drug is conjugated with glycine to form nicotinuric acid and (2) a high-affinity, low-capacity pathway whereby the drug undergoes a series of oxidation-reduction reactions that yield nicotinamide and pyrimidines.15Piepho RW The pharmacokinetics and pharmacodynamics of agents proven to raise high-density lipoprotein cholesterol.Am J Cardiol. 2000; 86: 35L-40LAbstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar The conjugative pathway is associated with flushing, whereas the nonconjugative pathway is associated with hepatotoxicity. Immediate-release products quickly saturate the nonconjugative pathway, resulting in a large fraction being metabolized by the conjugative pathway, whereas the nonconjugative pathway mainly metabolizes the sustained-release products. Extended-release (ER) niacin is a Food and Drug Administration-approved intermediate-release preparation given once daily at bedtime. Extended-release niacin has been formulated to distribute drug absorption over 8 to 12 hours to balance metabolism between the 2 metabolic pathways. Its efficacy is comparable to that of immediate-release niacin; however, ER niacin is associated with a lower incidence of flushing than is immediate-release niacin and has a lower risk of hepatotoxicity than does sustained-release niacin.30Knopp RH Alagona 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: 1097-1104Abstract Full Text PDF PubMed Scopus (209) Google Scholar In a study of 223 patients treated with ER niacin or immediate-release niacin,30Knopp RH Alagona 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: 1097-1104Abstract Full Text PDF PubMed Scopus (209) Google Scholar LDL-C levels decreased, respectively, by 12% and 12%, TG levels by 16% and 18%, and Lp(a) levels by 15% and 11%; HDL-C levels increased by 20% and 17%, respectively (all P=.05). Patients treated with ER niacin experienced a lower incidence of flushing (P<.001); aspartate aminotransferase levels increased by 5% and 4.8% (difference between groups not significant) in ER niacin and immediate-release groups, respectively.30Knopp RH Alagona 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: 1097-1104Abstract Full Text PDF PubMed Scopus (209) Google Scholar In addition to flushing and hepatotoxicity, niacin has been associated with gastrointestinal (GI) complaints, including nausea, vomiting, diarrhea, and abdominal pain; activation of peptic ulcer disease; hyperuricemia and gout; hyperglycemia; and acanthosis nigricans.31Capuzzi DM Morgan JM Brusco Jr, OA Intenzo CM Niacin dosing: relationship to benefits and adverse effects.Curr Atheroscler Rep. 2000; 2: 64-71Crossref PubMed Scopus (80) Google Scholar, 32American Society of Health-System Pharmacists ASHP Therapeutic Position Statement on the safe use of niacin in the management of dyslipidemias.Am J Health Syst Pharm. 1997; 54: 2815-2819PubMed Google Scholar, 33Niaspan [prescribing information].in: Physicians' Desk Reference. 56th ed. Medical Economics Co, Inc, Montvale, NJ2002: 1846-1850Google Scholar Niacin therapy should be avoided in patients with active peptic ulcer disease, hepatic insufficiency or a history of liver disease, or recent history of acute gout.32American Society of Health-System Pharmacists ASHP Therapeutic Position Statement on the safe use of niacin in the management of dyslipidemias.Am J Health Syst Pharm. 1997; 54: 2815-2819PubMed Google Scholar The hyperglycemic effects of niacin are discussed in the section “Selecting Patients for Niacin Combination Therapy.” Bile acid sequestrants (BASs) offer a therapeutic option for patients with elevated LDL-C refractory to statin therapy or for patients who are intolerant of statin therapy. The major effect of BASs is to lower LDL-C levels (approximately 15%-30%); however, BASs have only a minor impact on HDL-C levels (3%-5%) and either no effect or a tendency to increase TG levels-a concern for patients with borderline or high TG levels.1National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment P" @default.
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• W2000817738 title "Niacin as a Component of Combination Therapy for Dyslipidemia" @default.
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