Wednesday, March 18, 2009
statines triglycerides
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Ask the Experts about Triglycerides in Cardiovascular Disease
What Are the Effects of Statins on Triglycerides and What Are the Results of Major Outcomes Studies?
Michael Miller, MD, FACC, FAHA
Medscape Family Medicine. 2009; ©2009 Medscape
Posted 03/12/2009
Question
What are the effects of statins on triglycerides and what are the results of major outcomes studies?
Response from Michael Miller, MD, FACC, FAHA
Associate Professor of Medicine, Epidemiology, and Preventive Medicine; Director, Center for Preventive Cardiology, Division of Cardiology, University of Maryland Medical Center, Baltimore, Maryland
Although the most prominent effects attributable to statin therapy are its potent low-density lipoprotein cholesterol (LDL-C) lowering properties, it is also well established that statins significantly reduce non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides (TG), and biomarkers of inflammation, most notably C-reactive protein (CRP). Overall, statins reduce TG levels in the range of 10% to 20% ( Table ), although it has been acknowledged that the higher the baseline TG level, the greater the TG-lowering effect. For example, baseline TG levels exceeding 250 mg/dL have been associated with reductions in the range of 22% to 45%, whereas more modest reductions have been observed with lower baseline levels.[1] This can be best identified in randomized, placebo-controlled trials ( Table ). In these outcome studies, the TG cutpoint for study exclusion has generally been 350 mg/dL to 400 mg/dL because higher levels have been viewed as a basis for pharmacologic (eg, nonstatin) treatment. Therefore, it is not surprising that, with few exceptions, the baseline TG in clinical outcome trials that evaluate statin therapy is customarily in the 100 to 200 mg/dL range, with a corresponding TG-lowering effect between 10% and 20%.[2-11] Although no relationship was observed between major coronary heart disease (CHD) events and on-treatment TG in one clinical trial of patients with CHD and high LDL-C,[12] another trial in patients with acute coronary syndrome demonstrated that lower on-treatment TG correlated with reduced CHD events.[13] Therefore, ongoing and future clinical trials will provide additional insight into the relationship between statin (monotherapy and/or combination) therapy, TG lowering, and CHD risk.
This activity is supported by an independent educational grant from GlaxoSmithKline.
Submit a Question on Effects of Statins on Triglycerides
Table. Effect of Statins vs Placebo on Triglyceride Levels in 10 Primary and Secondary Placebo-Controlled Outcome Trials
Trial Statin dose (mg) Baseline TG* TG-Lowering Effect Ref
4s Simvastatin 10-40 132 (mean) 10%† [2]
WOSCOPS Pravastatin 40 162 (mean) 12%†‡ [3]
CARE Pravastatin 40 156 (mean) 14%‡ [4]
LIPID Pravastatin 40 142 (median) 11%‡ [5]
PROSPER Pravastatin 40 133 (mean) 13%‡ [6]
AFCAPS Lovastatin 20-40 158§ (median) 13%‡ [7]
ASCOT Atorvastatin 10 150 (mean) 14%‡ [8]
CARDS Atorvastatin 10 173 (mean) 19%‡ [9]
HPS Simvastatin 40 186§ (mean) 14%║ [10]
JUPITER Rosuvastatin 20 118 (median) 17%‡ [11]
AFCAPS = Air Force/Texas Coronary Atherosclerosis Prevention Study; ASCOT = Anglo Scandinavian Cardiac Outcome Trial; CARDS = Collaborative AtoRvastatin Diabetes Study; CARE = Cholesterol and Recurrent Events Study; HPS = Heart Protection Study; JUPITER = Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; LIPID = Long-Term Intervention with Pravastatin in Ischemic Disease; PROSPER = Prospective Study of Pravastatin in the Elderly at Risk; TG = triglyceride; 4s = Scandinavian Simvastatin Survival Study; WOSCOPS = West of Scotland Coronary Prevention Study
* Baseline represents the mean or median TG level of the treatment group at the start of each study, except where noted.
† Compared with baseline
‡ Compared with placebo
§ For all randomized patients
║ Estimated using value for all randomized patients for baseline.
References
1. Stein EA, Lane M, Laskarzewski P. Comparison of statins in hypertriglyceridemia. Am J Cardiol. 1998;81:66B-69B. Abstract
2. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383-1389. Abstract
3. Shepherd J, Cobbe S, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995;333:1301-1307. Abstract
4. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335:1001-1009. Abstract
5. The Long-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;339:1349-1357. Abstract
6. Shepherd J, Blauw G, Murphy M, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:1623-1630. Abstract
7. Downs J, 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. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;279:1615-1622. Abstract
8. Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361:1149-1158. Abstract
9. Colhoun H, Betteridge D, Durrington P, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364:685-696. Abstract
10. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22. Abstract
11. Ridker PM, Danielson E, Fonseca FA, et al.; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195-2207. Abstract
12. Pedersen TR, Olsson AG, Faergeman O, et al. Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). Circulation. 1998;97:1453-1460. Abstract
13. Miller M, Cannon CP, Murphy SA, Qin J, Ray KK, Braunwald E; PROVE IT-TIMI 22 Investigators. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll Cardiol. 2008;51:724-730. Abstract
Michael Miller, MD, FACC, FAHA, Associate Professor of Medicine, Epidemiology, and Preventive Medicine; Director, Center for Preventive Cardiology, Division of Cardiology, University of Maryland Medical Center, Baltimore, Maryland
Disclosure: Michael Miller, MD, FACC, FAHA, has disclosed that he has received grants for clinical research from Abbott Laboratories, AstraZeneca Pharmaceuticals LP, Merck & Co., Inc./Schering-Plough Corporation, Pfizer Inc., and Roche Laboratories Inc. Dr. Miller has also disclosed that he has served as an advisor or consultant to GlaxoSmithKline and Roche Laboratories.
To Print: Click your browser's PRINT button.
NOTE: To view the article with Web enhancements, go to:
http://www.medscape.com/viewarticle/589010
Ask the Experts about Triglycerides in Cardiovascular Disease
What Are the Effects of Statins on Triglycerides and What Are the Results of Major Outcomes Studies?
Michael Miller, MD, FACC, FAHA
Medscape Family Medicine. 2009; ©2009 Medscape
Posted 03/12/2009
Question
What are the effects of statins on triglycerides and what are the results of major outcomes studies?
Response from Michael Miller, MD, FACC, FAHA
Associate Professor of Medicine, Epidemiology, and Preventive Medicine; Director, Center for Preventive Cardiology, Division of Cardiology, University of Maryland Medical Center, Baltimore, Maryland
Although the most prominent effects attributable to statin therapy are its potent low-density lipoprotein cholesterol (LDL-C) lowering properties, it is also well established that statins significantly reduce non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides (TG), and biomarkers of inflammation, most notably C-reactive protein (CRP). Overall, statins reduce TG levels in the range of 10% to 20% ( Table ), although it has been acknowledged that the higher the baseline TG level, the greater the TG-lowering effect. For example, baseline TG levels exceeding 250 mg/dL have been associated with reductions in the range of 22% to 45%, whereas more modest reductions have been observed with lower baseline levels.[1] This can be best identified in randomized, placebo-controlled trials ( Table ). In these outcome studies, the TG cutpoint for study exclusion has generally been 350 mg/dL to 400 mg/dL because higher levels have been viewed as a basis for pharmacologic (eg, nonstatin) treatment. Therefore, it is not surprising that, with few exceptions, the baseline TG in clinical outcome trials that evaluate statin therapy is customarily in the 100 to 200 mg/dL range, with a corresponding TG-lowering effect between 10% and 20%.[2-11] Although no relationship was observed between major coronary heart disease (CHD) events and on-treatment TG in one clinical trial of patients with CHD and high LDL-C,[12] another trial in patients with acute coronary syndrome demonstrated that lower on-treatment TG correlated with reduced CHD events.[13] Therefore, ongoing and future clinical trials will provide additional insight into the relationship between statin (monotherapy and/or combination) therapy, TG lowering, and CHD risk.
This activity is supported by an independent educational grant from GlaxoSmithKline.
Submit a Question on Effects of Statins on Triglycerides
Table. Effect of Statins vs Placebo on Triglyceride Levels in 10 Primary and Secondary Placebo-Controlled Outcome Trials
Trial Statin dose (mg) Baseline TG* TG-Lowering Effect Ref
4s Simvastatin 10-40 132 (mean) 10%† [2]
WOSCOPS Pravastatin 40 162 (mean) 12%†‡ [3]
CARE Pravastatin 40 156 (mean) 14%‡ [4]
LIPID Pravastatin 40 142 (median) 11%‡ [5]
PROSPER Pravastatin 40 133 (mean) 13%‡ [6]
AFCAPS Lovastatin 20-40 158§ (median) 13%‡ [7]
ASCOT Atorvastatin 10 150 (mean) 14%‡ [8]
CARDS Atorvastatin 10 173 (mean) 19%‡ [9]
HPS Simvastatin 40 186§ (mean) 14%║ [10]
JUPITER Rosuvastatin 20 118 (median) 17%‡ [11]
AFCAPS = Air Force/Texas Coronary Atherosclerosis Prevention Study; ASCOT = Anglo Scandinavian Cardiac Outcome Trial; CARDS = Collaborative AtoRvastatin Diabetes Study; CARE = Cholesterol and Recurrent Events Study; HPS = Heart Protection Study; JUPITER = Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; LIPID = Long-Term Intervention with Pravastatin in Ischemic Disease; PROSPER = Prospective Study of Pravastatin in the Elderly at Risk; TG = triglyceride; 4s = Scandinavian Simvastatin Survival Study; WOSCOPS = West of Scotland Coronary Prevention Study
* Baseline represents the mean or median TG level of the treatment group at the start of each study, except where noted.
† Compared with baseline
‡ Compared with placebo
§ For all randomized patients
║ Estimated using value for all randomized patients for baseline.
References
1. Stein EA, Lane M, Laskarzewski P. Comparison of statins in hypertriglyceridemia. Am J Cardiol. 1998;81:66B-69B. Abstract
2. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383-1389. Abstract
3. Shepherd J, Cobbe S, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995;333:1301-1307. Abstract
4. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335:1001-1009. Abstract
5. The Long-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;339:1349-1357. Abstract
6. Shepherd J, Blauw G, Murphy M, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:1623-1630. Abstract
7. Downs J, 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. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;279:1615-1622. Abstract
8. Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361:1149-1158. Abstract
9. Colhoun H, Betteridge D, Durrington P, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364:685-696. Abstract
10. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22. Abstract
11. Ridker PM, Danielson E, Fonseca FA, et al.; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195-2207. Abstract
12. Pedersen TR, Olsson AG, Faergeman O, et al. Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). Circulation. 1998;97:1453-1460. Abstract
13. Miller M, Cannon CP, Murphy SA, Qin J, Ray KK, Braunwald E; PROVE IT-TIMI 22 Investigators. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll Cardiol. 2008;51:724-730. Abstract
Michael Miller, MD, FACC, FAHA, Associate Professor of Medicine, Epidemiology, and Preventive Medicine; Director, Center for Preventive Cardiology, Division of Cardiology, University of Maryland Medical Center, Baltimore, Maryland
Disclosure: Michael Miller, MD, FACC, FAHA, has disclosed that he has received grants for clinical research from Abbott Laboratories, AstraZeneca Pharmaceuticals LP, Merck & Co., Inc./Schering-Plough Corporation, Pfizer Inc., and Roche Laboratories Inc. Dr. Miller has also disclosed that he has served as an advisor or consultant to GlaxoSmithKline and Roche Laboratories.
# posted by roodbont @ 11:58 AM 
