• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content
PPT
 

PPT

on

  • 2,186 views

 

Statistics

Views

Total Views
2,186
Views on SlideShare
2,186
Embed Views
0

Actions

Likes
1
Downloads
82
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    PPT PPT Presentation Transcript

    • Mixed Dyslipidemia – Attenuating risk- treatment beyond LDL. Michael Davidson, MD Executive Medical Director Radiant Research; Director Preventive Cardiology Center; Professor of Medicine Rush University Medical Center Chicago, IL. Christie Ballantyne, MD Professor of Atherosclerosis and Lipoprotein Research; Director Center for Cardiovascular Disease Prevention Baylor College of Medicine and Methodist DeBakey Heart Center, Houston, TX.
    • Residual Cardiovascular Risk in Major Statin Trials 4 HPS Collaborative Group. Lancet . 2002;360:7-22. 5 Shepherd J, et al. N Engl J Med. 1995;333:1301-1307 6 Downs JR, et al. JAMA. 1998;279:1615-1622. 1 4S Group. Lancet. 1994;344:1383-1389. 2 LIPID Study Group. N Engl J Med. 1998;339:1349-1357. 3 Sacks FM, et al. N Engl J Med. 1996;335:1001-1009.  LDL-C N 4444 4159 20 536 6595 6605 9014 -35% -28% -29% -26% -25% -25% Secondary High Risk Primary Patients Experiencing Major CHD Events, % 4S 1 LIPID 2 CARE 3 HPS 4 WOSCOPS 5 AFCAPS/ TexCAPS 6 19.4 12.3 10.2 8.7 5.5 6.8 28.0 15.9 13.2 11.8 7.9 10.9 CHD events occur in patients treated with statins
    • HDL-C* (mg/dL) Major CVD Events, % Patients With LDL-C ≤ 80 mg/dL on Atorvastatin 80 mg n = 4874 *On-treatment level (3 months) Barter P, et al. Poster ACC. 2006. Abstract 914-203. ≤ 40 41-50 51-60 >60 P < 0.0001 for Inverse Relationship Treating to New Targets (TNT) Study Low HDL-C Increases CVD Risk Even if LDL-C Levels Are Well-Controlled
      • Pathophysiology
      • Patients with high triglycerides:
      • Increase in VLDL remnants
      • Increase in IDL
      • Small, dense LDL
      • Lp-PLA2 and Apo-CIII - pro-atherogenic
      • Even on statins – these patients have increased risk
      • What is optimum TG level?
      • Guidelines : < 150
      • In patients with coronary disease, worsening disease, recurrent symptoms, <100 may be optimal.
      • TG/HDL Ratio = 3.5
      Lp-PLA2: lipoprotein-associated phospholipase A2 APO-CIII: Apolipoprotein CIII
      • Beyond LDL as a Target
      • Addressed in guidelines as concept of &quot;non-HDL-cholesterol&quot;
      • Not a new concept: Helsinki Heart Study of 1987 entry criteria was high levels of non-HDL-C 1
      • Target non-HDL < 100 (but not routinely on lab request slip)
      • ADA Expert Panel: Patients with type 2 diabetes and other risk factors should also have non-HDL < 100; apoB goal < 90 mg/dl, LDL particle number < 1000 2
      1. Frick et al. N Engl J Med. 1987;317:1237-1245. 2. Brunzell et al. Diabetes Care 31: 811-822
    • Non–HDL-C Superior to LDL-C in Predicting CHD Risk Liu J, et al . Am J Cardiol. 2006;98:1363-1368. Non–HDL-C, mg/dL Relative CHD Risk LDL-C, mg/dL
      • Within non-HDL-C levels, no association was found between LDL-C and the risk for CHD.
      • In contrast, a strong positive and graded association between non–HDL-C and risk for CHD occurred within every level of LDL-C
      • Non–HDL-C is a stronger predictor of CHD risk than LDL-C
    • Residual CVD Risk in Patients Treated With Intensive Statin Therapy Standard statin therapy Intensive high-dose statin therapy PROVE IT-TIMI 22 1 IDEAL 2 TNT 3 N LDL-C,* mg/dL 1 Cannon CP, et al. N Engl J Med. 2004;350:1495-1504. 2 Pedersen TR, et al. JAMA. 2005;294:2437-2445. 3 LaRosa JC, et al. N Engl J Med. 2005;352:1425-1435. 4162 8888 10 001 95 *Mean or median LDL-C after treatment 62 104 81 101 77 26.3 13.7 10.9 12.0 22.4 8.7 Patients Experiencing Major CVD Events, %
    • Statin/ Fibrate Combination Therapy: Pharmacokinetic Interactions Backman JT, et al. Clin Pharmacol Ther . 2002;72:685-691. Abbott Laboratories. Data on file; 2005. Davidson MH. Am J Cardiol. 2002;90(suppl):50K-60K. Prueksaritanont T, et al. Drug Metab Dispos. 2002;30:1280-1287. Martin PD, et al. Clin Ther . 2003;25:459-471. Bergman AJ, et al. J Clin Pharmacol . 2004;44:1054-1062. Backman JT, et al. Clin Pharmacol Ther. 2005;78:154-67. TriCor [PI]. Abbott Laboratories;2004. Kyrklund C, et al. Clin Pharmacol Ther . 2001;69:340-345. Pan W-J, et al. J Clin Pharmacol . 2000;40:316-323. Backman JT, et al. Clin Pharmacol Ther . 2000;68:122-129 . Gemfibrozil Fenofibrate Atorvastatin  in C max by 2.7-fold No effect Simvastatin  in C max by 2-fold No effect Pravastatin  in C max by 2-fold No effect Rosuvastatin  in C max by 2-fold No effect Fluvastatin No effect No effect Lovastatin  in C max by 2.8-fold No effect Cerivastatin  in C max by 2-3 – fold No effect
      • New agent : ABT-335 is being studies in combination with simvastatin and with atorvastatin. Study results at ACC 08 - good efficacy and safety in lowering TG and raising HDL
      • Good safety data for extended-release niacin plus statins but some adherence/dose titration issues
      • In patients with high/very high TG, and poorly controlled diabetes, fenofibrate or fenofibrate plus omega-3 fatty acids may be better choice
      • Other benefits of fenofibrate on small vessels disease
      • SEACOAST data: niacin raises HDL independent of TG level
      • Fenofibrate requires TG to be high to raise HDL
      • Generally, men tolerate niacin better than women
      • AIM HIGH: Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes 1
      • ER niacin plus simvastatin vs simvastatin alone at comparable levels of on-treatment LDL-C
      • n = 3,300
      • Completion Q3, 2010
      • HPS2-THRIVE: A Randomized Trial of the Long-Term Clinical Effects of Raising HDL Cholesterol With Extended Release Niacin/Laropiprant 2
      • Participants have established CVD and receive LDL lowering therapy (40 mg of simvastatin or 10/40 mg ezetimibe/simvastatin)
      • Laropiprant - selective prostaglandin D2 receptor-1 (DP1) antagonist -reduces frequency and intensity of niacin-induced flushing
      • n = 20,000
      • Completion Q4, 2011
      1. http://clinicaltrials.gov/ct/show/NCT00120289 2. http://www.controlled-trials.com/ISRCTN29503772
      • ACCORD: Action to Control Cardiovascular Risk in Diabetes
      • Clinical benefit of adding fenofibrate to patients receiving simvastatin therapy
      • n = 5,900 Completion Q3, 2009
      • FIRST: The effects of Fenofibrate on cIMT in patients with Residual risk on Statin Therapy 1
      • Safety and efficacy study of ABT-335 in combination with atorvastatin
      • Uses carotid intima media thickness as surrogate end point
      • Recruiting
      • ARBITER-2: Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 2
      • ER niacin added to lipid-lowering therapy in patients with known CHD and low HDL-C levels
      • Mean CIMT increased significantly in those not treated with niacin, while no significant increase in CIMT was found in the niacin-treated patients.
      1. http://clinicaltrials.gov/ct2/show/NCT00616772 2. Taylor et al. Circulation 110 (2004), pp. 3512–3517
    • Summary
      • Residual risk remains when LDL is low, but TG remains high, HDL is low
      • Diet and exercise are foundation to therapy
      • Aspirin therapy, blood pressure and diabetes control
      • Need to correct metabolic &quot;derangement&quot; to improve patient outcomes - less progression of disease, fewer CV events
      • Combination therapy control all abnormal lipids to achieve LDL < 70 ; TG < 150 and HDL > 40 - don’t see events