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Virginia ACP MSFM Session - Lipid Management & CVD Risk Reduction -

Virginia ACP MSFM Session - Lipid Management & CVD Risk Reduction -. Q1. What is the evidence that adding a second pharmacologic agent to statin therapy improves cardiovascular outcomes? 1a. Fibrates for high triglyceride 1b. Niacin for low HDL.

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Virginia ACP MSFM Session - Lipid Management & CVD Risk Reduction -

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  1. Virginia ACP MSFM Session- Lipid Management & CVD Risk Reduction - Q1. What is the evidence that adding asecond pharmacologic agent to statin therapy improves cardiovascular outcomes? 1a. Fibrates for high triglyceride 1b. Niacin for low HDL

  2. Relationship Between LDL-C Levels and CHD Events Data derived from epidemiologic studies and RCTs 3.7 2.9 2.2 1.7 1.3 1.0 0 • • Relative Riskof CHD (log scale) • • “Rule of One” applies when LDL < 100 mg/dl • • 40 70 100 130 160 190 220 LDL-Cholesterol (mg/dl) Circulation 2004;110:227-39

  3. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis Lancet 2010; 375: 1875-84 • 18 RCTs published between 1971-2010 • Data for 45,058 patients, including 4552 major CHD events and 3880 deaths • Clofibrate (7 RCTs), Bezafibrate (4 RCTs), Gemfibrozil (3RCTs), Fenofibrate (3 RCTs) and Etofibrate (1 RCT)

  4. … The ACCORD-LIPID study is the first (and only) large-scale RCT (as of March 2013) to evaluate the impact of a fibrate/statin combination versus statin monotherapy on major cardiovascular outcomes.

  5. N Engl J Med 2010; 362: 1563 - 74

  6. J. Am Coll Cardiol 2013; 61: 440-46 • 11 RCTs published between 1975-2011 • Data for 9959 patients, 1547 CHD deaths and non-fatal MIs • Niacin (IR, ER) 0.25- 7.5 gm/day

  7. Effect of Niacin Therapy on Major CHD Events J Am Coll Cardiol 2013;61:440-446

  8. …The AIM-HIGH study is the first (and only) large-scale RCT (as of March 2013) to evaluate the impact of a niacin/statin combination versus statin monotherapy on major cardiovascular outcomes.

  9. N Engl J Med 2011; 365: 2255 - 67

  10. Why Have Trials Failed When a Second Agent is Added to a Statin? ACCORD-LIPID • End-of-study LDL-C 80 mg/dl for statin/placebo vs 81 mg/dl for statin/fenofibrate AIM-HIGH • End-of-study LDL-C 68 mg/dl for statin/placebo vs 65 mg/dl for statin/niacin ER

  11. European Heart J 2011; 32:1769 -1818

  12. Recommendations for the Pharmacological Treatment of Hypercholesterolemia European Heart Journal (2011) 32, 1769-1818

  13. Virginia ACP MSFM Session- Stroke Prevention in AF/AFL - Q2. Given the emergence of several new oral anticoagulants (NOACs), what is the best method to prevent stroke in patients with non-valvular atrial fibrillation or flutter? 2a. Who should receive OAC therapy? 2b. Which OAC is preferred?

  14. Novel Oral Anticoagulants- FDA approved NOACs - Direct Thrombin Inhibitors - Dibigatran (Pradaxa) October 2010 Factor Xa Inhibitors - Rivaroxaban (Xarelto) November 2011 - Apixaban (Eliquis) December 2012

  15. Stroke Prevention Guidelines- 2012 Updates Triggered by NOACs - • Canadian Cardiovascular Society • American College of Chest Physicians • European Society of Cardiology • American Heart/Stroke Association

  16. 2012 Updated AF Guidelines- What are the common themes? - • Physicians tend to underestimate the benefits of OAC and overestimate risk of bleeding, especially in elderly • Most algorithms place greater weight on the deaths/strokes prevented by OAC and less weight on the major bleeds that are caused • Many patients with a CHADS2 score of 1 (and even some with a score of 0) should be offered OAC therapy

  17. 2012 Updated AF Guidelines- What are the Common Themes? - 4. Use of CHA2DS2-VASc scoring index helps stratify “low” and “intermediate” risk patients (CHADS2 = 0-1) • ASA and ASA/Clopidogrel therapy is inferior to OAC (patients should be informed). • AF Strokes are devastating and the #1 preventable cause of stroke.

  18. Advantages of OAC- Strong Evidence from Warfarin RCTs - • Reduce all-cause mortality (~ 28%) • Reduce risk of stroke (~ 68%) • Reduce non-CNS systemic embolism (20-75%) • Net clinical benefit

  19. Atrial fibrillation, anticoagulation, fall risk, and outcomes in elderly patients Matthew B. Sellers, MD, and L. Kristin Newby, MD, MHS Duke University Health System, Durham, North Carolina American Heart Journal 2011; 161: 241-6 …if the annual stroke rate is ≥ 2%, quality-adjusted life expectancy is greatest for OAC, followed by APT and no therapy, respectively. …analysis show that an elderly patient would have to fall ~ 300 times per year for the risk of bleeding complications from falling to outweigh the benefits for prevention of embolic stroke.

  20. Annual Risk of Stroke & OAC Threshold - Original validation cohort study, comprising 1733 pts - Gage, BF, et. al., JAMA 2001; 285: 2864-2870

  21. Safety and Efficacy of OAC versus DAPT - Outcome analysis by CHADS2 score - Healey, JS. Stroke 2008; 39: 1482-86

  22. Recommendations for Antithrombotic Use - Summary of 2012 ESC, ACCP and CCS AF Guidelines - 1 European Heart Journal, 2010; 31: 2369-2429 2 Chest, 2012; 141(2); e531-575 3 Canadian Journal of Cardiology, 2012; 28(2): 125-136

  23. CHA2DS2-VASc and CHADS2 Scores *CAD/prior MI, PAD or aortic plaque

  24. The value of the CHA2DS2-VASc Score for refining stroke risk stratification in patients with atrial fibrillation with a CHADS2 score 0-1: A nationwide cohort study Olesen JB, Torp-Pedersen C, Hansen ML and Lip GY Department of Cardiology, Copenhagen University Hospital and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK Thrombosis and Haemostasis 2012; 107: 1172-79

  25. Olesen, JB. Thrombosis and Haemostasis 2012; 107: 1172-79

  26. Olesen, JB. Thrombosis and Haemostasis 2012; 107: 1172-79

  27. Antithrombotic Management of AF/AFL in CAD * within past year Canadian Journal of Cardiology, 2012; 28(2): 125-136

  28. Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a ‘real world’ atrial fibrillation population: A modelling analysis based on a nationwide cohort study Amitava Banerjee, Dierdre A. Lane, Christian Torp-Pedersen, Gregory Y.H. Lip University of Birmingham Centre for Cardiovascular Sciences, Birmingham, UK; Department of Cardiolgy, Copenhagen University Hospital Gentofte, Denmark Thrombosis and Haemostasis 2012; 107: 584-89

  29. Beneficial Effects of NOACs Compared to Warfarin - The “Big 3” RCT’s, comprising 50,576 AF Patients -

  30. Questions?

  31. 2011; Volume 123: 2292-2333 Triglycerides and Cardiovascular Disease: A Scientific Statement from the American Heart Association Michael Miller, Neil J. Stone, Christie Ballantyne, Vera Bittner, Michael H. Criqui, Henry N. Ginsberg, Anne Carol Goldberg, William James Howard, Marc S. Jacobson, Penny M. Kris-Eterton, Terry A Lennie, Moshe Levi, Theodore Mazzone, Subramian Pennathur

  32. Results of the ACCORD-LIPID Trial % Pts w/Events Years

  33. Results of the AIM-HIGH Trial N Engl J Med 2011; 365:2255-67.

  34. EXPEDITED REVIEW Optimal LDL-C Is 50 to 70 mg/dl Lower Is Better and Physiologically Normal James H. O’Keefe, Jr., Loren Cordain, William H. Harris, Richard M. Moe, and Robert Vogel J Am Coll Cardiol 2004;43:2142-6

  35. Results of the AVERROES Trial - 5559 pts with AF and CHADS2 Score ≥ 1.0, unsuitable for warfarin therapy - Stroke or Systemic Embolism Major Bleeding RRR= 55% Months Months Connolly, SJ, et. al., New England Journal of Medicine 2011; 364: 806–817

  36. AF and Cardio-embolic Stroke- AF is #1 preventable cause of stroke - • Large clot burden – devastating sequalae • Higher mortality (10-25% case fatality) • Greater disability (40% bedriden) • Less responsive to IV thrombolysis • Higher recurrence rate • ICH reduced by 40-75% with NOCAs

  37. Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a ‘real world’ nationwide cohort study Jonas Bjerring Olesen, Gregory Y.H. Lip, jesper Lindhardsen, Deirdre A. Lane, Ole Ahlehoff, Morten Lock Hansen, Jakob Raunso, Janne Schurmann Tolstrup, Peter Riis Hansen, Gunnar Hilmar Gislason, Christian Torp-Pedersen University of Birmingham Centre for Cardiovascular Sciences, and National Institute of Public Health, Copenhagen, Denmark Thrombosis and Haemostasis 2011; 106: 739-49

  38. HAS-BLED Bleeding Risk Score Low Risk = 0-1 Moderate Risk = 2 High Risk ≥ 3

  39. Management of Bleeding in Patients Taking NOAL PCC = prothrombin complex concentrate rF7a = activated recombinant factor VII * With dabigatran

  40. Results of the ARISTOTLE Trial - 18,201 patients with AF and CHADS2 score ≥ 1.0 - Stroke or Systemic Embolism Major Bleeding RRR=21%, p<.01 RRR=31%, p<.001 Months Months Granger, CB, et. al., New England Journal of Medicine 2011; 365: 981-992

  41. ARISTOLE: Intracranial Bleeding

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