1. Update: Lipid Guidelines DO NOT BURN THE COOKIES Amy R. Woods, M.D.

4. a common goal

5. “These guidelines are meant to define practices that meet the needs of patients in most circumstances and are not a replacement for clinical judgment. The ultimate decision about care of a particular patient must be made by the healthcare provider and patient in light of the circumstances presented by that patient. As a result, situations might arise in which deviations from these guidelines may be appropriate. These considerations notwithstanding, in caring for most patients, clinicians can employ the recommendations confidently to reduce the risks of atherosclerotic cardiovascular disease (ASCVD) events.”

6. a little background JUNE 2013 NHLBI ACC AHA 2011 IOM Report 2008 NHLBI 2002 ATP III 2004

7. 4 guidelines published Assessment of CV risk Lifestyle Modifications to reduce CV risk Management of Blood Cholesterol in Adults Management of Overweight and Obesity

8. who are these people? ATP IV = appointed by NHLBI – 13 members plus 3 ex-officio members – PCPs, cardiologists, endocrinologists, experts in lipidology, clinical trials, CV epidemiology and nutrition, and guideline development Reviewed best available RCT, meta-analyses, and observational studies Work Group determined CRITICAL QUESTIONS Formal peer review process Endorsed by many groups (but not endo)

9. ATP III vs ATP IV: differences to consider Limited in scope & not intended to be a comprehensive approach to lipid management Focus on selected CQs Recommendations were mapped using the NHLBI grading format and the ACC/AHA level of evidence construct (alignment is imperfect)

10. Applying Classification of Recommendation and Level of Evidence. Stone N J et al. Circulation. 2014;129:S1-S45 Copyright © American Heart Association, Inc. All rights reserved.

11. public service announcement RECOMMENDATIONS WERE NOT MADE WHEN SUFFICIENT EVIDENCE WAS NOT AVAILABLE

12. our happy place RISK FACTORS & GOALS CHD or RE LDL goal < 100 ≥ 2 RF LDL goal < 130 0 - 1 RF LDL goal < 160 Age Early Fhx CVD HTN Low HDL (<40) tobacco

13. ATP IV: a little more abstract ATP III RISK FACTOR COUNTING TREAT TO LDL GOAL ADDRESS NON-HDL TARGET ATP IV THERE IS NO TARGET THE INTENSITY OF STATIN THERAPY IS THE FOCUS OF TREATMENT

14. so what do the guidelines say? Identify 4 major statin benefit groups for whom ASCVD risk reduction clearly outweighs the risk of adverse events based on a strong body of evidence

15. the 4 statin benefit groups 1) Secondary Prevention in those with clinical ASCVD 2) Primary Prevention in those with LDL ≥ 190 3) Primary Prevention in those with DM, age 40- 75, with LDL 70-189 4) Primary Prevention in those without DM, age 40-75, with LDL 70-189, & a 10 year ASCVD risk ≥ 7.5% (using a new Risk Calculator)

16. 3 critical questions Critical Question 1: – What is the evidence for LDL and non-HDL goals for secondary prevention of ASCVD? Critical Question 2: – What is the evidence for LDL and non-HDL goals for primary prevention of ASCVD? Critical Question 3: – For primary and secondary prevention of ASCVD, what is the impact on lipid levels, effectiveness, and safety of specific cholesterol modifying drugs?

17. clinical vignette # 1 A 63 yo WM smoker with HTN comes to see you for a post hospital f/u visit 1 week after suffering a STEMI. He was discharged on atorvastatin 80 mg, antiplatelet, BB, and ACEI. He recalls that his last PCP had prescribed simvastatin 80 mg years ago and he stopped it secondary to leg cramps. He recalls he was on amlodipine for his HTN at that time as well. He is worried he will have leg cramps and wants to stop the atorvastatin or at least decrease the dosage. What do you tell him?

18. clinical vignette # 1 A: Let him decrease to atorvastatin 20 mg since patients seem to better tolerate this dosage B: Tell him to have a consultation with his chiropractor and get his advice on lipid management C: Check his CK, lipid profile, and liver enzymes now (& at every subsequent visit), then decide D: Explain to him the proven benefit of aggressive secondary prevention with high dose statin therapy

19. CQ 1: Is there evidence to treat to specific LDL or non-HDL targets in secondary prevention? There was NO DATA identified to treat to a specific LDL goal in those with clinical ASCVD 19 RCTs used FIXED DOSE statin therapy In patients with clinical ASCVD, even if moderate or low intensity statin therapy results in an LDL < 100, the evidence suggests that higher intensity statin therapy provides a greater risk reduction in ASCVD events There was NO DATA to support treating to specific non-HDL targets either

21. moderate vs high MODERATE INTENSITY STATIN THERAPY MODERATE intensity lowers LDL by 30-49% Atorvastatin 10 or 20 mg Rosuvastatin 5 or 10 mg Simvastatin 20 or 40 mg Pravastatin 40 or 80 mg Lovastatin 40 mg Fluvastatin 40 mg BID HIGH INTENSITY STATIN THERAPY HIGH intensity lowers LDL by ≥ 50% Atorvastatin 40* or 80 mg Rosuvastatin 20 or 40 mg *IDEAL down-titrated to 40 mg when 80 was not tolerated

22. even though we don’t treat to target… Most RCTs showed that HIGH intensity statin therapy brings most individuals to an LDL < 100

23. tidbits In those patients > 75 years old, MODERATE intensity statin therapy showed a better RR in secondary prevention The evidence supports continuation of statins in those > 75 in persons already on them and tolerating them well Routine CK and ALT monitoring not necessary

24. the dreaded PA

25. clinical vignette # 2 A 60 BF presents to you for follow up. At her last visit you mentioned that you wanted to talk to her about statin therapy to decrease her risk of stroke & MI. She is very concerned because she has been seeing the ads on TV asking patients to call 1800-SUE-DOCS if you developed diabetes while taking statin therapy. The patient does not smoke, she is treated with 2 anti- hypertensives (treated BP 142/88), her BMI is 31. Her mother was diabetic and had CVA at age 62. The patient’s lipid profile shows TC 200, LDL 125, HDL 55, TG 130. Fasting glucose is 109, A1c is 5.9%. Using the risk calculator, her 10 year estimated risk of ASCVD is 8.7%. So what do you advise?

26. clinical vignette # 2 A: She should focus only on LSM because LSM reduce ASCVD more than any statin could dream of, and you don’t want to get sued B: Go ahead and put her on Bydureon to help cancel out the risk of diabetes development then add pravastatin 10 mg daily C: Measure carotid intima media thickness & obtain a BOSTON advanced lipid profile, then decide D: Have a RISK DISCUSSION and recommend that she start a moderate or high intensity statin

27. Stone N J et al. Circulation. 2014;129:S1-S45 Copyright © American Heart Association, Inc. All rights reserved.

28. CQ 2: Is there evidence to treat to specific LDL and non- HDL targets in primary prevention? There was NO DATA to treat to specific LDL targets There was NO DATA to treat to specific non- HDL targets – RCTs used FIXED DOSE statin therapy AFCAPS/TEXCAPS MEGA JUPITER

29. the risk calculator

30. Use it to calculate a 10 year risk of first ASCVD event in those without ASCVD, ages 40-75, with an LDL 70-189. Can be used in those WITH DM or those WITHOUT DM If the 10 year risk is > 7.5%, the benefit of statin therapy clearly outweighs the risk Those with a 10 year risk of 5 – 7.5% showed a similar RR however the potential for AE > RR

31. the risk calculator Based on pooled cohort equations for RCTs – ARIC, CHS, CARDIA, Framingham & Offspring Cohorts Variables that met inclusion criteria: – Age, TC, HDL, systolic BP, DM smoking status Applicable to non-Hispanic whites and AA Admittedly OVER-estimates for Hispanic & Asian American populations Admittedly UNDER-estimates for American Indian populations

32. the risk calculator Recommendation for use of the risk calculator in AA and whites: – NHLBI: Grade = B recommendation (moderate) – ACC/AHA COR: Class = I (benefit > risk) – Level of Evidence = B (limited populations) Recommendation for use of the risk calculator in other populations: – NHLBI: Grade = E recommendation – ACC/AHA COR: Class = IIb (benefit ≥ risk) – Level of Evidence = C (expert opinion)

33. the risk discussion Shared decision making A time to revisit LSM and address other RF Discuss potential for ASCVD risk reduction Discuss adverse effects – New onset DM (dose dependent) 1 per 1000 in moderate intensity (prevention of 5.4 ASCVD events) 3 per 1000 in high intensity (5.9 ASCVD events) – Myopathy & Hemorrhagic CVA Discuss drug – drug interactions Discuss patient preferences ATP III goal LDL < 130 due to age, HTN, neutral HDL

34. if you like ordering more tests.. In primary prevention, if the risk-based decision is unclear, consider: – Family hx of premature CVD – Hs CRP – CAC – ABIs

35. doc, can you explain this to me?

36. clinical vignette # 3 A 58 yo WM with hx of 3 v CABG about 2 years ago comes in to see you for follow up. He is not smoking. He is taking his meds as prescribed. He exercises regularly. BP is well controlled and BMI is 24. On rosuvastatin 40 mg his LDL is 116, HDL is 32, TG 145. Should you add more medications to his regimen of asa, BB, statin, long acting nitrate, and diuretic/ACE in order to get his lipid profile in better standing?

37. clinical vignette # 3 A: Add VASCEPA – EPA all the way baby B: Add ezetimibe because he remembers being on it once but stopped it due to $$$ C: Add NIACIN to get his HDL out of the red zone and back into the black zone D: Let him ride

38. CQ 3: For primary and secondary prevention, what is the impact on lipids levels, effectiveness, and safety of specific cholesterol modifying drugs? NO DATA to support routine use of non-statin drugs combined with statin therapy to further reduce ASCVD events – Review included statins, fibrates, niacin, bile acid sequestrants, ezetimibe, O-3 fatty acids – AIM-HIGH: adding NIACIN to achieve non-HDL targets did NOT reduce ASCVD risk NO DATA for ASCVD outcomes in statin intolerant patients

39. a public service announcement worth repeating RECOMMENDATIONS WERE NOT MADE WHEN SUFFICIENT EVIDENCE WAS NOT AVAILABLE

40. but When treating high risk patients who have a less than anticipated response to statins, or who are unable to tolerate less than recommended intensity of statin therapy, or who are completely statin intolerant, one may consider a non-statin cholesterol lowering therapy

41. new drugs & other targets inhibition of CETP=increases HDL ILLUMINATE OUTCOMES

42. new drugs & other targets GAUSS-2 LAPLACE-2 DESCARTES FOURIER

43. Summary of Statin Initiation Recommendations for the Treatment of Blood Cholesterol to Reduce ASCVD Risk in Adults (See Figures 3, 4, and 5 for More Detailed Management Information). Stone N J et al. Circulation. 2014;129:S1-S45 Copyright © American Heart Association, Inc. All rights reserved.

44. ATP IV strengths to consider Encourages a “risk discussion” with patients in regards to primary prevention Strictly evidence based The bulk of the content is undisputed 10 year risk of ASCVD includes CHD & stroke More relevant for women and AA populations

45. ATP IV weaknesses to consider Strictly evidence based – Limited or NO DATA for > 75 and < 40 The risk calculator is controversial* and may significantly overestimate risk Forgotten populations: diabetics < 40 y/o and other high risk groups Younger patients often have a high lifetime risk and a low short term (10 year) risk

46. afterthoughts RCT consider defined populations Risk estimation is based on group averages which are then applied to individual patients in practice Guidelines are made to inform us, rather to replace clinical judgment Anticipate an update forthcoming….

47. afterthoughts Individual with the SAME estimated risk WILL either have, or not have, the event of interest and only those patients who are destined to have an event can have their risk prevented by therapy

49. so what do we do now? DO NOT BURN THE COOKIES

50. references http://www.nhlbi.nih.gov/guidelines/cvd_adult/risk_assessment http://my.americanheart.org/cvriskcalculator http://www.medscape.com Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB Sr, Gibbons R, Greenland P, Lackland DT, Levy D, O’Donnell CJ, Robinson JG, Schwartz JS, Shero ST, Smith SC Jr, Sorlie P, Stone NJ, Wilson PWF. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(suppl 2):S49-S73. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PWF. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(suppl 2):S1–S45.