Hyperlipidemia. Intern Immersion Block 2015

Transcription

1 Hyperlipidemia Intern Immersion Block 2015 Christopher Wong, MD Division of General Internal Medicine University of Washington

2 Welcome!

3 Disclosures: royalties from book sales (not relevant to this talk) (all of which I donate)

4 There are new guidelines!!!

5 There are new guidelines!!! Not etched in stone...

6 There are new guidelines!!! Not etched in stone... Just because they are new does not mean they are right

7 There are new guidelines!!! Not etched in stone... Just because they are new does not mean they are right But the the old ones were not necessarily right either

8 There are new guidelines!!! What are we going to talk about: Old guidelines New guidelines Common questions

9 The old way

10 Case: the old way A 60 year old man with hypertension and diabetes has an LDL of 180, HDL 35 and total cholesterol 245. What is this patient s LDL goal? A Less than 130 B Less than 100 C Less than 70 D Less than zero

11 ATPIII Age: Male 45 / Female 55 Family History: premature CHD Smoking Hypertension HDL <40 Negative risk factor: HDL 60+ RISK RFs 10 YEAR CATEGORY RISK LDL GOAL LOW 0-1 <10% <160 > 190 MODERATE 2+ <10% <130 >160 Meds upfront MODERAT ELY HIGH RISK % <130 >130 HIGH CHD or Equivalent >20% <100 Op#onal <70 >130

12 Case: the old way A 60 year old man with hypertension and diabetes has an LDL of 180, HDL 35 and total cholesterol 245. What is this patient s LDL goal? A Less than 130 B Less than 100 C Less than 70 D Less than zero

13 Case: the old way A 60 year old man with hypertension and diabetes has an LDL of 180, HDL 35 and total cholesterol 245. What is this patient s LDL goal? A Less than 130 B Less than 100 C Less than 70 D Less than zero

14 ATP III: Treatment Meds: Statins Bile acid sequestrants (!) TLC Diet Reduce saturated fat and cholesterol intake More fiber and sterols/stanols Exercise Lose weight

15 2002 Adult Treatment Panel III (ATP-III) 2004 Update NCEP National Cholesterol Educational Program

16 2002 Adult Treatment Panel III (ATP-III) 2004 Update NCEP National Cholesterol Educational Program 2004 George W Abu Ghraib Tony Blair Libya Red Sox 2013 finally... Before the era of: You Tube Katrina iphone Tsunami Barack Obama Economic crisis Affordable Care Act College (for some of you)

17 It wasn t a problem just because it was old

18 2 patients with diabetes 60 year old woman Diabetes LDL 110 LDL year old woman Diabetes LDL 160 LDL 90

19 2 patients with diabetes 60 year old woman Diabetes LDL 110 LDL year old woman Diabetes LDL 160 LDL 90 Both are treated to LDL goals. Which patient achieved greater risk reduction?

20 2 patients with diabetes 60 year old woman Diabetes LDL 110 LDL year old woman Diabetes LDL 160 LDL 105

21 2 patients with diabetes 60 year old woman Diabetes LDL 110 LDL year old woman Diabetes LDL 160 LDL 105 Only one patient achieved LDL goal < 100. Which achieved greater risk reduction?

22 Problems Treating to LDL goals: How were studies of cholesterol lowering done?

23 Almost all trials with clinical endpoints Fixed dose of stasn versus Placebo or One stasn versus Another stasn

24 The mechanics of cholesterol lowering: what do (did) we actually do? Screen lipids à if high, start lifestyle changes Recheck lipids à if still high, start medication Recheck lipids à if still high, increase medication Recheck lipids à if stable, recheck next year Patient has new RF à change LDL goal, change or increase meds à recheck lipids

25 Problems with LDL strategy No studies have ever been done screening and treating to LDL targets Statins, which have the strongest evidence, reduce risk over wide range of lipid levels Hayward & Krumholz. Circ Cardiovasc Qual Outcomes 2012; 5:2-5

26 55M Nonsmoker SBP 120 HDL 55 CRP 5 (-) family history LDL M Smoker SBP 140 HDL 25 CRP 5 (+) family history LDL 90 5 yr risk ~ 3% NNT = 83 5 yr risk ~ 8% NNT = 31 Hayward & Krumholz. Circ Cardiovasc Qual Outcomes 2012; 5:2-5

27 New guidelines

28 Remember this: How much risk? How much treatment?

29 Remember this: How much risk? How much treatment?

30 Remember this: How much risk? How much treatment?

31 Remember this: How much risk? How much treatment?

32 Remember this: How much risk? How much treatment?

33 Remember this: How much risk? How 84 pages! much treatment?

34 New guidelines case 1 60 year old man, MI last year, on aspirin, clopidogrel, lisinopril, metoprolol. Forgot to refill statin. Primary or Secondary prevention?

35 New guidelines case 1 60 year old man, MI last year, on aspirin, clopidogrel, lisinopril, metoprolol. Forgot to refill statin. Primary or Secondary prevention?

36 New guidelines case 1 60 year old man, MI last year, on aspirin, clopidogrel, lisinopril, metoprolol. Forgot to refill statin. Primary or Secondary prevention? Risk? High Moderate Low

37 New guidelines case 1 60 year old man, MI last year, on aspirin, clopidogrel, lisinopril, metoprolol. Forgot to refill statin. Primary or Secondary prevention? Old guidelines? Risk? High Moderate Low

38 New guidelines case 1 60 year old man, MI last year, on aspirin, clopidogrel, lisinopril, metoprolol. Forgot to refill statin. Primary or Secondary prevention? Risk? High Moderate Low Old guidelines? Titrate to LDL

39 New guidelines case 1 60 year old man, MI last year, on aspirin, clopidogrel, lisinopril, metoprolol. Forgot to refill statin. Treatment: Statin Risk category: clinical atherosclerotic disease New guidelines Age 75: high intensity (or moderate if cannot tolerate) Age > 75: moderate intensity

40 Risk category: clinical atherosclerotic disease Cerebrovascular: stroke, TIA PAD: peripheral arterial disease CAD: -acute coronary syndromes -history of MI -stable or unstable angina Revascularization: coronary or other arterial revascularization

41 What is high intensity?

42 What is high intensity? Drug High Intensity (mg) Moderate Intensity (mg) AtorvastaSn 80 (40?) 10 (20?) Low Intensity (mg) RosuvastaSn SimvastaSn (?) PravastaSn LovastaSn 40 20

43 What is high intensity? Drug High Intensity (mg) Moderate Intensity (mg) AtorvastaSn 80 (40?) 10 (20?) Low Intensity (mg) RosuvastaSn SimvastaSn (?) PravastaSn LovastaSn 40 20

44

45 New guidelines case 2 60 year old woman with diabetes, no heart attack etc. Primary or Secondary prevention? Risk: High Moderate Low

46 New guidelines case 2 60 year old woman with diabetes, no heart attack etc. Primary or Secondary prevention? Old guidelines? Risk: High Moderate Low

47 New guidelines case 2 60 year old woman with diabetes, no heart attack etc. Primary or Secondary prevention? Old guidelines? Risk: High Moderate Low Same as case #1 ischemic equivalent

48 New guidelines case 2 60 year old woman with diabetes, no heart attack etc. Risk category: Diabetes Type 1 or 2 Age Treatment: Moderate intensity statin. New guidelines If risk 7.5%, then high-intensity statin

49 New guidelines case 2 60 year old woman with diabetes, no heart attack etc. Risk category: Diabetes Type 1 or 2 Age New guidelines Treatment: Moderate intensity statin. atorvastatin simvastatin If risk 7.5%, then high-intensity statin atorvastatin rosuvastatin 20

50 How to estimate risk?

51 How to estimate risk? Framingham, MA The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again.

52 Framingham

53 Framingham MI / death Simple Easy to use Easily found data

54 Framingham MI / death Simple Not for those Easy to use with CAD or Easily found data DM!

55 How to estimate risk?

56 How to estimate risk? New guidelines: they made their own risk calculator

57 How to estimate risk? New guidelines: they made their own risk calculator Data from Cholesterol Trialists Collaboration

58 How to estimate risk? New guidelines: they made their own risk calculator Data from Cholesterol MI and stroke Trialists Collaboration

59 New guidelines case 2 60 year old woman with diabetes, no heart attack etc. Non-smoker, TC 220 HDL 35, on BP meds, SBP 120. New guidelines: Treatment: Risk category: Diabetes Type 1 or 2 Age Moderate intensity statin. atorvastatin simvastatin If risk 7.5%, then high-intensity statin

60 New guidelines case 2 60 year old woman with diabetes, no heart attack etc. Non-smoker, TC 220 HDL 35, on BP meds, SBP 120. New guidelines: Risk category: Diabetes Type 1 or 2 Age Treatment: Moderate intensity statin. atorvastatin simvastatin If risk 7.5%, then high-intensity statin

61

62 New guidelines case 3 55 year old, regular guy. No CV disease or DM. No meds. TC 250 HDL 45 LDL 170. SBP 130. Nonsmoker.

63 New guidelines case 3 55 year old, regular guy. No CV disease or DM. No meds. TC 250 HDL 45 LDL 170. SBP 130. Nonsmoker. Primary or Secondary prevention? Risk: High Medium Low

64 New guidelines case 3 55 year old, regular guy. No CV disease or DM. No meds. TC 250 HDL 45 LDL 170. SBP 130. Nonsmoker. Primary or Secondary prevention? Risk: High Medium Low Old guidelines? 0-1 risk factor male > 45 LDL goal < 160 Meds at > 190 or fail lifestyle changes

65 New guidelines case 3 55 year old, regular guy. No CV disease or DM. No meds. TC 250 HDL 45 LDL 170. SBP 130. Nonsmoker. New guidelines

66 New guidelines case 3 55 year old, regular guy. No CV disease or DM. No meds. TC 250 HDL 45 LDL 170. SBP 130. Nonsmoker. 10 yr risk 7.5%: Moderate to high intensity statin New guidelines

67

68 New guidelines case 4 One more category to know: LDL 190 Considered high risk Consider evaluation for familial syndrome

69 New guidelines case 4 One more category to know: LDL 190 Considered high risk Consider evaluation for familial syndrome Treatment: High intensity statin Moderate if unable to tolerate

70 Risk category Secondary preven#on Clinical No AtheroscleroTc Cardiovascular Disease Calculate risk? Treatment High intensity stasn Moderate if Age > 75 or cannot tolerate high intensity dosing Primary preven#on LDL 190 No High intensity stasn Moderate if cannot tolerate Notes Diabetes Yes 10 year risk < 7.5%: moderate intensity 7.5%: high intensity LDL < 190 no DM Yes 10 year risk 7.5%: moderate to high intensity < 7.5%: individualize

71 But wait not everyone is happy with the new guidelines

72 Risk category Secondary preven#on Clinical No AtheroscleroTc Cardiovascular Disease Calculate risk? Treatment High intensity stasn Moderate if Age > 75 or cannot tolerate high intensity dosing Primary preven#on LDL 190 No High intensity stasn Moderate if cannot tolerate Diabetes Yes 10 year risk < 7.5%: moderate intensity 7.5%: high intensity LDL < 190 no DM Yes 10 year risk 7.5%: moderate to high intensity < 7.5%: individualize #1: not all evidence levels are the same Notes How long to do high intensity? Not much evidence for > 75 years old Slightly weaker level of evidence. High intensity b/c how far to go. Moderate intensity: strong level of evidence Higher intensity: weaker evidence (IIa / B) They consider this a I/ A rec.

73 Risk category Secondary preven#on Clinical No AtheroscleroTc Cardiovascular Disease Calculate risk? Treatment High intensity stasn Moderate if Age > 75 or cannot tolerate high intensity dosing Primary preven#on LDL 190 No High intensity stasn Moderate if cannot tolerate Diabetes Yes 10 year risk < 7.5%: moderate intensity 7.5%: high intensity LDL < 190 no DM Yes 10 year risk 7.5%: moderate to high intensity < 7.5%: individualize #1: not all evidence levels are the same Notes How long to do high intensity? Not much evidence for > 75 years old Slightly weaker level of evidence. High intensity b/c how far to go. Moderate intensity: strong level of evidence Higher intensity: weaker evidence (IIa / B) They consider this a I/ A rec.

74 Risk category Secondary preven#on Clinical No AtheroscleroTc Cardiovascular Disease Calculate risk? Treatment High intensity stasn Moderate if Age > 75 or cannot tolerate high intensity dosing Primary preven#on LDL 190 No High intensity stasn Moderate if cannot tolerate Diabetes Yes 10 year risk < 7.5%: moderate intensity 7.5%: high intensity LDL < 190 no DM Yes 10 year risk 7.5%: moderate to high intensity < 7.5%: individualize #1: not all evidence levels are the same Notes How long to do high intensity? Not much evidence for > 75 years old Slightly weaker level of evidence. High intensity b/c how far to go. Moderate intensity: strong level of evidence Higher intensity: weaker evidence (IIa / B) They consider this a I/ A rec.

75 Risk category Secondary preven#on Clinical No AtheroscleroTc Cardiovascular Disease Calculate risk? Treatment High intensity stasn Moderate if Age > 75 or cannot tolerate high intensity dosing Primary preven#on LDL 190 No High intensity stasn Moderate if cannot tolerate Diabetes Yes 10 year risk < 7.5%: moderate intensity 7.5%: high intensity LDL < 190 no DM Yes 10 year risk 7.5%: moderate to high intensity < 7.5%: individualize #1: not all evidence levels are the same Notes How long to do high intensity? Not much evidence for > 75 years old Slightly weaker level of evidence. High intensity b/c how far to go. Moderate intensity: strong level of evidence Higher intensity: weaker evidence (IIa / B) They consider this a I/ A rec.

76 New guidelines: controversies #2: the risk calculator: at extremes performs weirdly #3: threshold for primary prevention 7.5%? Too low or too high? (Is there any number everyone would agree on?) this is a value/judgment call, not evidence #4: how long to do high intensity therapy? And finally, #5: some people don t think statins work at all for primary prevention

77 New guidelines: controversies #2: the risk calculator: at extremes performs weirdly #3: threshold for primary prevention 7.5%? Too low or too high? (Is there any number everyone would agree on?) this is a value/judgment call, not evidence #4: how long to do high intensity therapy? And finally, #5: some people don t think statins work at all for primary prevention

78 New guidelines: controversies #2: the risk calculator: at extremes performs weirdly #3: threshold for primary prevention 7.5%? Too low or too high? (Is there any number everyone would agree on?) this is a value/judgment call, not evidence #4: how long to do high intensity therapy? And finally, #5: some people don t think statins work at all for primary prevention

79 So what (in general) do I actually do?

80 Risk category Secondary preven#on Clinical No AtheroscleroTc Cardiovascular Disease Calculate risk? Treatment High intensity stasn Moderate if Age > 75 or cannot tolerate high intensity dosing Primary preven#on LDL 190 No High intensity stasn Moderate if cannot tolerate Notes Yes, but might step down after a few years More likely to use moderate Diabetes Yes 10 year risk < 7.5%: moderate intensity 7.5%: high intensity More likely to use moderate LDL < 190 no DM Yes 10 year risk 7.5%: moderate to high intensity < 7.5%: individualize More likely to use moderate

81 New guidelines case 1 60 year old man, MI last year, on aspirin, clopidogrel, lisinopril, metoprolol. Forgot to refill statin. High dose statin is reasonable why? Very high risk, just had an MI Risks of statin seem acceptable

82 New guidelines case 2 60 year old woman with diabetes, no heart attack etc. Non-smoker, TC 220 HDL 35, on BP meds, SBP 120. New guidelines: Risk category: Diabetes Type 1 or 2 Age I d probably stick with moderate intensity (Heart Protection Study) atorvastatin simvastatin Increase if patient is wanting to lower risk further, accept some increased statin side effects. atorvastatin rosuvastatin 20

83 New guidelines case 3 55 year old, regular guy. No CV disease or DM. No meds. TC 250 HDL 45 LDL 170. SBP 130. Nonsmoker. 10 yr risk 7.5%: Moderate to high intensity statin I d discuss risks and benefits. If he wants to take a pill to lower his risk, and is ok with possible side effects, then start a statin. Start with moderate dose.

84 What do other organizations advocate? VA guidelines (2014) -secondary prevention: mod-high dose statin -risk > 12%: mod dose statin -risk 6-12%: mod dose statin (shared dec) Risk < 6%: none NICE (2014) -QRISK2 score -Risk >10%: atorvastatin 20 mg -CVD: atorvastatin 80 mg USPSTF???

85 Common questions

86 When do I start screening?

87 When do I start screening? Old guidelines: all adults 20 years or older New guidelines: They don t really say, but the risk calculator starts at age USPSTF: Men 35, or younger if RFs Women if RFs. (reality: most would screen women 45) Younger pasents: if increased risk

88 What do I order? A. Fasting lipid panel B. Non-fasting lipid panel C. Total and HDL, fasting D. Total and HDL, non-fasting

89 Fasting vs non-fasting FasTng Non- fastng Total and HDL Lipid panel FasSng lipid panel preferred. Can screen for DM also Lower triglycerides (usually), more likely to be able to calculate an LDL Less convenient pasents may not return for a fassng test More opportunissc / convenient Does not affect total and HDL anyway May have high triglycerides and end up repeasng it fassng Total and HDL not affected by diet Risk calculator uses total and HDL USPSTF: total and HDL High LDL is a risk category in current guidelines FasSng lipid panel preferred. Cost?

90 Lipid panel vs total/hdl FasTng Non- fastng Total and HDL Lipid panel FasSng lipid panel preferred. Can screen for DM also Lower triglycerides (usually), more likely to be able to calculate an LDL Less convenient pasents may not return for a fassng test More opportunissc / convenient Does not affect total and HDL anyway May have high triglycerides and end up repeasng it fassng Total and HDL not affected by diet Risk calculator uses total and HDL USPSTF: total and HDL High LDL is a risk category in current guidelines FasSng lipid panel preferred. Cost?

91 Lipid panel vs total/hdl FasTng Non- fastng Total and HDL Lipid panel FasSng lipid panel preferred. Can screen for DM also Lower triglycerides (usually), more likely to be able to calculate an LDL Less convenient pasents may not return for a fassng test More opportunissc / convenient Does not affect total and HDL anyway Total and HDL not affected by diet Risk calculator uses total and HDL USPSTF: total and HDL à I generally order a lipid panel (not just total/hdl), May have high High LDL is a risk and triglycerides decide and with category the patient in current end up repeasng it guidelines on fassng fasting vs non-fasting FasSng lipid panel preferred. Cost?

92 What about lp(a) and all those other particles?

93 Panel or total/hdl? HDL total LDL Other stuff } all bad!

94 How often should I recheck the lipid panel?

95 Rechecking lipid panels Not everybody needs a yearly lipid panel! Not on treatment: every 4-6 years (age 40-75, without cardiovascular disease or DM, and with LDL )

96 Rechecking lipid panels On treatment: Recheck 4-12 weeks expect high intensity to reduce 50%+ expect moderate to reduce 30-50% Assess adherence and response

97 Rechecking lipid panels On treatment: Recheck 4-12 weeks expect high intensity to reduce 50%+ expect moderate to reduce 30-50% Assess adherence and response Controversial... Are we titrating to response instead of goal? Is it necessary? Guidelines say you can use your judgment on this one if you don t get expected response

98 What laboratory monitoring is needed on statin therapy? AST, ALT CK Creatinine

99 What laboratory monitoring is needed on statin therapy? AST, ALT baseline, 12 wks, annually CK baseline, then if symptoms

100 What laboratory monitoring is needed on statin therapy? AST, ALT baseline, 12 wks, annually CK baseline, then if symptoms Creatinine

101 My patient c/o muscle aches on a statin. What to do next?

102 Statin-induced myalgias Believe your patient! Can check CK if you suspect myopathy Options D/C and restart at lower dose (current guidelines) D/C and start low dose of a different statin Red yeast rice? Coenzyme Q10? à recent Meta-analysis negative. Consider how much you need the LDLlowering (Risk Assessment, Risk Reduction)

103 Do statins cause diabetes?

104 Do statins cause diabetes? Probably JUPITER trial Meta-analyses Effect might be small Lancet 2010 / JAMA 2011 In 1 year, ~ 1 in 1000 cases High dose NNH 500 compared with moderate dose à dose dependent Screening for DM: no different than in those without statins

105 Statins and DM: new stuff Decreased insulin sensitivity? Decreased insulin secretion? (Cederberg Diabetologia 2015 cohort study) Familial hypercholesterolemia: lower DM risk (Besseling JAMA 2015)

106 Do statins cause memory problems?

107 Do statins cause memory problems? Maybe Case reports FDA warning Memory loss / confusion Reversible if stop the drug

108 What about lifestyle measures? Yes, for everyone (of course!)

109 What about non-statin drugs?

110 What about non-statin drugs? VERY little positive RCT data for any of them Some very old data for fibrates, before the modern statin era Niacin data not beneficial (AIM-HIGH, HPS-2)

111 How do I discuss whether to take a statin with patients?

112 How do I discuss whether Language: to take a statin with patients? Match your level of concern with the patient s risk I strongly recommend This is an optional, additional way to lower risk Decision aids? (for visual learners)

113 How do I discuss whether Language: to take a statin with patients? Match your level of concern with the patient s risk I strongly recommend This is an optional, additional way to lower risk Decision aids? (for visual learners)

114 How do I discuss whether to take a statin with patients? Make it part of overall cardiovascular risk assessment: Weight, exercise, diet, blood pressure, smoking, family history... What the patient can change Optional meds to lower risk further: Aspirin, statin (is it worth it to the patient?)

115 Summary Many good things about the new guidelines: LDL targets never made much sense. Moving away from that is good. 4 risk categories: clinical CV disease, LDL > 190, DM, risk 7.5%

116 Summary But: Still seem to advocate rechecking lipids more often than is probably needed Is quite aggressive with high intensity recs Most older men will meet threshold We need the right language for shared decision making do NOT just calculate 7.5% and start a statin!

117 Summary But: And... Still seem to advocate rechecking lipids more Is often the treatment than is probably worth it: needed worth the potential side effects Is quite or aggressive other downsides with high such intensity as cost, recs inconvenience, Most older men etc? will meet threshold We need the right language for shared Make decision lipids making do part of overall NOT cardiovascular just calculate risk discussion 7.5% and start a statin!

118 In the end it s the same questions How much risk? How much treatment?

119 Thank you! questions