9/3/ AHA/ACC Lipid Guidelines on the Treatment of Cholesterol to Reduce Atherosclerosis. Disclosure

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1 2013 AHA/ACC Lipid Guidelines on the Treatment of Cholesterol to Reduce Atherosclerosis Robert Gleeson MD Preven5ve Cardiology and Lipid Management Froedtert and The Medical College of Wisconsin Disclosure Co- owner, Prevent CVD Publishing Author Lipidology, A Primer, the what, why, and how of beker lipid management Unless otherwise noted, all slides are taken or adopted from: 1

2 2013 ACC/AHA Guidelines 1. Focus on ASCVD Reduc5on 2. Require RTC evidence 3. Promote a heart healthful lifestyle for all pa5ents 4. Simplify treatment decision 5. Focus on correct sta5n dose (not on LDL goals) 6. Add pooled cohort calculator for lower risk groups 7. Add biomarkers and noninvasive tests to improve risk classifica5on 8. Give safety recommenda5ons The findings support the use of sta5ns to prevent both nonfatal and fatal ASCVD events. Such an approach can reduce the large burden of disability from nonfatal stroke (for which women are at higher risk than men) and nonfatal CHD events. Primary and secondary preven5on of ASCVD with sta5ns can posi5vely impact rising healthcare costs. A high level of evidence was found that sta5ns reduce total mortality in individuals with a history of prior ASCVD events (e.g., secondary preven5on sezngs). In individuals with no prior history of ASCVD events (e.g., primary preven5on sezng), there is moderate evidence that sta5ns reduce total mortality in individuals at increased ASCVD risk. It should be noted, 2 meta- analyses published a\er the comple5on of the Expert Panel s systema5c review provide strong evidence that sta5ns reduce total mortality in primary preven5on (12,13). Stone et al Circ Nov 2013 p ACC/AHA Expert Panel Found RCT evidence that the appropriate dose and intensity of sta5n should be used to reduce ASCVD risk in those most likely to benefit addi5onal lipid- modula5ng therapy (e.g, niacin) did not further reduce ASCVD risk when added to a sta5n Found no benefit in heart failure NYHA class II to IV or maintenance dialysis Emphasized lifestyle at all stages and treatments 2

3 ACC/AHA Expert Panel Review of RTC The cholesterol- lowering guidelines therefore retain LDL- C as the primary target for lipid modifica5on, and sta5n therapy as the primary means of achieving LDL- C goals. Why just sta5ns? Cholesterol Treatment Trialists Lancet Nov 2010 In all subgroups, when statins lower LDL 1 mmol, they lower ASCVD events by 25% Lancet Nov

4 Reduction in CV events by statins is independent of baseline LDL Lancet Nov Cochrane Review (18 RTCs, N = 56, 394) of statins Risk Reduction Based on Absolute ASCVD Risk NNT to Prevent 1 80 Event over years year CVD Risk 4

5 Risk Reduction Based on Absolute ASCVD Risk Using Moderate-Dose Statins NNT to Prevent 1 80 Event over years % cut- point year CVD Risk Take home: Benefit is propor5onal to the absolute risk of ASCVD Risk Reduction Based on Absolute ASCVD Risk NNT to Prevent 1 80 Event over years year CVD Risk NNH (new diabetes) 2013 ACC/AHA guidelines simplify treatment decisions Define risk High risk Moderate risk à treat accordingly à high dose of high- intensity sta5ns à moderate- intensity sta5n Others à Pooled Cohort Risk Calculator > 7.5% discuss Rx with sta5ns 5% to 7.5% consider alterna5ve tests < 5% repeat calculator in 5 years No LDL targets Only sta5ns show 1 o and 2 nd benefit 5

6 Four major groups with proven benefit from stacn use Use high- intensity high- dose stacns (LDL lowering < 50% ) 1. Individuals < 75 yrs with clinical ASCVD and LDL 70 to 189 Atorvasta5n 40 or Individuals < 75 yrs with LDL > Rosuvasta5n 20 or Use moderate- dose stacns (LDL lowering 30% to 50%) 3. Diabe5cs age 40 to 75 who do not have ASCVD with LDL 70 to Individuals age 40 t0 75 without ASCVD but with 10- year risk > 7.5% and LDL 70 to 189 Atorvasta5n 10 or 20 Fluvasta5n 40 Fluvasta5n XL 80 Lovasta5n 40 Pitavasta5n 2 to 4 Pravasta5n 40 to 80 Rosuvasta5n 5 to 10 Simvasta5n 20 to 40 New versus old guideline in action 55- yo with recent angina treated with stent Star5ng lipids: TC 143 Trig 160 HDL 32 LDL 80 ATP said treat with sta5n to get LDL < 70 so simvasta5n 20 was adequate TC 124 Trig 120 HDL 34 LDL ACC/AHA say to treat with high- dose of high intensity sta5n for > 50% LDL lowering will maximally lower risk Trea5ng with atorvasta5n 40 or rosuva 20 TC 87 Trig 80 HDL 36 LDL 35 This is OK and by guideline lowers ASCVD risk Use high-dose of high-intensity statins Stone et all, Circ Nov 2013 p 15 6

7 Use moderate-dose statin Patients with LDL > 190 (e,g, Familial Hypercholesterolemia) 1. Use high- dose of high- intensity sta5ns to reduce LDL by > 50% 2. Maximum sta5n therapy may not reduce LDL sufficiently to reduce risk and [addi5onal] non- sta5n cholesterol- lowering medica5ons may be needed to achieve acceptable levels in these individuals (Stone et al, Circ 2013, p. 29) 3. These pa5ents should be counseled about the importance of family tes5ng Age 40 to 75, Primary Prevention No ASCVD, no diabetes, LDL

8 Pooled Cohort Risk Calculator If 10- year risk > 7.5% à treat with moderate sta5n If risk 5% to 7.5% Reasonable to treat if Family history of premature ASCVD CAC > 75 th percen5le for age or score > 300 LDL > 160 hscrp > 2 ABI < 0.9 8

9 If risk 5% to 7.5% Reasonable to treat if Family history of premature ASCVD CAC > 75 th percen5le for age or score > 300 LDL > 160 hscrp > 2 ABI < 0.9 9

10 CAC score percentiles for men by age Treat if > 75 th percentile or > 300 %tile Age Men < > 75 25th th th th Huff JA Am J. Card 2001;87: CAC score percentiles for women by age Treat if > 75 th percentile or > 300 %tile Age Women < > 75 25th th th th Huff JA Am J. Card 2001;87:

11 CAD Rates by CAC Score 4 Annual CAD Event Rate to to CAC score DM MetS Neither MetS or DM ACCF/AHA 2010 Guideline Unadjusted Kaplan Meier for any coronary events by CAC score Detrano, et al. NEJM 2008;358:1336 Initial evaluation Before star5ng sta5n Fas5ng* lipid panel * Non- fas5ng is beker than no lipid panel Use non- HDL ALT* * Some prefer AST CK if indicated by history if LDL > 190, evaluate for FH and secondary causes Document pre- sta5n myalgias (not in guideline) Evaluate and treat first Trigs > 500 ALT > 3 x nl 11

12 Initiating therapy step 2 The focus is on risk groups, not LDL target Expert panel did not find evidence supporting LDL targets Treat to New Targets studied benefit of atorva 10 vs atorva 80. TNT did not study whether getting LDL < 70 provided more benefit than an LDL of < 100 Did find studies showing the addition of meds to further LDL did not take adverse effects into account Conclusion: Use of LDL-C targets may result in undertreatment with evidence based statin Rx, or over therapy with non-statin drugs that have not been shown to reduce ASCVD events in RCT s Nonetheless and not in guideline Targets are useful Help our pa5ents have a goal Keep providers mindful Are supported by Cholesterol Treatment Trialists meta- analysis showing that lower is beker 12

13 Causes of elevated LDL (table 6) Monitoring statin therapy Measure lipids 4 to 12 weeks a\er star5ng RX Then every 3 to 12 months If high- risk and inadequate response, consider adding addi5on RX Statin safety Myalgias Myalgias are real and may bother 5% to 10% of pa5ents Recommend: ask pa5ents to iden5fy their muscle and joint aches for the 2 weeks before sta5ns started. Then start the sta5n. When they complain of myalgias, compare the two. Can o\en con5nue the sta5n, which will lower their risk of ASCVD 13

14 Statin safety -- measuring CK CK should not be rou5nely measured in individuals receiving sta5n therapy Baseline CK is reasonable to measure in pa5ents believed to be at increased risk for adverse muscle events During sta5n therapy, it is reasonable to measure CK in pa5ents with muscle symptoms Statin safety measuring LFTs Baseline measurement of ALT should be performed before star5ng sta5n therapy If ALT > 3 x, then hold sta5n and inves5gate During sta5n therapy, it is reasonable to measure ALT if symptoms suggest hepatotoxicity Statin safety Decreasing the sta5n dose may be considered when 2 consecu5ve LDL < 40 (1 mmol) During sta5n therapy, it is reasonable to check for diabetes by normal guideline. If diabetes, then emphasize lifestyle to reduce their risk of ASCVD Sta5ns are category X for pregnancy 14

15 Statin monitoring A\er star5ng sta5n therapy, check LDL at 4 to 12 weeks a\er ini5a5on for side effects and efficacy of sta5n therapy Then at 3 to 12 months as indicated Lifestyle is the cornerstone of prevention Lifestyle reduces CVD risk by 30% in most pa5ents The greatest benefit is a life5me of heart- healthful behaviors Having optimal CV risk factor profile confers a very low lifetime risk of CVD Never smoking BP < 120/80 LDL, and HDL > BMI < 25 No diabetes Being ac5ve Mediterranean diet 15

16 Important points to remember Most CAD happens in pa5ents with average CV risk factors Early treatment before disease appears has proven benefit WOSCOPS, ASCOT- LA, CARDS, MEGA, AFCAPS/TexCAPS, and JUPITER primary preven5on pa5ents enrolled between 1995 and 2008 Cholesterol- lowering with sta5ns reduces events 20% for every 40 mg of LDL lowering There is no lower LDL limit of benefit Limitations and questions of the 2013 ACC/AHA Guidelines Expert panel used mainly RCT from 2005 to 2010 If niacin is not helpful in patients with CAD and controlled LDL and Non-HDL, is it beneficial in other populations (e.g., metabolic syndrome) Do fibrates help in patients with HDL < 35 and trigs > 200 as shown in post-hoc analysis of fibrate studies? What if ezetimibe is found beneficial in the pending IMPROVE-IT trial? If currently on statin and LDL < 100, do higher statin doses make a material difference? Future steps ACC/AHA have a pre- specified guideline template These guidelines do not follow that template The ACC/AHA guideline commikee will likely re- convene to rewrite them within 3 years Likely to follow current focus Triglyceride disorders likely le\ to endocrine guideline panels 16

17 Guidelines attempt 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. 17