10 things to do until atp iv is released - canpcanpweb.org/canp/assets/file/2013 conference...
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2006 AHA Recommends LDL < 70 as reasonable target for secondary
prevention Gender specific HDL targets. Men > 40, Women > 50
JUPITER trial: Benefit for statins in primary prevention, women and patients > 70 years
Metabolic syndrome = HIGH RISK SHARP trial: Statins benefit chronic kidney
disease HPS2 Thrive and AIM HIGH trials
The Critical Questions What evidence supports LDL goals for secondary
prevention? What evidence supports LDL goals for primary
prevention? What is the efficacy and safety of major cholesterol
drugs? Risk assessment tools Alternative treatment targets: APO B, Non-HDL Role of fibrates, niacin, ezetimibe, BAS
What is her risk of future cardiovascular disease? 56 y.o. female Former smoker Sister with ischemic stroke age 54 No family premature coronary artery disease BP138/76 Fasting glucose 109 Total cholesterol 209 HDL 42 Triglycerides 201 BMI 31
Risk Score Estimated Risk Framingham 2% Reynolds 6% Global CVD 10% QRISK 11% Lifetime Risk 39%
Berger. JACC. 2010; 55: 1169-1177.
Access at www.reynoldsriskscore.org
Wickramasinghe, R. Am J Cardio. 2009;103: 1174-1177
Use a coronary calcium score to reclassify patients with intermediate risk. DO reserve CAC testing for patients where results will likely alter management. DO discuss the CAC score in a way that is meaningful for patients DO encourage patients to pursue ideal cardiovascular health even if their score is 0 Do discuss the risk of radiation.
Polonsky,T. Cardiol Clin 30 (2012) 49-55Us
DON’t use to screen patients with symptoms of CAD
DON’T use to follow progression of CAC DON’T use to monitor lipid therapy DON’T use the CAC as an indication for
coronary angiogram
Polonsky,T. Cardiol Clin 30 (2012) 49-55.
Begin with a frank discussion
If BMI >26 recommend weight loss. Low CHO diet best for triglyceride ↓ and
HDL ↑ Lower HDL and triglycerides independent of
weight loss at 6 and 12 months. Atkins 18%↑ HDL, 28% ↓ in triglycerides. Similar to niacin and fibrates.
No change in LDL
Parik,P. JACC 2005 45:9. 1380-2387.
All diets increased HDL and reduced triglycerides
Biggest HDL increase with low carbohydrate diet. 9%
All diets reduced triglycerides 12-17%. How much weight loss? (5-10% of body weight)
Low fat diet reduced LDL 5% High protein lowered insulin levels 12%.
Insulin resistance is a cardiovascular risk factor
Sacks. NEJM 2009;360:859-873
Mediterranean diet reduces heart attack, death and stroke by 28-30% in high risk patients
What did they eat? Fish 3 times/week Beans 3 times/week Olive oil 4 tablespoons/day or 1 ounce walnuts/day 3 fruits a day (minimum) 2 vegetables a day (minimum) No red meat No commercially prepared cakes, cookies or pastries Limit dairy, processed meats 7 glasses of wine per week (if desired)
DOI: 10.1056/NEJMoa1200303 Feb. 23, 2013
AHA Recommends 150 minutes of moderate exercise/week “30 minutes/5 days per week”
Try a Pedometer 3000 steps in 30 minutes is moderate exercise 10,000 steps per day = Weight Loss
3 Grams of soluble fiber lowers LDL 2% 1 TBS = 2 grams soluble fiber 1 c. cooked Steel cut oats = 2 gm soluble fiber 1 apple = 1 gram soluble fiber
1. Recommend as part of the TLC diet 2. 1800 mg plant stanols daily 3. 9.2% LDL lowering 4. 9 % non-HDL lowering 5. No effect on HDL or triglycerides
Benechol Chews Heartwise Rice Milk Benechol Margarine Cholestoff
Maki,K.C. Nutrition 29:1 2013 (96-100)
Martin et al, Am J Cardiol 2012;110:307–313
Lloyd-Jones, D Circulation. 2010;121:586-613
High 10 Year Risk LDL < 7
High Lifetime Risk
LDL < 100
Low Risk LDL <115
O’Keefe. JACC 43:11(2004) 2142-2146
O’Keefe. JACC 43:11(2004) 2142-2146
My LDL GOAL ______ Current LDL ______ CHANGE LDL LOWERING Lose 10 lb. 5-8% Saturated Fat < 7% 8-10% 10 gm. Soluble Fiber/day 3- 5% Plant Stanols 1800 mg/day 5-10%___ TOTAL LDL LOWERING 20-30%
Martin et al. Am J Cardiol 2012;110:307–313.
Prescriber's Letter 2011;18(11):27112
50% still taking statins at 6 months Only 25% at 1 year Explain why you’ve chosen statin therapy Review risk assessment tool results Explain the plan Discuss side effects clearly Question specifically about aches before
starting a statin 8 week, 6 and 12 month followup visits
JUPITER showed ↑ risk of developing new onset diabetes (NOD) if risk factors present
2-4 risk factors for DM→ 14% NOD on atorvastatin 80 mg. FBG > 100 Fasting triglycerides > 150 BMI > 30 Hypertension
Waters, D. JACC 2013 61:2. 148-152.
FDA added Safety Label change Feb 2012 Can occur days to years after starting statins Average time to improvement after
discontinuing statin: 3 weeks Symptoms: Confusion, memory impairment,
amnesia
Bardwaj, S. Clinical Interventions in Aging 2013:8 47–59
Myalgia: Muscle soreness or weakness Myopathy: CK > 10,000 Rhabdomyolosis:
CK > 10,000 Worsening renal function Requiring IV hydration
McKinney, J. Am J Cardiol 2006;97[suppl]:89C–94C
Arca,M. Diab Metab Syndr Obes. 2011:4.155
Female Polypharmacy Vigorous exerciser Age > 80 Low BMI Drug-drug interaction Post major surgery/trauma Comorbidities (Diabetes, hypothyroidism) Genetic predisposition Vitamin D deficiency (<32)
Non-absorbed bile acid sequestrant (BAS) Safe in children > 10 years LDL lowering 18% Add on to statin or use in statin intolerance Contraindicated triglycerides > 500 Hgb A1c lowering of .5% or 14 points fasting
glucose Caution: take phenytoin, glyburide, OCP,
cyclosporine, levothyroxine, warfarin 4 hours prior
Non-HDL, APO B and LDL particle number important in patients with mixed hyperlipidemia, MetS, Type II DM and CKD
High 10 Year Risk Non HDL < 100, Apo B < 80
High Lifetime Risk Non HDL < 130, Apo B < 100
Total cholesterol minus HDL Example: 240 – 40 = 200 Non-HDL Cholesterol
Use when triglycerides are elevated. Advantage: No cost, measure non-fasting Better marker than LDL for atherogenic small
particles Likely to be included in ATP IV
Non HDL goal: LDL + 30
o
Otvos. Am J Cardio 2002; 90:8A. 22-29
Add-on to statins. Beneficial in MetS, DM, BMI > 26 LDL increase if triglycerides above 500 Caution: warfarin interaction with increased INR ↑creatinine occurs with fenofibrate. Lipid effects:
↓ Trig 35-50% ↓ LDL III 27% ↑ HDL 15-25% ↑ HS CRP 15-20%
Reduces triglyceride production New purified pharmaceutical brands (1860
mg EPA) 4 grams = 44 calories Possible prolonged bleeding time Lipid effects:
↓ triglycerides 26-47% ↑ LDL 10-47% ↑ HDL 11-14%
Niacin. Is there outcomes data? AIM-HIGH Heart Protection 2
Adding ER niacin/laropriprant to simvastatin did not significantly reduce risk of MI, CVA or angioplasty in secondary prevention
↓ LDL 10 mg, ↓triglycerides 33 mg, ↑HDL 6 mg Significant adverse effects: diabetic
complication, new onset DM, GI complications and bleeding, pneumonia (30 patients 1000)
Conclusion: “role of ER niacin needs to be reconsidered”
Statins and the Elderly Heart Protection Study: 25% reduction of
stroke, any age PROSPER. 20% reduction death from
CAD/MI. Men and women, average age 75 yrs. Frail elderly more likely to have myopathy
Lipid abnormalities with HIV ↓ LDL, ↓ HDL, ↑ Trig
Lipid effect of Protease inhibitors 28%↑ TC, 96% ↑ Trig
Treat with statins/fibrates/fish oil Statin, antiretroviral interaction Caution ritonavir, azoles, macrolides Use rosuvastatin , pravastatin, fluvastatin Ezetimibe is safe Niacin may worsen insulin resistance
Gutierrez. Arch Int Med. 2012;(172)12:909-919.
TC, LDL and triglycerides increase 20-35% in pregnancy
Colesevelam pregnancy category B, can be taken by nursing mothers
Statins pregnancy category X May inhibit placenta and embryo
growth Ezetimibe pregnancy category C Fenofibrate pregnancy category C
1. NKF: CKD Stages 3-5 is a coronary risk equivalent 2. Lipid abnormalities similar to Metabolic syndrome
1. Low HDL 2. Small, dense LDL 3. Elevated LDL particle number 4. Elevated triglycerides LDL goal 70 Calculate non-HDL C Use statins. They reduce CV events in Stage 3 and 4 CKD Safest statins—atorvastatin, simvastatin, fluvastatin. ↓ dose
risk of myopathy SHARP trial simvastatin and ezetimibe reduced CV events Fenofibrates. Dose reduction 50% if GFR 60-90, 75% if GFR
15-60. Will raise serum creatinine. NKF recommends gemfibrozil
LDL goal 70 Calculate non-HDL C. Goal 100 SHARP trial (simvastatin + ezetimibe) 17%
reduction in CV events Safest statins—atorvastatin, simvastatin,
fluvastatin. ↓ dose risk of myopathy Fenofibrates. Dose reduction 50% if GFR
60-90, 75% if GFR 15-60. Will raise serum creatinine. NKF recommends gemfibrozil
Decrease cholesterol absorption in the intestine and upregulates LDL receptors
Add on to statins or monotherapy LDL↓ 27% added to statin LDL ↓ 18% as monotherapy Lowers Non-HDL and Apo B Outcomes data? Side effect: Diarrhea. Rare myalgia, myopathy
or elevated ALT/AST
FDA no longer recommends routine liver function testing with statins. Baseline liver function testing only.
Repeat lipid panel as early as 6 weeks Appropriate to delay lipid panel for 3 to 4
months if more convenient
1. Assess risk accurately 2. Use a simplified treatment algorithm. 3. Start lifestyle changes at the first visit. 4. Recommend a mediterranean diet 5. Promote ideal cardiovascular health 6. Establish an LDL goal of <70 for high risk 7. Write out a lipid plan. 8. Use statins for high risk 9. Look at targets beyond LDL 10. Follow up at appropriate intervals