Update on Atherosclerosis Treatment and Prevention Ronald D. Scott, MD Lipidology and Family Medicine West LA Med Center Regional CVD Colead Overview Lipids and CAD risk CVD is major killer and impacts morbidity Large statin benefit opportunity Treat high LDL (> 190) regardless of risk. Treat those at risk, regardless of LDL (>70) Optimizing Performance Identifying patients STAtin: Starts, Titrations, and Adherence Use tools to promote statins Safety / intolerance of statins Beyond statins 1
Also, stroke is #3 cause of mortality and much feared, significant morbidity. Heart disease and stroke are very costly. Risk factor INTER-HEART: MI risk PAR adjusted for age, sex, and smoking (99% CI) Yusuf S. European Society of Cardiology Congress 2004 PAR adjusted for all (99% CI) ApoB/ApoA-1 (fifth 54.1 (49.6-58.6) 49.2 (43.8-54.5) quintile compared with first) Current smoking 36.4 (33.9-39.0) 35.7 (32.5-39.1) Diabetes 12.3 (11.2-13.5) 9.9 (8.5-11.5) Hypertension 23.4 (21.7-25.1) 17.9 (15.7-20.4) Abdominal obesity 33.7 (30.2-37.4) 20.1 (15.3-26.0) Psychosocial 28.8 (22.6-35.8) 32.5 (25.1-40.8) Vegetable and fruits 12.9 (10.0-16.6) 13.7 (9.9-18.6) daily Exercise 25.5 (20.1-31.8) 12.2 (5.5-25.1) Alcohol intake 13.9 (9.3-20.2) 6.7 (2.0-20.2) All combined 90.4 (88.1-92.4) 90.4 (88.1-92.4) 2
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Last LDL > 190 in KPSC 33,000 KP So Cal members. If lifestyle not successful, statins recommended if age > 10 years old. Easy to tell in inbox if patient needs statin by this criteria. Is regardless of risk. For adults, lower LDL at least 50%. Start atorvastatin 80 mg daily (53% LDL lowering) Protective PCSK9 mutations Lifelong decreased levels of LDL. Variant 1: 28% reduced LDL 88% reduction in CAD. Variant 2: 15% reduced LDL 50% reduction in CAD. Event reduction impressive: favorable impact of low cholesterol over a long time 4
Risk in Primary Prevention Trials 10 y risk 5.0 % 7.5% 5
avg A-risk of 7.5 % Entry LDL<130, mean 105 avg FRS of 12% Entry LDL<130, mean 105 6
Large statin benefit +/- disease (including Primary Prevention) Primary prevention Lancet Nov 9, 2010 Statins benefit across age span - including those over age 75 CCT. Lancet Nov 9, 2010 7
Statins benefit across range of baseline lipids Baseline LDL mg/dl <76 77-96 97-116 117-136 > 135 LDL 150 to 89 same benefit as LDL 77 to 45 Lancet Nov 9, 2010 HPS: NNT NNT (simvastatin 40 mg) to prevent one MI, stroke or revascularization in 5 years. DX NNT Post MI 10 Angina 12.5 s/p Stroke, PAD, DM age > 40 14 Young DM with 80% Lifetime risk of CAD Simvastatin 40 mg in Heart Protection Study 2001 8
JUPITER: NNT Statin risks, NNH NNH of new onset DM, myopathy. Conservative estimates. Harm not as severe as MI or stroke. Low to Moderate intensity statin (< atorvastatin 20 mg) 6 excess cases of adverse effects per 1000 statintreated persons over 5 years NNH = 167 High intensity statin (atorvastatin 40-80 mg) 16 excess cases of adverse effects per 1000 statintreated persons over 5 years NNH = 63 9
Starting Statins Acute Ischemic Stroke / Acute Coronary Syndrome: atorvastatin 80 mg LDL > 190 (regardless of risk): atorvastatin 80 mg CAD / IVD, DM (age > 40 or RF), or FRS > 10%: atorvastatin 40 mg simvastatin 40 mg for cost sensitive members with higher atorvastatin copayments Consider lower doses, clinical judgment and / or shared decision making in patients with: baseline LDL < 70, Age > 76 years, Liver disease or muscle disorders. Asian ancestry. % on statin CAD/IVD. In last 6 mos 84% DM age > 40. In last 6 mos 76% LDL > 190. ever on statins 66% FRS > 10%. About 30% Need about 500,000 statin starts 10
Generic statins are cost saving in lower risk primary prevention High intensity statin over 10 years is cost saving vs low/moderate intensity statin with > 2.5% 10-year CVD risk Generic statins cost saving with > 5% 10- year CHD risk Pletcher MJ, et al. Ann Intern Med. 2009;150:243-254; Heart Protection Study Collaborative G. Circ Cardiovasc Qual Outcomes. 2009;2(2):65-72; Conly J, et al. Can Med Assoc J. 2011;183(16):E1180-E1188. FRS > 20% FRS 15% With revised guidelines, FRS>10% (and more) in statin target population. Large population with large treatment potential 11
STAtins - key to lipid control Start statins in the untreated Titrate up on the undertreated Adherence promotion / working barriers 12
Finding the inclusion code: IVD Ischemic Vascular Disease CAD: post MI, post CABG, post PCTA, angina. Status post stroke, carotid artery occlusion. Peripheral arterial disease, AAA. NOT include aortic atherosclerosis, aortic ectasia. 13
Abdominal Aorta Screening Abdominal Aortic Aneurysm (AAA) is considered CAD risk equivalent by NHLBI / ATP and KP guidelines statins and LDL < 100 control recommended. Is part of our CAD POINT registry for targeting. Aortic Screening Rate Trend 17% increase in region so far! 28 14
Diagnosis and Actions by Aortic Diameter < 2.4 cm: Normal diameter. (check for aortic athero) 2.5-2.9 cm: Aortic Ectasia, place on problem list. Start statin if FRS > 10%. > 3.0 cm: Abdominal Aortic Aneurysm (AAA), start statin, code and place on problem list. > 4.0 cm: above actions, plus referral to vascular surgery. Aortic Ectasia. 2.5-2.9 cm Risk Hazard Ratio (crude) Acute MI 1.60 (1.07 2.37) Stroke 1.59 (1.16 2.18) Heart Failure 1.85 (1.39 2.46) Total Mortality 1.46 (1.05 2.02) Vascular Mortality 1.77 (1.20 2.63) Duncan JL et al. BMJ 2012 May 4; 344:e2958 30 15
Aortic Atherosclerosis and Aortic Ectasia Although not automatic risk equivalents, are markers of increased risk. Imaging findings show risk to patient. Revenue for KP. Patients more likely to have annual appointments. Imaging results can be used as opportunity to promote cardiovascular health. Positive imaging findings communicated with patients leads to higher statin and aspirin use (OR 7.0) J Am Coll Cardiol Apr 2008 Available to members with data elements Start atorvastatin 40 mg daily Framingham risk score (FRS) calculator. Expanding availability. Will change to A-risk in 2013. 16
"Pre-statin" and latest FRS are calculated and shown above. FRS > 10 %: start atorvastatin 40 mg FRS > 15% (or on treatment > 10 %): start aspirin 81 mg daily at kp.org for members 17
Artery image in-person patient education. Tear-off pads or posters, English or Spanish, illiterate. Order from Health Education and use in exam rooms. to reduce cholesterol, heart attacks and strokes in sig Smart Rx - Lipids 18
Titration Titration Table lovastatin or pravastatin dose Treated LDL-C level Change to: <= 20 mg 100-129 atorvastatin 40 mg <= 20 mg > 129 atorvastatin 80 mg 40 mg 100-119 atorvastatin 40 mg 40 mg >119 atorvastatin 80 mg 80 mg 100-109 atorvastatin 40 mg 80 mg >109 atorvastatin 80 mg simvastatin dose Treated LDL-C level Change to: <=10 mg 100-129 atorvastatin 40 mg <=10 mg >129 atorvastatin 80 mg 20 mg 100-119 atorvastatin 40 mg 20 mg >119 atorvastatin 80 mg 40 mg 100-109 atorvastatin 40 mg 40 mg >109 atorvastatin 80 mg 80 mg >99 atorvastatin 80 mg atorvastatin dose Treated LDL-C level Change to: < = 10 mg 100-119 atorvastatin 40 mg < = 10 mg >119 atorvastatin 80 mg 20 mg 100-109 atorvastatin 40 mg 20 mg >109 atorvastatin 80 mg 40 mg >99 atorvastatin 80 mg 19
Encouraging Letter Safety, intolerance and barriers 20
Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study Lancet Nov 24, 2010 Increased baseline ALT increased statin benefit? GREACE study: rrr of recurrent cardiovascular event Elevated liver tests NAFLD: 68% Normal liver function: 39% Consistent with other studies that those with NAFLD and steatohepatitis are at higher CV risk and may benefit more from statins. The FDA statin labeling change 2/28/12 revised to remove the need for routine periodic monitoring of liver enzymes. 21
Rosuvastatin risk of new DM JUPITER rosuvastatin 20 mg daily: In those without RF for DM: 86 CV events prevented, and 0 cases of increased DM. In those with RF for DM: 134 CV events prevented (MI stroke, death) and 54 new cases of DM. (28% increase) 40 day acceleration of progression to DM. Compare to 55% reduced MI, 44% reduced combined endpoint, 20% lower mortality. DM risk drives NNH estimate of 63- Lancet 2012; 380: 565-571. Atorvastatin risk of new DM Atorvastatin 80 mg overall OR 1.15 of New DM RF: FBS > 100, TG > 150, BMI > 30, HTN JACC, Jan 2013. Am J Car, Jan 2013 22
statin muscle issues Risk Factors: interacting meds, statin dose relative to max, older age, female, cirrhosis... Check and treat high TSH (hypothyroid) before starting therapy. If muscle symptoms, double check if recent TSH. Consider treating low vitamin D. About 90% resolution of myopathy in 3 small studies. CoQ10, creatine,...? Muscle Risk lova simva prava rosuva atorva % LDL 20 mg 10 mg 20 mg ----- ----- 27% 40 mg 20 mg 40 mg ----- 10 mg 34% 80 mg 40 mg 80 mg 5 mg 20 mg 41% ----- 80 mg ----- 10 mg 40 mg 48% ----- ----- ----- 20 mg 80 mg 53% ----- ----- ----- 40 mg 58% Adapted from SLCO1B1 in Clin Pharm Ther. 2009;87(1):130-3 And FDA potency table 23
Muscle SE - options Low dose statin (relative to max) often with better tolerance. atorvastatin 10 mg daily 34% lowering. rosuvastatin 5 mg daily 41% lowering. If still not tolerating decrease frequency to 1-2 x a week atorvastatin or rosuvastatin most studied and long acting. If not tolerate multiple statins, red yeast rice? Red Yeast Rice has issues Arch Intern Med Oct 2010 24
If non adherent, ask is cost a barrier? MFA program for patients that qualify. Mail order pharmacy incentive (3 months for cost of 2) Some Commercial Plans: Atorvastatin is not on KP CA Preventive Care Drug list, resulting in more copays and cost sharing than other generic statins. Medicare Senior Advantage Individual Plan patients make up 50% o our Medicare (age>65) patients. Tier 1 copay: $ 6 for 100 day supply with Mail Order. Simvastatin, lovastatin. Tier 2 copay: $ 14 for 100 day supply with Mail Order. Atorvastatin, pravastatin. Beyond Statins Priority is to optimize statin first, before going beyond statins to other lipid treatments. cost/yr % LDL atorvastatin 10 mg $ 34 % Red yeast rice $$ 17 % Add On Therapies ezetimibe 10 ½ tab $$$ (brand) 12 % Stanol Chews $$$ (OTC) 5-9 % Or sterols $$ (OTC) 9 % Bile acid sequest $$$ (gen) 10 % slo-niacin 500 bid $ (OTC) 5 % Factors to consider: tolerability, patient preference, cost, desired lipid changes, outcome evidence. 25
Ezetimibe (Zetia) Well tolerated, moves LDL well. Mixed results in imaging studies. Simvastatin / ezetimibe seemed to reduce events similar to equipotent statins in SHARP study. Await better event outcome data comparing statin alone to statin + ezetimibe (IMPROVE-IT). Brand cost about $500/yr (for ½ tab). Cost to pt depends on drug benefit. Plant Stanols / sterols 2 chews BID, $300/yr LDL 9% 1 chew BID, $150/yr, LDL 5%. 2 caps BID, $95/yr, LDL 9% NIH recommends 2 g daily. Dietary source is fat rich vegetables, fruits, and nuts Avg American gets 0.2 g daily Should not use in sitosterolemia - where pts get. xanthomas and CAD from inability to process plant stanols 26
Bile Acid Sequestrants (BAS) Lowers LDL about 23% (monotherapy) Favorable mono and combo outcome studies. Cholestyramine powder (Questran), 1 scoop BID: $300 Colestipol powder or tab bid: $500 Colesevalam (Welchol) bid: > $2000 / yr SE: Constipation, dyspepsia, can raise elevated TG, interferes with absorption of other meds (need to space timing). Slo-Niacin Slo-Niacin 500 mg bid LDL 5%, HDL 15% $ 51 / y Contraindicated with liver disease and active peptic ulcer disease. Glucose, uric acid Monotherapy studies benefit. Add on to statin no benefit in AIM-HIGH and HPS2-THRIVE Slo-Niacin 500 mg scored tabs ½ tab after dinner for 1 week, ½ tab bid for 1 week, then 1 tab po bid from then on. Time after dinner to decrease flushing. Flushing wanes over 2-3 months. 27
TG Therapy TG Guidance When statin indicated 1. If indication for statin, start statin. Statins are priority and can lower TG 20-30%. If TG are still > 200, 2. optimize potential contributing factors (hyperglycemia, excess alcohol, hypothyroid, obesity, medicines) and lifestyle interventions. If TG are still > 500, 3. Add/ or increase Omega-3 to 3-4 g daily and retest. If TG still > 500, then: consider add niacin consider intensify atorvastatin consider adding fenofibrate GFR > 30, use with sub-maximal dose statin 28
Both KP and Costco Omege 3 have 684 mg per softgel. (6 to 8 cents each) 5 caps / day = 3420 mg of Omega 3 for $110 / year. Diabetes: meds 4 CV reduction Screening: Hgb A1C > 6.5, Fasting Glucose > 126, 2 hr glu > 200. 2+ ever. Metformin: Titrate up to 1000 mg bid right away, CV benefits. GFR 30-59 use 500 bid. Statin: HEDIS measures performance in all DM. Guidelines rec: DM age > 40 or age < 40 with RF. Young DM with 80% lifetime CV risk. Aspirin 81 mg daily if 10 yr risk > 10% Men age 50-64 with RF, all age 65-85. Women age 60-85 with RF. Lisinopril 20 mg for MA, HTN, or age > 55 with RF 29
Overview Lipids and CAD risk CVD is major killer and impacts morbidity Large statin benefit opportunity Treat high LDL (> 190) regardless of risk. Treat those at risk, regardless of LDL (>70) Optimizing Performance Identifying patients STAtin: Starts, Titrations, and Adherence Use tools to promote statins Safety / intolerance of statins Beyond statins Use tools and prevention to improve outcomes Use tools and prevention: integrated data / IT proactive care, CMSS, HC Artery graphic, patient relationship, clinical skill teamwork (care managers) Inexpensive generic atorvastatin, aspirin. To improve outcomes: Reduced CVD morbidity / mortality. Reduce costly CVD procedures, hospitalizations, and morbidity care. Better quality performance. Financial rewards for KP and for providers. 30
Question In JUPITER, rosuvastatin (Crestor) 20 mg (lowered LDL 50%) showed risk reduction of MI, and of combined endpoint of MI, stroke, revascularization, CV death of: A) MI 55% and combined endpoint 44%. B) MI 50% and combined endpoint 40%. C) MI 44% and combined endpoint 33%. 31