Nicole Ciffone, MS, ANP-C, AACC Clinical Lipid Specialist

Transcription

1 1 Nicole Ciffone, MS, ANP-C, AACC Clinical Lipid Specialist New Cardiovascular Horizons Multidisciplinary Strategies for Optimal Cardiovascular Care February 7, 2015

2 2 Objectives After participating in this activity the audience will be able to: Discuss recent released guidelines for cholesterol management Identify individuals that would benefit from treatment with statins Prescribe appropriate intensity of statin based on an individuals risk category Identify individuals who may have residual risk that requires additional management beyond LDL-C reduction

3 Published online November

4 Collaboration with ACC/AHA and the NHLBI Timeline NCEP ATP III Update (2004) NHLBI initiated guideline process (2008) Institute of Medicine Report on Trustworthy Guidelines (2011): Focus specifically on highest quality evidence and Partner with other organizations to develop recommendations Collaboration with ACC/AHA and the NHLBI (June 2013) Charge to ACC/AHA Update clinical practice recommendations for treatment to decrease CVD based on RCTs, systematic reviews and metaanalyses of RCTs. Evaluate higher quality randomized controlled trial (RCT) evidence for cholesterol lowering drug therapy to reduce ASCVD risk RCTs and systematic reviews/metaanalyses of RCTs were independently assessed for quality Less expert opinion than in prior guidelines Use Critical Questions to create the evidence search to develop the guideline Stone,N., 2014 Presentation NLA Scientific Sessions 4

5 On-Treatment LDL-C and CHD Events in Statin Trials 5 Event rate (%) Rx - Statin therapy PRA pravastatin ATV - atorvastatin LIPID - Rx AFCAPS - Rx 4S - Rx CARE - Rx HPS - Rx TNT ATV10 TNT ATV80 PROVE-IT - PRA PROVE-IT ATV Secondary Prevention HPS - Placebo AFCAPS - Placebo CARE - Placebo ASCOT - Placebo LIPID - Placebo WOSCOPS-Placebo WOSCOPS - Rx 4S - Placebo Primary Prevention (1.0) 60 (1.6) 80 (2.1) ASCOT - Rx 100 (2.6) 120 (3.1) 140 (3.6) LDL-C achieved mg/dl 160 (4.1) 180 (4.7) Adapted from Rosensen RS. Exp Opin Emerg Drugs 2004;9(2): LaRosa JC et al. N Engl J Med 2005;352:e-version 200 (5.2)

6 6 3 Critical Questions 1. What is the evidence for LDL-C and Non HDL-C goals for secondary prevention of ASCVD? Reviewed 19 RCTs 2. What is the evidence for LDL-C and Non HDL-C goals for primary prevention of ASCVD? Reviewed 6 RCTs 3. For primary and secondary prevention, what is the impact of lipid levels/effectiveness and safety of specific cholesterol modifying drugs used for lipid management in general and in selected subgroups? The recommendations regarding whom to treat and with what intensity are based on the synthesis of this evidence.

7 7 BENEFITS OF STATINS AND SHORT TERM VASCULAR RISK Cholesterol Treatment Trialists Cochrane Collaboration

8 Predicted 5-year Benefits of LDL-C Reductions with Statins at Different Levels of Risk Major Vascular Events Vascular Deaths 8 1 mmol= mg/dl 2.5 mmol is mg/dl Jackson, R.(2014) Curr Opin Lipid Vol 25,4: Mihaylova, B. et al Lancet 2012; 380:

9 Cochrane Review 18 RCTs 19 Trial arms N=56,394 Statin Benefits 14% i mortality (all cause) 27% i CHD events (fatal and non fatal) 22% i in stroke (fatal and non fatal) 38% i in revascularization Statin Adverse Effects 18% h in diabetes (2.8% on statin vs 2.4% controls) No significant increase in short term risk of Muscle adverse events Liver adverse events Cancer, memory loss Hemorrhagic stroke Taylor F, Huffman et al Cochrane Database Syst Reve 2013

10 Statins Benefit Patients with Increased ASCVD Risk 11 Statin Benefit Groups ASCVD LDL-C above 190 mg/dl Diabetes Type 1 or 2 > 7.5% 10-yr ASCVD Risk Score Select Individuals Also With Increased Risk LDL > 160 or other evidence of genetic dyslipidemia, Family history of ASCVD (first degree male relative < 55, female relative <65) Hs-CRP >2.0 CAC score > 300 Agatston unit or > 75 th percentile for age, sex, and ethnicity ABI < 0.9 Elevated Lifetime Risk of ASCVD

11 12 RISK CALCULATOR Calculate the 10-year ASCVD Risk ACC/AHA guideline recommends Pooled Cohort Assessment Equation Predicts CHD and stroke Non-Hispanic Caucasians and African Americans Women and Men Age

12 13 HIGH INTENSITY STATIN LOWERS LDL BY >50% ATORVASTATIN (40)-80mg ROSUVASTATIN 20 (40) mg

13 14 MODERATE INTENSITY STATIN LOWERS LDL approximately 30-50% ATORVASTATIN 10 (20)mg ROSUVASTATIN (5) 10mg SIMVASTATIN 20-40mg PRAVASTATIN 40-(80)mg LOVASTATIN 40mg FLUVASTATIN 40mg BID PITAVASTATIN 2-4mg

14 15 LOW INTENSITY STATIN LOWERS LESS THAN 30% SIMVASTATIN 10mg PRAVASTATIN 10-20mg LOVASTATIN 20mg FLUVASTATIN 20-40mg PITAVASTATIN 1mg

15 16 HIGH INTENSITY MODERATE OR HIGH INTENSITY MODERATE INTENSITY AGE < 75 with ASCVD AGE with 10 YR RISK SCORE >7.5% AGE with DM with LDL-C mg/dl *LDL >190 mg/dl **AGE >75 with ASCVD DM and 10 YR RISK SC0RE >7.5% *LDL-C > 190 suggests genetic disorder **Age >75 with ASCVD, may continue high intensity statin if tolerated.

16 17 GUIDELINES AND THE REAL WORLD

17 Patients Experiencing Major CHD Events, % Residual Cardiovascular Risk in Major Statin Trials 18 CHD events occur in patients treated with statins Placebo Statin S 1 LIPID 2 CARE 3 HPS 4 WOSCOPS 5 AFCAPS/ TexCAPS 6 N LDL-C -35% -25% -28% -29% -26% -25% Secondary High Risk Primary 1 4S Group. Lancet. 1994;344: LIPID Study Group. N Engl J Med. 1998;339: Sacks FM, et al. N Engl J Med. 1996;335: HPS Collaborative Group. Lancet. 2002;360: Shepherd J, et al. N Engl J Med. 1995;333: Downs JR, et al. JAMA. 1998;279:

18 19 Variability of Achieved LDL-C with High Intensity Statin Boekholdt, SM et al J Am Coll Cardiol. 2014; 64:

19 20 Improve IT Simvastatin 40 mg vs Simva/Ezetimibe in patients stabilized > 10 days post ACS Cannon et al, 2014 AHA Scientific Sessions Presentation, accessed online 2/2/15

20 21 Improve IT Statistically significant reduction in primary endpoint and 3 specified secondary endpoint Largest relative reduction CHD death, MI and urgent coronary revascularization

21 22 Gaps in Evidence Little or No RCT data Triglycerides > 500 LDL-C > 190mg/dL Statin intolerant/phobic Renal failure Multiple co-morbidites For questions regarding complex lipid disorders that are beyond the scope of (this) systematic evidence review, or for which little or no RCT data are available, it is anticipated that clinicians with lipid expertise can contribute to their management

22 NLA Recommendations for Patient-Centered Management of Dyslipidemia Expert panel consensus view Treatment Goals Communicate progress Individual goal based on risk 23 Risk LDL-C Non HDL-C* Low <100 <130 Mod <100 <130 High <100 <130 Very High <70 <100 *Non HDL-C superior to LDL-C

23 24 Non-HDL-C Total Cholesterol HDL = Non-HDL Elevated in patients with increased Cardiometabolic risk Diabetes Metabolic Syndrome Obesity Adiposopathy Labs Results: Elevated Triglycerides Low HDL-C Normal/low LDL-C Small dense LDL Elevated Glucose Abnormal Liver enzymes Elevated markers of inflammation hs-crp Sum of all atherogenic particles

24 25 Triglycerides and CVD Increased Risk PROVE-IT and IDEAL Patients with TGs >150mg/dL were at increased risk even if LDL-C treated to <70mg/dL Genetic: Type I-Lipoprotein Lipase Type IV-Endogenous Secondary causes of hypertriglyceridemia: Diet, Drugs, Diseases/Disorders Treatment Optimize nutrition, weight loss and lifestyle changes For TGs mg/dl, target of therapy is Non HDL-C and LDL-C TGs are not a target for therapy unless >500mg/dL to prevent pancreatitis Medical therapy: statin, fibrates, niacin, prescription strength fish oil Vijay,K. Haffey, T, The Triglyceride Enigma, Lipid Spin. Vol 12, 4

25 26 Low HDL and CV Risk Low HDL-C is a risk factor for CHD, irrespective of LDL-C. Elevated LDL-C and TG greatly increases risk of CHD in patients with low HDL-C. Observational studies suggest that each 1- mg/dl incremental decrease in HDL-C is associated with a 2 3% increase in CHD risk. Ansell BJ. Cleve Clin J Med. 2007;74(10): ,

26 27 Low HDL and CVD Low HDL portends: Increased risk for MI and CAD Mortality (Goldbourt, 2007) Stroke in elderly (Qeverling-Rijnsburger, 2003) Sudden death (Burke, 1999) Re-stenosis after angioplasty (Shah, 1992) Severe, premature atherosclerotic disease in proximal left main (Pearson, 1979) Increased risk for retinopathy in diabetic pts (Sasongko, 2011) For every 1mg/dL drop in HDL-C, risk for DM2 increases 4% (Stern, 2002) Davidson, M.,(2012) HDL Masters class

27 28 HDL HYPOTHESIS Is Raising HDL Beneficial? CETP Inhibitor Trials Niacin Trials Functionality Studies

28 29 Current Recommendations for HDL Treat Non HDL- C & LDL-C to goal Medical therapy with statins SHIFT Trial SARA Trial Diet Avoid trans-fat Low in sugar, refined CHOs Limit saturated fat with good fats Exercise Frequent aerobic exercise >120 min/week Weight Loss Initial decrease HDL-C during active weight loss phase, but will increase after wt plateaus. In Vino Veritas Moderate wine drinking (red or white) protective in those that exercised (Taborsky, 2014) Smoking Cessation Increases HDL-C by 20% Ansel 2003 Circulation Ansel, Toth, (2013)HDL Newsletter Part 2 Kontush, Chapman 2012 HDL Stucture,Metabolism,Function and Therapeutics accessed 1/29/15 Bays et al, NLA Annual Summary of Clinical Lipidology

29 30 Summary Identify individuals at increased risk for ASCVD Treat with proper intensity of statin based on risk Statins are safe and beneficial for both primary and secondary prevention Patients with cardio-metabolic disorders have increased residual risk If LDL-C and Non HDL-C are discordant, the risk follows the Non HDL-C Lifestyle remain cornerstone of lipid management