What do the guidelines say about combination therapy? Christie M. Ballantyne, MD Center for Cardiovascular Disease Prevention Methodist DeBakey Heart & Vascular Center Baylor College of Medicine Houston, Texas
Statin Benefit Groups Secondary Prevention Diabetes 40 to 75 yrs LDL-C 70-189 mg/dl LDL-C 190 mg/dl Rx: Optimal benefit with high intensity statins lower LDL-C 50% Use moderate intensity if age >75 or can t tolerate high intensity Primary Prevention 40 to 75 yrs LDL-C 70-189 mg/dl ASCVD Risk 7.5 % Rx: Moderate intensity or high intensity statin Statin Rx not automatic, requires clinician-patient discussion
2013 ACC/AHA Cholesterol Guidelines: Statin Therapy Intensity High ( 50% LDL-C ) Atorvastatin 40 80 mg Rosuvastatin 20 40 mg Moderate (30 <50% LDL-C ) Atorvastatin 10 20 mg Fluvastatin 40 mg bid Fluvastatin XL 80 mg Lovastatin 40 mg Pitavastatin 2 4 mg Pravastatin 40 80 mg Rosuvastatin 5 10 mg Simvastatin 20 40 mg Low (<30% LDL-C ) Fluvastatin 20 40 mg Lovastatin 20 mg Pitavastatin 1 mg Pravastatin 10 20 mg Simvastatin 10 mg Stone NJ et al. J Am Coll Cardiol 2014;63:2889 2934.
What Are Some Common Themes Across These Guidelines Aggressive Treatment of patients with established atherosclerotic cardiovascular disease (ASCVD) Statins as the first line therapy for these high-risk patients Moderate to high intensity statin therapy Guideline ACC/AHA 2013 guidelines National Lipid Association Recommendations (2014) Canadian Cardiovascular Society Guidelines (2012) ESC/EAS Guidelines 2011 Recommendation I/A -- Strong recommendation, Moderate Quality Evidence I / A IIa / A (if LDL-C <100 mg/dl) 1. J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2889-934 2. J Clin Lipidol. 2014 Sep-Oct;8(5):473-88. 3. Can J Cardiol. 2013 Feb;29(2):151-67 4. Eur Heart J. 2011 Jul;32(14):1769-818.
Current Lipid Management Guidelines Recommend Evidence-Based Statin Therapy for Managing CV Risk in High-Risk Populations Secondary prevention ACC/AHA 1 NICE 2 ESC 3 75 yr: high-intensity statin * Start atorvastatin 80 mg or equivalent LDL-C <1.8 mmol/l (<~70 mg/dl) >75 yr: moderate statin or LDL-C 50% LDL-C 190 mg/dl High-intensity statin * 10-yr risk 10%: offer atorvastatin 20 mg LDL-C <2.5 mmol/l (<~100 mg/dl) Diabetes 10-yr risk 7.5%: high-intensity statin * 10-yr risk <7.5%: moderateintensity statin Type 1: offer atorvastatin 20 mg Type 2 + 10-yr risk 10%: offer atorvastatin 20 mg ASCVD or additional risk factors: LDL-C <1.8 mmol/l or LDL-C 50% No ASCVD: LDL-C <2.5 mmol/l Primary prevention 10-yr risk 7.5%: moderate - to high * -intensity statin 10-yr risk 10%: offer atorvastatin 20 mg Age 85: consider atorvastatin 20 mg LDL-C <1.8 to <3.0 mmol/l (<~70 to 115 mg/dl) according to SCORE risk First-line drug Highest tolerated statin Atorvastatin or equivalent Highest tolerated statin Combination with non-statin If target not reached with highest tolerated statin Do not offer fibrate, niacin, bile acid sequestrant or omega-3 fatty acid Non-statin If statin not tolerated Do not offer fibrate, niacin, bile acid sequestrant or omega-3 fatty acid If target not reached with highest tolerated statin Fibrates, niacin: mainly to triglyceride and HDL-C. Ezetimibe alone not recommended 1. Stone NJ, et al. J Am Coll Cardiol. 2014;63:2889 2934. 2. National Institute for Health and Care Excellence Lipid modification July 2014 http://www.nice.org.uk/guidance/cg181 3. Fifth Joint Task Force on CVD Prevention in Clinical Practice. Eur Heart J. 2012;33:1635 1701. *Expected to reduce LDL-C by 50% Expected to reduce LDL-C by 30 to <50%
2013 ACC/AHA Guideline Statement Section 4.4 ".maximal statin therapy might not be adequate to lower LDL-C sufficiently to reduce ASCVD risk in individuals with primary severe elevations in LDL-C. In addition to a maximally tolerated dose of statin, nonstatin cholesterol-lowering medications are often needed to lower LDL-C to acceptable levels in these individuals." 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. Circulation 2014;129:S14 J Am Coll Cardiol 2014;63:2905
2013 ACC/AHA Cholesterol Guideline Recommendations: Statin Therapy: Monitoring Therapeutic Response and Adherence Stone NJ et al. J Am Coll Cardiol 2014;63:2889 2934.
2013 ACC/AHA Guideline Statement Section 6.3.2 "Clinicians treating high-risk patients who have a less-than-anticipated response to statins, who are unable to tolerate a less-thanrecommended intensity of a statin, or who are completely statin intolerant, may consider the addition of a nonstatin cholesterol-lowering therapy." 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. Circulation 2014;129:S23 J Am Coll Cardiol 2014;63:2913
2013 ACC/AHA Cholesterol Guidelines: Insufficient Response to Statin Therapy (II) Addition of nonstatin cholesterol-lowering drug(s), preferably with ASCVD event reduction shown in RCTs, may be considered if ASCVD riskreduction benefits outweigh potential for adverse effects in individuals at higher ASCVD risk receiving maximum-tolerated intensity of statin therapy: [IIb/C] Clinical ASCVD* and age <75 years Baseline LDL-C 190 mg/dl Diabetes and age 40 75 years In individuals who are candidates for statin treatment but are completely statin intolerant, it is reasonable to use nonstatin cholesterol-lowering drugs that have been shown to reduce ASCVD events in RCTs if the ASCVD riskreduction benefits outweigh the potential for adverse effects [IIa/B] *Acute coronary syndromes, history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin Stone NJ et al. J Am Coll Cardiol 2014;63:2889 2934.
Despite Statin Therapy, Many High-Risk Patients Have Marked LDL Elevations Gitt AK, et al. Eur J Prev Cardiol. 2012;19:221 30. Graph adapted from: Gitt AK, et al. Eur J Prev Cardiol. 2012.
2013 ACC/AHA Guideline Statement Intensity of treatment is dependent upon the absolute risk. Although there are no longer specific LDL-C levels or goals as in prior guidelines, LDL-c levels are considered in 3 of the 4 categories as levels to guide the decision process for the initiation of therapy and LDL-C levels are measured in assessing the response of therapy
2013 ACC/AHA Guideline Statement Although the ACC guidelines clearly describe a role for non statin therapies, the interpretation of the language may be unclear to both health care practitioners However the conceptual framework of the guidelines which consider absolute risk and LDL-C levels for initiation of therapy, these same variables can be applied to the decision process of when to initiate non statin therapy