2013 ACC/AHA Guidelines on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults 2014 AAHP Fall Seminar Sherry Myatt, PharmD, BCPS Assistant Director of Pharmacy for Clinical Services UAMS Med Center I have no relevant financial interests to disclose for this talk Disclosures NHLBI vs ACC/AHA First new guidelines since ATP III guideline update in 2004 Review the most important statements or changes presented in these guidelines No longer have therapeutic targets New risk calculator Use medications proven to reduce risk, ie statins Avoid medications or supplements that may lower the cholesterol number, but have no data to decrease CV risk Not a comprehensive approach to lipid management Finally, review questions and controversies that have arisen since publication. Overview 1
1. Outline the main differences between the 2013 ACC /AHA cholesterol management guideline and the previous NCEP guideline. Discuss the controversy about the new guideline. 2. Describe the 4 statin benefit groups identified in the 2013 guideline and identify which patients to target for lipid lowering therapy 3. Describe the recommended intensity of statin therapy for each benefit group. List at least 2 regimens of each intensity. 4. Evaluate the recommended initial dose and follow-up of statin therapy. Objectives for Pharmacists 4 63 yo man with STEMI, discharged on a high intensity statin 26 yo woman with elevated LDL C of 220 mg/dl, noted in teens + family history CHD 44 yo woman with diabetes, well-controlled hypertension and micro-albuminuria 56 yo African-American woman with multiple ASCVD risk factors 57 yo white man with LDL-C 165 mg/dl Some Patients to Think About 5 Healthy diet Regular exercise No tobacco Maintain healthy weight Don t Forget Healthy Lifestyle 2
2013 ACC/AHA/NHLBI Guideline on Lifestyle for CVD Prevention Eat a dietary pattern that is rich in fruit, vegetables, whole grains, fish, low-fat dairy, lean poultry, nuts, legumes, and nontropical vegetable oils consistent with a Mediterranean or DASH-type diet. Restrict consumption of saturated fats, trans fats, sweets, sugar-sweetened beverages, and sodium. Engage in aerobic physical activity of moderate to vigorous intensity lasting 40 minutes per session three to four times per week 1. Patients with clinical ASCVD 2. LDL greater than 190 mg/dl 3. Patients with diabetes, age 40-75 years 4. Age 40-75 years that do not meet above criteria, but have a 10 year risk of >7.5 % All of these are indicated for statin treatment 4 Defined Statin Benefit Groups Defined by the inclusion criteria for the secondary prevention statin RCTs: Coronary artery disease or peripheral artery disease Stroke or TIA* Acute coronary syndromes Coronary or other arterial revascularization PVD presumed to be atherosclerotic These patients get High Intensity Statin Therapy 1. Patients with Clinical ASCVD 3
This could be identified in several ways: Heart catheterization Q waves on ECG TEE Coronary CTA Noninvasive testing including, carotid duplex, upper or lower extremity arterial duplex Peripheral angiography Identifying ASCVD This is one of the few times level of cholesterol mentioned in the guidelines These are patients with familial hyperlipidema They deserve special consideration Often start with untreated LDL of 325-400 mg/dl 2. LDL > 190 mg/dl These patients get high intensity statin treatment If they cannot tolerate high intensity statin therapy, use moderate intensity statin +/- or other agent to achieve >50% reduction of baseline LDL. Patients with FH are frequently unable to achieve previous goals even with multiple cholesterol lowering agents In this special case, the authors felt that data has shown significant reductions of ASCVD by decreasing LDL > 50% Can include statin plus another agent LDL > 190 mg/dl 4
LDL levels 70-189 mg/dl and no ASCVD All have indication for statin Level of intensity of statin treatment depends on calculated 10 year risk 3. Diabetics Between 40-75 Years Old Diabetics with > 7.5% 10 year risk get high intensity statin therapy Diabetics with < 7.5% 10 year risk of CAD get moderate intensity statin therapy Statin indicated in all patients with diabetes Diabetics Between 40-75 Years Old 10 year and lifetime risk as determined by new Pooled Cohort Equationss Specifically designed for this trial Downloadable on AHA or ACC site Not without controversy, as the calculator has never before been published or validated 4. Nondiabetic Patients Without Known CAD with >7.5% 10 year risk 5
Risk Factors Used in Calculator Sex Age Race Total Cholesterol HDL Systolic BP Treated for HBP Diabetes Smoker CV Risk Calculator 17 Patient s 10 year risk 10 year risk of someone the same age with optimized risk factors Patient s lifetime risk of ASCVD Lifetime risk of someone with optimal risk factor levels Data Generated With Calculator 6
Statin indicated in these patients **after a risk to benefit discussion with their provider Before initiating statin therapy, clinicians and patients engage in a discussion of the potential for ASCVD risk reduction benefits, potential for adverse effects, drug-drug interactions, and patient preferences Moderate to high intensity statin therapy recommended Nondiabetic Patients Without Known CAD with >7.5% 10 year risk What if you don t fall into one of the 4 categories where statins are indicated? There are no recommendations for treatment in selected individuals who are not in the 4 statin benefit treatment groups In these individuals whose 10 year risk is less that 7.5%, or when the decision is unclear, other factors should be considered: Family history of premature CAD LDL > 160 mg/dl Increased CRP greater than 2.0 Coronary calcium greater than 300 ABI < 0.9 Other Factors to be Considered 7
No indication for starting or discontinuing statins in the following: Patients < 40 or > 75 years of age with no ASCVD or LDL > 190 NYHA class II-IV CHF Or those on dialysis HIV patients Solid organ transplant patients Insufficient data from RCT available No Recommendations for These 23 This is a huge change for patients and providers. No longer treat to target Doesn t fit in well with know your numbers. Goal is no longer lower is better. No More Treatment Targets for LDL or Non-HDL 8
Lack of RCT evidence to support titration of drug therapy to specific LDL C and/or non-hdl C goals Strong evidence that appropriate intensity of statin therapy should be used to reduce ASCVD risk in those most likely to benefit Quantitative comparison of statin benefits with statin risk Nonstatin therapies did not provide ASCVD risk reduction benefits or safety profiles comparable to statin therapy New Perspective on LDL C & Non-HDL C Goals 25 Major difficulties: 1. Current RCT data do not indicate what the target should be 2. Unknown magnitude of additional ASCVD risk reduction with one target compared to another 3. Unknown rate of additional adverse effects from multidrug therapy used to achieve a specific goal 4. Therefore, unknown net benefit from treat-to-target approach Why Not Continue to Treat to Target? 26 For hyperlipidemia, non statin therapies, alone or in combination with statins, do not provide acceptable risk reduction benefits compared to adverse effects. These include: Zetia Fibrates Fish oil Niacin For the most part, these should be avoided with few exceptions Why don t non-statins play a more prominent role in the new guidelines? Non-Statin Therapies 9
Fibrate ACCORD. N Engl J Med 2010; 362:1563-1574 FIELD. Lancet; 366:1849-1861 Fish oil Risk and Prevention Study Group. N Eng J Med 2013; 368:1800-1808 Omega-3 Fatty Acid Supplementation and Risk of Cardiovascular Events. JAMA 2012; 308(10):1024-1033 SELECT. JNCI 2013; July 10 Recent Troublesome Non-Statin Trials Niacin HPS2-THRIVE (Treatment of HDL to reduce the Incidence of Vascular Events.) European Heart Journal 2013; 34:1279-1291 AIM-HIGH N Eng J Med 2011; 365:2255-2267 Zetia ENHANCE. N Eng J Med 2008; 358:1431-1443 ARBITER 6-HALTS. N Eng J Med 2009; 361:2113-2122 SEAS. N Eng J Med; 359:1343-1356 IMPROVE-IT ongoing Recent Troublesome Non-Statin Trials Use the maximum tolerated intensity of statin Consider addition of a nonstatin cholesterol-lowering drug(s) If a less-than-anticipated therapeutic response persists Only if ASCVD risk-reduction benefits outweigh the potential for adverse effects in higher-risk persons: Clinical ASCVD <75 years of age Baseline LDL-C 190 mg/dl Diabetes mellitus 40 to 75 years of age Nonstatin cholesterol-lowering drugs shown to reduce ASCVD events in RCTs are preferred Non-Statin Therapy Considerations 30 10
Readdress lifestyle issues Decrease the dose of statin Try another statin Check vitamin D levels and replace Evaluate for other conditions that may cause muscle weakness What if your patient cannot tolerate statin due to muscle weakness? If unexplained severe muscle symptoms or fatigue develop during statin therapy: Promptly discontinue the statin Address possibility of rhabdomyolysis with: CK Creatinine urine analysis for myoglobinuria What if your patient cannot tolerate statin due to muscle weakness? 32 CAD, CVD or PAD LDL >190 mg/dl Diabetics, age 40-75 years with LDL 70-189 mg/dl Age 40-75 years that don t meet above criteria, but have a calculated 10 year risk of > 7.5% of developing CAD 4 Defined Statin Benefit Groups 11
Treat to target Lower is better Treat for lifetime risk No Longer Appropriate Strategies Add in data for groups where RCT become more available Treatment of hypertriglyceremia Use of non-hdl in decision making Whether on-treatment markers such as Apo B, Lp(a), or LDL particles are useful to guide treament Best approaches to using noninvasive imaging for refining risk estimates Questions Remain How lifetime risk should be used and the optimal age to begin statin therapy to reduce lifetime risk of ASCVD Subgroups of individuals with heart failure or undergoing dialysis that might benefit from statin therapy Long-term effects of statin-associated new onset diabetes and management Efficacy and safety of statins in patients excluded from RCT to date (eg, HIV positive or solid organ transplant) Role of pharmacogenetic testing Likely Future Updates 12
Calculator may overestimate risk and lead to inappropriate use of statins, specifically in primary prevention. During the review phase of the guidelines, Dr. Ridker and Cook pointed out that the calculator was not working among the populations it was tested on by the guideline authors. Concern that the calculator over predicted risk by 75 150% So patients from a previously studied population might have had an actual risk of 4% but the calculator might have calculated a risk of 8%, warranting statin therapy. Controversies Dr. Nissen cites examples 47 year old African-American with TChol 160, HDL 44, SBP 130 on 25 mg HCTZ, nondiabetic, nonsmoker has 10 year risk of 7.6% 60 year old African-American with no risk factors, TChol 150, SBP 125 on no meds, nondiabetic, nonsmoker has 10 year risk of 7.5% Similar for a healthy white man aged 58 44 year old nonsmoking, nondiabetic white man with strong family history of MI, total cholesterol of 250 mg/dl, LDL 182, HDL 28, SBP 120 on no meds has 5% calculated risk. Calculations may not always make sense Suspend guidelines? Evaluate risk calculator accuracy using current populations and make adjustments. Continue guideline and review new evidence as it becomes available Continue the discussion Where do we go from here? 13
1. 63 yo man with STEMI, discharged on a high intensity statin 2. 26 yo woman with elevated LDL C of 220 mg/dl, noted in teens + family history CHD 3. 44 yo woman with diabetes, well-controlled hypertension and micro-albuminuria 4. 56 yo African-American woman with multiple ASCVD risk factors 5. 57 yo white man with LDL-C 165 mg/dl Remember Our Patients? 40 ASCVD risk calculation NOT needed: Case 1: ASCVD High-intensity statin therapy for optimal risk reduction in those <75 years who tolerate it Moderate intensity may be initiated or continued if >75 yo or if high-intensity Rx not safe or not tolerated Case 2: LDL C 190 mg/dl (secondary causes ruled out) Evidence supports high-intensity statin therapy LDL C levels may still remain very high, even after the intensity of statin therapy has been achieved; addition of a nonstatin drug may be considered to further lower LDL C Remember Our Patients? 41 42 14
ASCVD risk calculator useful: Case 3: Diabetes; 40-75 yo; LDL C 70-189 mg/dl Moderate-intensity statin to be initiated or continued High-intensity statin reasonable if estimated 10-year ASCVD risk calculated to be >7.5% Cases 4 & 5: Primary prevention; 40-75 yo; LDL C 70-189 mg/dl Use Pooled Cohort Equations (risk calculator) to estimate 10-year ASCVD risk for African American and white individuals to guide initiation of statin therapy Clinician-patient discussion before treatment is initiated Moderate or high intensity statin when >7.5% 10-year ASCVD risk Moderate intensity statin therapy reasonable when >5% 10-year ASCVD risk or when other characteristics that increase ASCVD risk are present Remember Our Patients? 43 44 No longer use targets for cholesterol levels Identify patients at risk Know the 4 high risk groups Use medications proven to reduce risk, ie statins Encourage healthy lifestyle Understand that questions and concerns remain Summary 15
Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning Winston Churchill, 1942 Which of the following is not one of the risk factors considered in the10year CV risk calculator? 1. Smoking 2. Gender 3. Age 4. CAD Which of the following statins would be considered high intensity? 1. Lovastatin 80mg/d 2. Atorvastatin 80mg/d 3. Rosuvastatin 10mg/d 4. Simvastatin 40mg/d Quiz 47 Which recommendation is found in the new guidelines? 1. An LDL goal of < 100 mg/dl is recommended for patients with CV disease. 2. Patients aged 40-75 with DM should get a statin. 3. Most pts over age 75 should get a high intensity statin. 4. Niacin should be started if HDL is < 40 mg/dl. Which patient requires a risk assessment using the Pooled Cohort Analysis? 1. A 30 year old white male with LDL-c 205 2. A 70 year old woman with a recent CVA 3. A 50 year old black man with HTN 4. A 45 white woman with DM and PVD Quiz 48 16