The New Lipid Guidelines. What you need to know Paul J Kovack, DO, FACOI, FACC. Overview. NHLBI 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
The New Lipid Guidelines What you need to know Paul J Kovack, DO, FACOI, FACC
Overview • NHLBI • 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 • This guideline focuses on treatments to reduce ASCVD events • Not a comprehensive approach to lipid management • Finally, review questions and controversies that have arisen since publication.
Disclosures • I have no disclosures for this talk
Don’t Forget Healthy Lifestyle • Healthy diet • Regular exercise • No tobacco • Maintain healthy weight
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
There are 4 defined Statin Benefit groups • All of these are indicated for statin treatment
1. Patients with clinical ASCVD • Defined by the inclusion criteria for the secondary prevention statin RCT • Coronary artery disease or peripheral artery disease • Acute coronary syndromes • Coronary or other arterial revascularization • Stroke or TIA • PVD presumed to be atherosclerotic
Identifying ASCVD • 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
2. LDL greater than 190 mg/dl • 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
3. Patients with diabetes, age 40-75 years • All have indication for statin • Level of intensity of statin treatment depends on calculated 10 year risk.
4. Age 40-75 years that do not meet above criteria, but have a 10 year risk of >7.5 % • 10 year and lifetime risk as determined by CV Risk Calculator • Specifically designed for this trial • Downloadable on AHA or ACC site • Not without controversy, as the calculator has never before been published or validated
CV Risk Calculator • Risk factors used in calculation • Sex • Age • Race • Total Cholesterol • HDL • Systolic BP • Treated for HBP • Diabetes • Smoker
Data generated with calculator • 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
There are no longer treatment targets for LDL or non-HDL • 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.”
Non-statin therapies • 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?
Recent troublesome non-Statin Trials • 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
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
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
Other factors to 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
What is your patient cannot tolerate statin due to muscle weakness? • 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
High intensity versus low intensity statin therapy • High intensity statin therapy is defined as > 50% reduction of LDL with daily statin • Moderate intensity statin therapy is defined as 30-50% reduction with daily statin • All patients with CAD, regardless of age, should receive high intensity statin therapy if tolerated.
Dose Response of Different Statins Response to Minimum/Maximum Statin Dose Atorvastatin10/80 mg Fluvastatin 20/80 mg Pravastatin 20/80 mg Lovastatin 20/80 mg Simvastatin 20/80 mg % Reduction in LDL-C 31 37 40 47 55 LDL-C = low-density lipoprotein cholesterol Reprinted from Illingworth DR. Med Clin North Am. 2000;84:23–42, with permission from Elsevier Limited.
Comparing statin efficacy 10 mg 20 mg 30 mg 40 mg Atorvastatin Rosuvastatin Simvastatin −28 −37 −46† Mean % Change in LDL-C from Untreated Baseline Value −7 18% with3 titrations −4 14% with3 titrations −6 −7 −5 −6* 9% with2 titrations −3 −3* *P < 0.001 vs. atorvastatin 10 mg and simvastatin 20 mg and 40 mg †P = 0.026 vs. atorvastatin 20 mg LDL–C=low-density lipoprotein cholesterol Jones PH, et al. Am J Cardiol. 2003;92:152–160.
Patients with LDL greater than 190 mg/dl • These patients get high intensity statin treatment • If they cannot tolerate high intensity statin therapy, use Zetia 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
Diabetics aged 40-75 yoa • 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
Nondiabetic patients without known CAD with >7.5% 10 year risk • Statin indicated in these patients • Moderate to high intensity statin therapy recommended
4 Defined Statin Benefit Groups • CAD 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
No longer appropriate strategies • Treat to target • Lower is better • Treat for lifetime risk
No recommendations for these • No indication for starting or discontinuing statins in the following: • NYHA class 2-4 • Or those on dialysis • HIV patients • Solid organ transplant patients • Insufficient data from RCT available
Questions remain • 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
Likely Future Updates to the Cholesterol Guidelines • 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
Controversies • 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 • Guideline panel chairman said they believed that the populations studied by Drs Cook and Ridker were “unusually healthy” and so their MI and stroke rates might be lower than expected.
Calculations may not always make sense • 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.
Where do we go from here? • 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
Summary • 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
“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