updates on the management of dyslipidemia a review of the 2013 acc/aha cholesterol guidelines...

Updates on the Management of Dyslipidemia

A Review of the 2013 ACC/AHA Cholesterol Guidelines

Timothy Gladwell, Pharm.D., BCPS, BCACPAssociate Professor and Vice ChairDepartment of Pharmacy Practice

Husson University School of Pharmacy

Faculty Disclosure

Tim Gladwell, PharmD, BCPS, BCACP does not have any actual or potential conflicts of

interest in relation to this CE activity.

Learning Objectives

• At the conclusion of this session, participants should be able to:– Describe the major differences between the ATP-III and the

2013 ACC/AHA cholesterol guidelines– Discuss the groups of patients for whom statins are

recommended based on the new guidelines, and explain the rationale for the recommendations

– Discuss controversies and unresolved issues surrounding the new lipid guidelines

– Apply an evidence-based approach to the management of patients with dyslipidemia

Patient Case – Mr. Jones• 68-y/o white man - T2DM & HTN• Medications– Aspirin 81mg daily– Metformin 500mg twice daily– Lisinopril 10mg daily

• SH – no tobacco or alcohol; regular exercise & DASH diet

• FH – no premature CAD• BP 134/78mm Hg

Labs:• Chol 168• LDL 92• HDL 37• TG 195• A1c 7.4%

Does Mr. Jones need treatment for dyslipidemia?

Review of ATP-III Guidelines

• National Cholesterol Education Program (NCEP)• Developed by an expert panel for the National Heart,

Lung, and Blood Institute (NHLBI)– First Adult Treatment Panel (ATP-I) released in 1988– ATP-II released in 1993– ATP-III released in 2001– Update to ATP-III released in 2004

Review of ATP-III Guidelines• Treatment assessed through 9-step process– Step 1:Obtain fasting lipid panel– Step 2:Identify CHD or CHD equivalents– Step 3:Determine presence of major risk factors for CHD– Step 4:Assess 10-year risk of CHD using Framingham tables

(if 2+ risk factors and no CHD or CHD equivalents)– Step 5:Determine risk category and LDL goals– Step 6:Initiate TLC if necessary– Step 7:Initiate drug therapy if necessary– Step 8:Identify presence of metabolic syndrome– Step 9:Treat elevated triglycerides or low HDL

ATP III Guidelines At A Glance. Available at https://www.nhlbi.nih.gov/guidelines/cholesterol/atglance.pdf. Accessed 8/25/14

https://www.nhlbi.nih.gov/guidelines/cholesterol/atglance.pdf

Review of ATP-III Guidelines• LDL goals based on risk categories

• Secondary (non-HDL) goals



Patient Case – Mr. Jones• 68-y/o white man - T2DM & HTN• Medications– Aspirin 81mg daily– Metformin 500mg twice daily– Lisinopril 10mg daily




Does Mr. Jones need treatment for dyslipidemia?

Patient Case - Mr. Jones• 68-year-old man with T2DM & HTN– CHD equivalent (T2DM)– Goal LDL<100– Already at goal (statin not necessary)



Patient Case - Mr. Jones• 68-year-old man with T2DM & HTN– Non-HDL level is above goal (131mg/dL)– Reinforce therapeutic lifestyle changes–May consider drug therapy for his ↓HDL/↑TG


BUT – WHAT’S THE EVIDENCE?


Dyslipidemia in DiabetesRepresentative Literature

• Statins for primary prevention– Collaborative Atorvastatin Diabetes Study (CARDS)• T2DM ages 40-75 with > 1 risk factor• Baseline LDL levels averaged ~118mg/dL• Randomized to atorvastatin 10mg or placebo• Stopped early with significant 37% ↓ in CV events• Consistent results regardless of baseline LDL level

– Similar findings in subgroups of other trials• HPS, AFCAPS/TEXCAPS, MEGA

Colhoun HM et al. Lancet 2004;364:685-96.

Dyslipidemia in DiabetesRepresentative Literature

• Agents for HDL/TG modification– ORIGIN trial• T2DM or pre-diabetes aged 50 or older• History of CAD or risk factors for CAD• Approximately ½ of the patients on statins at baseline• At baseline, LDL~112; HDL~46; TG~142• Randomized to 1g omega-3 fatty acids or placebo• No difference in death from CV cause between groups

– Similar findings with other trials• ACCORD (fibrates), AIM-HIGH (niacin)

ORIGIN Trial Investigators. N Engl J Med 2012;367:309-18.

2013 AHA/ACC Cholesterol Guidelines

• Expert panels appointed by NHLBI in 2008– Developed critical questions– Identified highest-quality evidence

• Primarily RCTs and meta-analyses

• Partnered with AHA in 2013 to write recommendations

• Graded according to quality of evidence• Conflict of interest policies enforced• Peer reviewed and endorsed by multiple

organizationsStone NJ et al. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.


• Critical questions addressed by the review–What is the evidence for LDL and non-HDL goals

for the primary and secondary prevention of atherosclerotic cardiovascular disease?

–What is the impact on lipid levels, effectiveness, and safety for specific cholesterol-modifying drugs in the general population and in selected subgroups?

Stone NJ et al. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.


• Summary of key recommendations– Encourage healthy lifestyle– Consider statins for patient groups who have been

shown to benefit in clinical trials– Utilize pooled cohort estimate equation to determine

10-year risk of ASCVD in primary prevention– Assess risk of toxicity in susceptible patients– Initiate statin at appropriate dose based on risk–Monitor for adherence– Little evidence for benefits with non-statin agents



• What about LDL goals?– The panel found no evidence to support the treat-to-

target paradigm• No RCTs have compared different LDL goals

– Potential problems with treat-to-target strategy• Under-treatment if LDL is already at goal• Addition of non-statin drugs to achieve pre-specified

targets may increase risk without reducing ASCVD event rates• Treat-to-target may unnecessarily increase provider visits

and costs


2013 AHA/ACC Cholesterol Guidelines• Four main statin benefit groups

• Age < 75 – High-intensity statin†

• Age > 75 – Moderate-intensity statinASCVD

• High-intensity statinLDL>190

•10-year risk >7.5% - High-intensity statin•10-year risk <7.5% - Moderate-intensity statin

Age 40-75 with diabetes

LDL 70-189

• Moderate- to high-intensity statinAge 40-75 without ASCVD or diabetes10-year risk >7.5%

†Consider moderate-intensity statin if high-intensity is contraindicated, or if safety concerns are an issue



• No specific recommendation made for:– Patients with NYHA Class II-IV heart failure– Patients on maintenance hemodialysis

• In these patients, individualize decision by considering:– Potential reduction in ASCVD risk– Drug-drug interactions– Adverse effects of medication– Patient preference



• Statin intensity†

Agent Low-intensity(↓ LDL <30%)

Moderate-intensity(↓ LDL 30%-

49%)

High-intensity(↓ LDL >50%)

Atorvastatin - 10mg-20mg 40mg-80mg

Rosuvastatin - 5mg-10mg 20mg-40mg

Simvastatin 10mg 20mg-40mg -

Pravastatin 10mg-20mg 40mg-80mg -

Lovastatin 20mg 40mg -

Fluvastatin 20mg-40mg 80mg -

Pitavastatin 1mg 2mg-4mg -†Daily dose required to achieve stated LDL reductions



• Pooled Cohort Risk Assessment Equations– Designed to replace Framingham risk scores– Estimates 10-year and lifetime risk of ASCVD• Includes fatal or nonfatal MI, fatal or nonfatal stroke

– 10-year risk calculator• Input age, sex, race, TC, HDL, SBP, HTN drug use,

diabetes status, and smoking status• Valid for age 40-79 African-American or non-Hispanic

white men and women• Threshold is >7.5%



• Pooled Cohort Risk Assessment Equations– Downloadable spreadsheet and web-based version

available at:

http://my.americanheart.org/cvriskcalculator

http://my.americanheart.org/cvriskcalculator


• Safety issues with statins– Assess for patient characteristics that might pre-

dispose to adverse effects• Impaired renal or hepatic function• History of previous statin intolerance or muscle disorders• Unexplained ALT elevations >3 times the ULN• Concomitant use of interacting drugs• Age > 75

– Consider use of lower-intensity statin if any of these characteristics are present



• Monitoring of statins– Baseline ALT prior to initiation

• Consider baseline CK in patients at risk for muscle disorders• Routine ALT or CK levels not recommended unless

symptomatic

– Baseline fasting lipid panel• Repeat in 4-12 weeks to assess therapeutic response and

every 3-12 months if clinically warranted• Reinforce adherence if response is less than expected• Consider increasing intensity or addition of non-statin if

unable to achieve desired goals• Dose may be decreased if 2 consecutive LDL <40


2013 AHA/ACC Cholesterol Guidelines• Management of adverse effects– Mild to moderate muscle symptoms

• Discontinue statin until muscle symptoms resolve• Once symptoms resolve, re-challenge with a lower dose• If symptoms resume, discontinue statin and re-challenge with

lower dose of different statin once symptoms abate• Gradually titrate to target dose• If symptoms don’t resolve after 2 months, assume it is not statin-

related and resume original statin

– New onset diabetes• Reinforce lifestyle modifications

– Memory impairment• Consider other potential causes before stopping statin



• The role of non-statin agents– Limited evidence to support use of non-statin agents– Consider use of non-statin agents in the following

situations:• In addition to statins in high-risk patients with less than

anticipated response:– Clinical ASCVD and age<75– Baseline LDL>190– Age 40-75 years with diabetes

• As monotherapy in at-risk patients who are completely statin-intolerant• In patients with severe elevations of triglycerides (>500)


Revisiting Mr. Jones• 68-y/o white man - T2DM & HTN• Medications– Aspirin 81mg daily– Metformin 500mg twice daily– Lisinopril 10mg daily




Is he a candidate for a statin based on 2013 AHA guidelines?

Revisiting Mr. Jones• 68-y/o man with T2DM and LDL 92

• Age < 75 – High-intensity statin†

• Age > 75 – Moderate-intensity statinASCVD

• High-intensity statinLDL>190

•10-year risk >7.5% - High-intensity statin•10-year risk <7.5% - Moderate-intensity statin

Age 40-75 with diabetes

LDL 70-189

• Moderate- to high-intensity statinAge 40-75 without ASCVD or diabetes10-year risk >7.5%

†Consider moderate-intensity statin if high-intensity is contraindicated, or if safety concerns are an issue


Revisiting Mr. Jones• 68-year-old man with T2DM & HTN– Current LDL is 92mg/dL– 10-year risk score is 35.9%

– High-intensity statin is recommended


• Clinical controversies– Pooled Cohort CV Risk Calculators• Estimates of 12 million to 45 million additional candidates

for statin therapy based on CV risk estimates– Pencina* et al. estimated 87.4% of men and 53.6% of women ages

60-75 would now be eligible for statins

• Validation attempts have yielded conflicting results:– Ridker† et al. found overestimation of risk by 75%-150% when

applied to data from the Women’s Health Study and the Physician’s Health Study

– Muntner‡ et al. reported good results in actual vs. predicted 5-year risks in a contemporary cohort of the REGARDS study

*Pencina MJ et al. N Engl J Med 2014;370:1422-31.†Ridker PM et al. Lancet 2013;382:1762-5. ‡Muntner P et al. JAMA 2014;311:1406-15.


• Clinical controversies– Removal of LDL goals• Concern over message this sends to patients and providers

– Cholesterol levels are no longer important?

• Role of LDL goals in patient motivation– Do we need a target to support lifestyle changes/adherence

• Does a lack of RCT evidence = lack of benefit?– Decades of clinical experience with “treat-to-target” strategy

• Effect on current performance measures– Will quality assurance measures follow the new guidelines?


• Clinical controversies–Management of other patient groups• Age <40 or >75 years without clinical ASCVD?• 10-year risk of 5%-7.5%?• LDL >160mg/dl or other primary hyperlipidemias?• Additional risk assessment may be necessary

– High sensitivity C-reactive protein– Ankle-brachial index– Coronary artery scores– Family history of premature CHD– Elevated lifetime risk of ASCVD

Summary of Key DifferencesATP-III AHA/ACC

Basis for recommendations Expert opinion based on pathophysiology, observational, & RCT data

Evidence-based recommendations based on RCTs and systematic reviews

Risk stratification CHD equivalents, risk factors, 10-year risk of MI

4 specific risk groups based on benefits in clinical trials

Risk calculation Framingham risk score Pooled cohort equation

Goals of therapy LDL & non-HDL levels(stratified by risk)

Statin intensity (% LDL reduction)

Role for monitoring Fasting lipid panel to assess achievement of goal

Fasting lipid panel to assess adherence/therapeutic response

Role of non-statin agents Encouraged use if needed to achieve LDL or non-HDL goal

Discourages use in most patients because of lack of evidence on improving outcomes


• Applying this information to practice– Remember that these are just guidelines– Apply an evidence-based approach– Consider your patient population– Individualize treatments– Discuss risks and benefits with the patient– Include patient preferences in decision-making

Post-Lecture Question #1Changes in the recommendations of the 2013 AHA/ACC cholesterol guidelines from those in the ATP-III guidelines include:1. Elimination of LDL and non-HDL treatment targets

2. Inclusion of a new Pooled Cohort ASCVD risk estimation calculator

3. A decreased role for non-statin cholesterol lowering agents

4. All of the above

Post-Lecture Question #2Which of the following would be considered a high-intensity statin regimen?

1. Atorvastatin 10 mg daily

2. Rosuvastatin 20mg daily

3. Simvastatin 40mg daily

4. Pravastatin 80mg daily

Post-Lecture Question #3According to the 2013 AHA/ACC cholesterol guidelines, which of the following patients would be most suitable for initiation of a moderate-intensity statin regimen?1. A 65-year-old man with a previous myocardial infarction

2. A 45-year-old woman with Type 2 diabetes and an estimated 10-year risk of ASCVD of 9%

3. An 80-year-old woman with a previous history of ischemic stroke

4. A 24-year-old man with familial hypercholesterolemia and an LDL of 225mg/dL

Questions???

References• National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment

of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Circulation 2002;106:3143-421.

• Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic risk in adults: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.

• Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HAW, Livingstone SJ, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004;364:685-96.

• The ORIGIN Trial Investigators. N-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med 2012;367:309-18.

• Pencina MJ, Navar-Boggan AM, D’Agostino RB Sr, Williams K, Neely B, Sniderman AD, et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med 2014;370:1422-31.

• Ridker PM, Cook NR. Statins: new American guidelines for prevention of cardiovascular disease. Lancet 2013;382:1762-5.

• Muntner P, Colantonio LD, Cushman M, Goff DC Jr, Howard G, Howard VJ, et al. Validation of the atherosclerotic cardiovascular disease pooled cohort risk equations. JAMA 2014;311:1406-15.

updates on the management of dyslipidemia a review of the 2013 acc/aha cholesterol guidelines...

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