Pharmacology Update: New Recommendations for the Management of Hypertension and High Blood Cholesterol

Transcription

1 Pharmacology Update: New Recommendations for the Management of Hypertension and High Blood Cholesterol January 29, 2014 and February 26, 2014 Joseph Saseen, Pharm.D., FASHP, FCCP, BCPS Professor and Vice Chair, Department of Clinical Pharmacy University of Colorado Anschutz Medical Campus

2 Disclosure Joseph J. Saseen Reports no relevant financial relationships

3 Patient Cases 50-year-old African American man has hypertension. His a smoker. Despite lifestyle modifications for 6 months, BP is 156/96 mm Hg. TC = 205 mg/dl, HDL-C = 40 mg/dl, LDL-C = 120 mg/dl, triglycerides = 225. No chronic medications. 70-year-old woman with hypertension, CHD (s/p MI), dyslipidemia. Adherent with atorvastatin 20 mg daily, carvedilol 25 mg twice daily and lisinopril 40 mg daily. BP is 144/90 mm Hg. No fasting lipid panel available. 60-year-old white man with hypertension and type 2 diabetes. Adherent with amlodipine 10 mg daily, HCTZ 25 mg daily, and ezetimibe/simvastatin 10/10 mg daily. BP is 128/78 mm Hg, LDL-C is 65 mg/dl. How should these patients be treated?

4 Learning Objectives Understand the process for developing new hypertension, high blood cholesterol, and assessment of cardiovascular risk guidelines Review recommendations from clinical guidelines, consensus statement and other position papers that have been published over the past few years that relate to the treatment of hypertension and dyslipidemia Describe the evidence supporting new guideline recommendations for the management of hypertension and high blood cholesterol. List patient specific blood pressure goals for patients with hypertension Debate which antihypertensive agents are most appropriate to use considering patient specific factors. Identify patients who are eligible for statin-based therapy and how they should be treated Describe the role of combination lipid-lowering therapy Manage patients who present with statin-associated muscle related side effects

5 American Heart Association (AHA) Heart Disease and Stroke Statistics 2014 Update 83.6 Million patients in the U.S. have Cardiovascular Disease Millions of Patients TC=total cholesterol; LDL-C = low-density lipoprotein cholesterol; CHD=coronary heart disease; PAD = peripheral artery disease

6 0.95 Lipoprotein Subclasses VLDL Chylomicrons IDL Density (g/ml) LDL LDL Cholesterol Chylomicron Remnants Triglycerides HDL HDL 2 HDL Cholesterol Non-HDL Cholesterol Apo B Diameter (nm)

7 2004: NCEP ATP III Goals Risk Category LDL-C Goal Non-HDL-C Goal Initiate TLC Consider Drug Treatment (mg/dl) (mg/dl) (mg/dl) (mg/dl) High Risk: CHD or CHD Equivalent (10-y risk > 20%) <100 Optional Goal: <70* <130 < <100: for high risk patients Moderately High Risk: 2+ Risk Factors (10-y risk 10-20%) <130 Optional Goal: <100 < : consider to achieve LDL-C goal of <100 Moderate Risk: 2+ Risk Factors (10-y risk < 10%) <130 < Lower Risk: 0-1 Risk Factors (10-y risk < 10%) <160 < : LDL-C Lowering Drugs Optional * For Very High Risk patients NCEP ATP III =National Cholesterol Education Program. Adult Treatment Panel III guidelines. TLC= Therapeutic Lifestyle changes Grundy S, et al. Circulation. 2004;110:

8 National Heart Lung and Blood Institute: Systematic Evidence Reviews in Development Director's Corner Message: NHLBI adopts new collaborative partnership model for clinical practice guidelines development Blood Pressure Draft Finished Federal Review Expert Review Advisory Council HHS Clearance Partnerships Formed Completed Completed Completed Completed Pending Ongoing Partner Release Cholesterol Completed Completed Completed Completed Pending Ongoing ACC/AHA Obesity Completed Completed Completed Completed Pending Ongoing ACC/AHA Lifestyle Completed Completed Completed Completed Pending Ongoing ACC/AHA Risk Assessment Completed Completed Completed Completed Pending Ongoing ACC/AHA Last Updated November

9 Clinical Practice Guidelines for Prevention (November 12, 2013)

10 2013 ACC/AHA Guidelines Focus Three Critical Questions 1. What is the evidence for LDL-C and non-hdl-c goals for the secondary prevention of ASCVD? 2. What is the evidence for LDL-C and non-hdl-c goals for the primary prevention of ASCVD? 3. For primary and secondary prevention, what is the impact on lipid levels, effectiveness, and safety of specific cholesterol-modifying drugs used for lipid management in general and in selected subgroups? Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

11 2013 ACC/AHA Guidelines Preamble Guidelines attempt to define practices that meet the needs of patients in most circumstances and are not a replacement for clinical judgment. The ultimate decision about care of a particular patient must be made by the healthcare provider and patient in light of the circumstances presented by that patient. As a result, situations might arise in which deviations from these guidelines may be appropriate. Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

12 Evidence-Based Recommendations From randomized controlled trials (RCTs), meta-analyses, and observational studies mapped to ACC/AHA format: Class of Recommendations Class I: Benefits >>> Risk Class IIa: Benefits >> Risk Class IIb: Benefit Risk Level of Evidence Level A: Multiple populations; data from multiple RCTs or meta-analyses Level B: Limited populations and single RCT or noncontrolled studies Level C: Very limited populations; consensus opinion Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

13 What is new in the 2013 ACC/AHA Blood Cholesterol Guideline? The panel makes no recommendations for or against specific LDL-C or non-hdl-c targets for primary or secondary prevention of ASCVD Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

14 What is new in the 2013 ACC/AHA Blood Cholesterol Guideline? Focus on Atherosclerotic Cardiovascular Disease (ASCVD) reduction 4 Statin Benefit Groups New global risk assessment calculator for primary prevention patients Safety recommendations Role of biomarkers and noninvasive tests Planned further updates to cholesterol guideline Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

15 ASCVD Statin Benefit Groups Heart healthy lifestyle habits are the foundation of ASCVD prevention. In individuals not receiving cholesterol-lowering drug therapy, recalculate estimated 10-y ASCVD risk every 4-6 y in individuals aged y without clinical ASCVD or diabetes and with LDL C mg/dl. Adults age >21 y and a candidate for statin therapy Yes Clinical ASCVD No Yes Yes Age <75 y High-intensity statin (Moderate-intensity statin if not candidate for high-intensity statin) Age >75 y OR if not candidate for high-intensity statin Moderate-intensity statin Definitions of High- and Moderate-Intensity Statin Therapy High Daily dose lowers LDL-C by approx. 50% Moderate Daily dose lowers LDL-C by approx. 20% to <50% LDL-C 190 mg/dl No Diabetes Type 1 or 2 Age y No Yes Yes High-intensity statin (Moderate-intensity statin if not candidate for high-intensity statin) Moderate-intensity statin Estimated 10-y ASCVD risk 7.5%* High-intensity statin Estimate 10-y ASCVD Risk with Pooled Cohort Equations* 7.5% estimated 10-y ASCVD risk and age y Yes Moderate-to-High Intensity Statin No ASCVD prevention benefit of statin therapy may be less clear in other groups In selected individuals, consider additional factors influencing ASCVD risk and potential ASCVD risk benefits and adverse effects, drug-drug interactions, and patient preferences for statin treatment Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

16 4 Statin Benefit Groups Clinical ASCVD LDL-C 190 mg/dl Diabetes Type 1 or 2 Age y 7.5% estimated 10-y ASCVD risk and age y Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

17 Clinical Atherosclerotic Cardiovascular Disease (ASCVD) Coronary heart disease (CHD) Acute Coronary Syndromes History of myocardial infarction Stable or unstable angina Coronary revascularization Symptomatic carotid artery disease Stroke TIA presumed to be of atherosclerotic origin Peripheral arterial disease or revascularization Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

18 ACC/AHA 2013 Blood Cholesterol Guideline: ASCVD Class I Recommendations High-Intensity statin therapy should be initiated or continued as first line therapy in men and women for < 75 years of age who have clinical ASCVD, unless contraindicated In individuals with clinical ASCVD in whom high- Intensity statin therapy would otherwise be used, when high-intensity statin therapy is contraindicated or when characteristics predisposing to statin-associated adverse effects are present, moderate-intensity statin should be used as the second option if tolerated Level of Evidence A A Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

19 ACC/AHA 2013 Blood Cholesterol Guideline: ASCVD Class IIa Recommendation In individuals with clinical ASCVD > 75 years of age, it is reasonable to evaluate the potential for ASCVD riskreduction benefit and for adverse effects, DDIs, and to consider patient preferences, when initiating a moderate to high-intensity statin. It is reasonable to continue statin therapy in those who are tolerating it Level of Evidence B Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

20 Heart Protection Study (HPS) Double-blind, randomized, placebo-controlled trial 22,536 patients, age years, at increased risk of CHD death due to prior disease: MI or other CHD Occlusive disease of non-coronary arteries, or Diabetes mellitus or treated hypertension Total cholesterol >3.5 mmol/l (>135 mg/dl) Randomized to simvastatin 40 mg daily or placebo Statins not considered clearly indicated or contraindicated by patient s own doctors Primary Endpoint: Major vascular events Heart Protection Study Collaborative Group. Lancet. 2002;360:7-22.

21 HPS: Primary Endpoint Results by Group SIMVASTATIN PLACEBO (10,269) (10,267) Rate ratio & 95% CI STATIN better PLACEBO better Previous MI Other CHD (not MI) No prior CHD CVD PVD Diabetes ALL PATIENTS 999 (23.5%) 1250 (29.4%) 460 (18.9%) 591 (24.2%) 172 (18.7%) 212 (23.6%) 327 (24.7%) 420 (30.5%) 276 (13.8%) 367 (18.6%) 2033 (19.8%) 2585 (25.2%) 24% Relative Risk Reduction (P< ) Heart Protection Study Collaborative Group. Lancet. 2002;360:7-22.

22 LaRosa JC, et al. N Engl J Med. 2005;352: Treating to New Targets (TNT): Study Design 10,001 patients with clinically evident CHD and LDL-C <130 mg/dl while taking atorvastatin 10 mg daily Double-blind, placebo-controlled trial over 5 years Patients randomized to atorvastatin 80 mg or 10 mg Primary end point: Time to first major CV event (CHD death, nonprocedural myocardial infarction, resuscitation after cardiac arrest, or stroke)

23 LaRosa JC, et al. N Engl J Med. 2005;352: Treating to New Targets (TNT): LDL-C Results and Primary Endpoint P<0.001 Atorvastatin 10 mg Atorvastatin 80 mg 22% Relative Risk Reduction P< Mean LDL-C Value (mg/dl) 0 Patients with Major CV Event (%)

24 ACC/AHA 2013 Blood Cholesterol Guideline: Statin Intensity High-Intensity Moderate-Intensity Low-Intensity Daily dose lowers LDL C on average, by ~ 50% Atorvastatin (40) 80 mg Rosuvastatin 20 (40) mg Daily dose lowers LDL C on average, by ~ 30 to <50% Atorvastatin 10 (20) mg Rosuvastatin (5) 10 mg Simvastatin mg Pravastatin 40 (80) mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg bid Pitavastatin 2 4 mg Daily dose lowers LDL C on average, by <30% Simvastatin 10 mg Pravastatin mg Lovastatin 20 mg Fluvastatin mg Pitavastatin 1 mg Specific statins and doses are noted in bold that were evaluated in randomized controlled trials. Statins and doses that are approved by the U.S. FDA but were not tested in the RCTs reviewed are listed in italics. Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

25 Statin Therapy in Clinical ASCVD Clinical ASCVD Not currently on statin therapy Initial evaluation prior to statin initiation Fasting lipid panel* ALT CK (if indicated) Consider evaluation for other secondary causes or conditions that may influence statin safety Evaluate and Treat Laboratory Abnormalities 1. Triglycerides 500 mg/dl 2. LDL C 190 mg/dl Secondary causes If primary, screen family for FH 3. Unexplained ALT >3X ULN Aged <75 y without contraindications, conditions or drug-drug interactions influencing statin safety, or a history of statin intolerance Aged >75 y OR with conditions or drug-drug interactions influencing statin safety, or a history of statin intolerance Initiate high-intensity statin therapy Counsel on healthy lifestyle habits Initiate moderate-intensity statin therapy Counsel on healthy lifestyle habits Monitor statin therapy Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

26 Secondary Causes Most Commonly Encountered Secondary Cause Elevated LDL C Elevated Triglycerides Diet Drugs Diseases Disorders and altered states of metabolism Saturated or trans fats, weight gain, anorexia Diuretics, cyclosporine, glucocorticoids, amiodarone Biliary obstruction, nephrotic syndrome Hypothyroidism, obesity, pregnancy Weight gain, very low-fat diets, high intake of refined carbohydrates, excessive alcohol intake Oral estrogens, glucocorticoids, bile acid sequestrants, protease inhibitors, retinoic acid, anabolic steroids, sirolimus, raloxifene, tamoxifen, beta blockers (not carvedilol), thiazides Nephrotic syndrome, chronic renal failure, lipodystrophies Diabetes (poorly controlled), hypothyroidism, obesity; pregnancy Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

27 4 Statin Benefit Groups Clinical ASCVD LDL-C 190 mg/dl Diabetes Type 1 or 2 Age y 7.5% estimated 10-y ASCVD risk and age y Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

28 ACC/AHA 2013 Blood Cholesterol Guideline: LDL-C 190 mg/dl Class I Recommendations Adults 21 years of age with primary LDL C 190 mg/dl should be treated with statin therapy (10-year ASCVD risk estimation is not required): Use high-intensity statin therapy unless contraindicated. For individuals unable to tolerate high-intensity statin therapy, use the maximum tolerated statin intensity Level of Evidence B Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

29 ACC/AHA 2013 Blood Cholesterol Guideline: LDL-C 190 mg/dl Class IIa Recommendation For individuals 21 years of age with an untreated primary LDL C 190 mg/dl, it is reasonable to intensify statin therapy to achieve at least a 50% LDL C reduction. Class IIb Recommendation For individuals 21 years of age with an untreated primary LDL C 190 mg/dl, after the maximum intensity of statin therapy has been achieved, addition of a nonstatin drug may be considered to further lower LDL C. Evaluate the potential for ASCVD risk reduction benefits, adverse effects, drug-drug interactions, and consider patient preferences. Level of Evidence B Level of Evidence C Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

30 National Lipid Association: Familial Hypercholesterolemia Familial hypercholesterolemias (FH) are genetic defects resulting in severe cholesterol elevations and increased risk of premature CHD Prevalence of FH is 1 in 300 to 500 Homozygous FH affects 1 in 1,000,000 Aggressive lipid lowering is necessary Target LDL-C reduction of at least 50% Greater LDL-C reductions may be necessary for FH patients with other CHD risk factors Journal of Clinical Lipidology 2011;5:

31 Lomitapide (Juxtapid) Approved December 24, 2012 Microsomal triglyceride transfer protein inhibitor that decreases lipoprotein production Indication: Adjunct to diet and other lipid-lowering treatments to reduce LDL-C, TC, apo B, non-hdl-c in homozygous FH Dosing: 5 mg daily titrated to a max of 60 mg daily Adverse effects: hepatic steatosis, elevated hepatic transaminases; GI adverse reactions (93%) could decreased absorption of vitamin E, alpha linoleic acid, linoleic acid, EPA, DHA (supplement recommended) Only available through a restricted Risk Evaluation and Mitigation Strategy (REMS) program

32 Mipomersen sodium (Kynamro) Approved January 30, 2013 Antisense oligonucleotide that decreases secretion of apo B containing lipoproteins from the liver Indication: Adjunct to lipid-lowering medications and diet to reduce LDL-C, apo B, TC, non-hdl-c in patients with homozygous FH Dosing: 200 mg once weekly subcutaneous injection Adverse effects: injection site reactions (84%), flulike symptoms (30%), elevated hepatic transaminases Only available through a restricted Risk Evaluation and Mitigation Strategy (REMS) program

33 Mean Additional Lipid-Lowering with Lomitapide Standard HoFH Therapy Mipomersen LDL-C 40% TC 36% apob 39% nonhdl-c 40% TG 45% HDL-C 7% LDL-C 21% TC 24% apob 19% nonhdl-c 22% TG 18% HDL-C 11% Juxtapid Product Insert, Aegerion Pharmaceuticals, Inc. Cambridge, MA. December Kynamro Product Insert, Genzyme Corporation. Cambridge, MA. January 2013.

34 4 Statin Benefit Groups Clinical ASCVD LDL-C 190 mg/dl Diabetes Type 1 or 2 Age y 7.5% estimated 10-y ASCVD risk and age y Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

35 ACC/AHA 2013 Blood Cholesterol Guideline: Primary Prevention in DM and LDL-C mg/dl Class I Recommendation Moderate-Intensity statin therapy should be initiated or continued for adults 40 to 75 years of age with DM Class IIa Recommendation High-Intensity statin therapy is reasonable for adults age 40 to 75 years of age with DM with a 10 year ASCVD risk > 7.5% unless contraindicated In adults with DM less than 40 or > 75 years of age it is reasonable to evaluate for the potential ASCVD benefits and for adverse effects, DDIs, and to consider patient preference when deciding to initiate, continue, or intensify statin therapy Level of Evidence A Level of Evidence B C Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

36 Collaborative AtoRvastatin Diabetes Study (CARDS) 2838 primary prevention patients with type 2 diabetes No prior MI, CHD, CVA or severe peripheral arterial disease At least 1 other CV risk factor such as smoking, hypertension, retinopathy, or microalbuminuria LDL-C levels 160 mg/dl and TG levels 600 mg/dl Randomized to placebo or atorvastatin 10 mg daily Primary endpoint: Time to first major CV event (CHD death, nonfatal MI, revascularization, stroke) Trial stopped at a median of 3.9 years, 2 years early Colhoun HM, et al. Lancet. 2004;364:

37 CARDS: Primary End Point Results Mean baseline LDL-C 117 mg/dl reduced 40% with atorvastatin (P<0<0001) Cumulative Hazard (%) Placebo 127 Events Atorvastatin 10 mg 83 events Years 36% Relative Risk Reduction P=0.001 Colhoun HM, et al. Lancet. 2004;364:

38 Diabetes Care 2006;29: ) Treat to New Targets (TNT) study: Subgroup analysis of 1501 patients with diabetes 25 Major CV event (%) mg atorvastatin Mean LDL = 99 mg/dl 80 mg atorvastatin Mean LDL = 77 mg/dl 25% RR reduction p= Time (years)

39 ACC/AHA Guideline on the Assessment of Cardiovascular Risk Based on the Pooled Cohort Equations Predicts 10-year risk (and lifetime risk) of: Nonfatal/Fatal Myocardial Infarction Nonfatal/Fatal Stroke Information required: Age, sex, race, total cholesterol, HDL-C, systolic blood pressure, blood pressure lowering medication use, diabetes status, smoking status

40 48-year-old African American woman with type 2 diabetes. Non-smoker. BP is 136/86 mm Hg on antihypertensive drug therapy. TC = 200 mg/dl, HDL-C = 45 mg/dl, not on a statin Year and Lifetime ASCVD Risks Predicted Risk (%) Your 10-Year ASCVD Risk (%) 10-Year ASCVD Risk (%) for Someone Your Age with Optimal Risk Factor Levels (shown above in column E) Your Lifetime ASCVD Risk* (%) Lifetime ASCVD Risk (%) for Someone at Age 50 with Optimal Risk Factor Levels (shown above in column E)

41 4 Statin Benefit Groups Clinical ASCVD LDL-C 190 mg/dl Diabetes Type 1 or 2 Age y 7.5% estimated 10-y ASCVD risk and age y Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

42 ACC/AHA 2013 Blood Cholesterol Guideline: Primary Prevention no DM and LDL-C mg/dl Class I Recommendations The pooled cohort equations should be used to estimate 10 year ASCVD risk for individuals with and LDL-C between 70 to 189 mg/dl without clinical ASCVD to guide initiation of statin therapy for primary prevention Adults age 40 to 75 years of age without clinical ASCVD or DM and a 10 yr ASCVD risk > 7.5% should be treated with a moderate to high intensity statin therapy Level of Evidence B A Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

43 ACC/AHA 2013 Blood Cholesterol Guideline: Primary Prevention no DM and LDL-C mg/dl Class IIa Recommendations Reasonable to offer moderate intensity statin to adults 40 to 75 years of age with LDL-C mg/dl, without clinical ASCVD or DM and a 10 year ASCVD risk of 5 to < 7.5% Before initiating statin therapy for primary prevention of ASCVD in adults with LDL-C mg/dl without clinical ASCVD or DM it is reasonable for clinicians and patients to engage in a discussion which considers the potential for ASCVD risk reduction benefits and for adverse effects, for DDIs and patient preference for treatment Level of Evidence B C Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

44 ACC/AHA 2013 Blood Cholesterol Guideline: Primary Prevention no DM and LDL-C mg/dl Class IIb Recommendations Before initiating statin therapy for primary prevention of ASCVD in adults with LDL-C mg/dl without clinical ASCVD or DM it is reasonable for clinicians and patients to engage in a discussion which considers the potential for ASCVD risk reduction benefits and for adverse effects, for DDIs and patient preference for treatment Level of Evidence C Additional Risk Factors: LDL-C > 160 mg/dl or genetic hyperlipidemia; Family hx ASCVD in father < 55 yrs of age or mother < 65 years of age; hscrp > 2 mg/dl, CAC score > 300 Agatston units or > 75 percentile for age, sex, and ethnicity; ABI < 0.9; or lifetime risk of ASCVD Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

45 AFCAPS/TexCAPS Randomized, double-blind, placebo-controlled trial in 5,608 men and 997 women with no history of CHD (primary prevention) Baseline LDL-C was 150 mg/dl and HDL-C was 37 mg/dl Randomized, double-blind to lovastatin mg daily (titrated to achieve an LDL-C of <110 mg/dl) or placebo Primary endpoint: First Acute Major Coronary Event (unstable angina pectoris, fatal or non-fatal MI, or sudden cardiac death) Downs JR, et al. JAMA. 1998;279:

46 Downs JR, et al. JAMA. 1998;279: AFCAPS/TexCAPS: Primary Endpoint Results 0.06 Cumulative Incidence Placebo Lovastatin 37% Relative Risk Reduction (P<0.001) Years Years of Follow-up

47 Lancet 2003;361: Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)-Lipid Lowering Arm 10,305 patients with multiple CV risk factors including DM, but not CHD Double-blind, randomized to placebo or atorvastatin 10 mg daily for 3.3 yrs Primary Endpoint: Non-fatal MI and fatal CHD Mean baseline LDL 133 mg/dl: Reduced 33% to a mean LDL of 90 mg/dl

48 Lancet 2003;361: ASCOT-LLA: Primary End Point of 4 Nonfatal MI and Fatal CHD Proportion of Patients (%) Placebo Year Atorvastatin 36% Relative Risk Reduction P=0.0005

49 Major CV Events at Different Levels of Risk Baseline Risk Categories in Primary Prevention Events (% per year) Statin/ Control/ more statin Less (n=1904) (n=2425) Risk ratio & 95% CI < 5% 148 (0.35%) 229 (0.53%) 0.61 ( ) > 5% to < 10% > 10% to < 20% > 20% to < 30% > 30% 487 (1.02%) 716 (1.53%) 854 (2.52%) 1003 (2.98%) 294 (4.40%) 351 (5.28%) 121 (7.29%) 126 (8.16%) 0.66 ( ) 0.82 ( ) 0.81 ( ) 0.83 ( ) Subtotal 1904 (1.44%) 2425 (1.84%) 0.75 ( ) Statin/more statin Control/ Less Cholesterol Treatment Trialists Collaboration. Lancet 2012;380:

50 No Clinical ASCVD Not currently on cholesterol-lowering drugs Initial evaluation prior to statin initiation Fasting lipid panel ALT Hemoglobin A1c (if diabetes status unknown) CK (if indicated) Consider evaluation for other secondary causes or conditions that may influence statin safety Evaluate and Treat Laboratory Abnormalities 1. Triglycerides 500 mg/dl 2. LDL C 190 mg/dl Secondary causes If primary, screen family for FH 3. Unexplained ALT >3X ULN Assign to statin benefit group Counsel on healthy lifestyle habits Diabetes and age y OR LDL C 190 mg/dl No Diabetes age y, and LDL C mg/dl Yes Estimate 10-y ASCVD Risk with Pooled Cohort Equations No >7.5% 10-y ASCVD risk 5%-<7.5% 10-y ASCVD risk <5% 10-y ASCVD risk Age <40 or >75 y and LDL-C < 190 mg/dl Clinicians and patients should engage in a discussion of the potential for: 1. ASCVD risk reduction benefits 2. Adverse effects 3. Drug-drug interactions 4. Patient preferences In selected individuals, additional factors may be considered to inform treatment decision making Initiate statin therapy Re-emphasize healthy lifestyle habits Monitor statin therapy Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

51 Lipid-Lowering Therapies Statins (atorvastatin, fluvastatin, lovastatin, pravastatin, pitavastatin, rosuvastatin, simvastatin) Bile acid sequestrants (colesevelam, cholestyramine, colestipol) LDL-C HDL-C TG 18-63% 5-15% 7-30% 15-30% 3-5% 0 or Nicotinic acid 5-25% 15-35% 20-50% Fibric acid derivatives (gemfibrozil, fenofibrate) Cholesterol absorption inhibitor (ezetimibe) Omega-3 fatty acids (Rx strength) 5-20% or 10-20% 20-50% 18% 1% 7%? 9% 45% Executive summary of NCEP ATP III. JAMA. 2001; 285: ; Crestor package insert. Astra-Zeneca, 2009; Zetia package insert. Merck/Schering-Plough Pharmaceuticals, 2009; Lovaza package insert. GlaxoSmithKline, 2009; Livalo package insert. Kowa Pharmaceuticals America, 2010.

52 Assess medication and lifestyle adherence Fasting lipid panel Yes Anticipated therapeutic response? No Indicators of anticipated therapeutic response and adherence to selected statin intensity: High-intensity statin therapy reduces LDL C approx. 50% from the untreated baseline Moderate-intensity statin therapy reduces LDL C approx. 30% to <50% from the untreated baseline. Reinforce continued adherence Follow-up 3-12 mo Less-than-anticipated therapeutic response Yes Anticipated therapeutic response? Intolerance to recommended dose of statin therapy Yes Management of statin intolerance No Reinforce improved adherence Increase statin intensity OR Consider addition of nonstatin drug therapy No Reinforce medication adherence Reinforce adherence to intensive lifestyle changes Exclude secondary causes of hypercholesterolemia Follow-up 4-12 wk & thereafter as indicated Follow-up 4-12 wk Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

53 ACC/AHA 2013 Blood Cholesterol Guideline: Safety Recommendations Moderate-intensity statin therapy should be used in individuals in whom high-intensity statin therapy would otherwise be recommended when characteristics predisposing them to statin associated adverse effects are present Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

54 ACC/AHA 2013 Blood Cholesterol Guideline: Characteristics Predisposing Individuals to Statin Adverse Effects Multiple or serious comorbidities Previous statin intolerance or muscle disorders Unexplained ALT elevations >3 times ULN Patient characteristics or concomitant use of drugs affecting statin metabolism >75 years of age Additional characteristics: History of hemorrhagic stroke and Asian ancestry Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

55 ACC/AHA 2013 Blood Cholesterol Guideline: Statin Safety Recommendations Individuals receiving statin therapy should be evaluated for new-onset diabetes mellitus and those who develop diabetes mellitus during statin therapy should engage in CV risk reduction lifestyle modifications and continue statin therapy to reduce their risk of ASCVD Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

56 ACC/AHA 2013 Blood Cholesterol Guideline: Statin Safety Recommendations Serum creatine kinase (CK) values should not be routinely measured in individuals receiving statin therapy During statin therapy, it is reasonable to measure CK in individuals with muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or generalized fatigue Decreasing the statin dose may be considered when 2 consecutive values of LDL C levels are <40 mg/dl Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

57 ACC/AHA 2013 Blood Cholesterol Guideline: Statin Safety Recommendations Mild-moderate muscle symptoms during statin therapy: Discontinue the statin until the symptoms can be evaluated. Evaluate the patient for other conditions that might increase the risk for muscle symptoms If muscle symptoms resolve, and if no contraindication exists, give the patient the original or a lower dose of the same statin to establish a causal relationship between the muscle symptoms and statin therapy If a causal relationship exists, discontinue the original statin. Once muscle symptoms resolve, use a low dose of a different statin. Once a low dose of a statin is tolerated, gradually increase as tolerated. If, after 2 months without statin treatment, muscle symptoms or elevated CK levels do not resolve completely, consider other causes If persistent muscle symptoms are determined to arise from a condition unrelated to statin therapy, or if the predisposing condition has been treated, resume statin therapy at the original dose. Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

58 Treatment Strategies in Patients with Statin Intolerance The Cleveland Clinic experience Retrospective analysis of 1,605 patients referred for statin intolerance 72.5% were able to tolerate a statin Intermittent statin dosing (n=149) had lower LDL- C reduction compared with daily dosing (n=1014): 21.3 vs 27.7% (P<0.04) Trend toward a decrease in all-cause mortality at 8 years for patients on daily/intermittent statin dosing compared with those who discontinued statin (P=0.08) Am Heart J 2013;166:

59 ACC/AHA 2013 Blood Cholesterol Guideline: Nonstatin Drugs The panel could find no data supporting the routine use of nonstatin drugs combined with statin therapy to reduce further ASCVD events In individuals who are candidates for statin treatment but are completely statin intolerant, it is reasonable to use nonstatin cholesterollowering drugs that have been shown to reduce ASCVD events in RCTs if the ASCVD riskreduction benefits outweigh the potential for adverse effects. Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

60 Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes (AIM-HIGH) Double-blind trial in 3414 patients with CVD treated with statin therapy to LDL-C of mg/dl Randomized to placebo or extended-release niacin ( mg daily) Primary endpoint: Composite CV events Clinical trial was stopped at 3 years, 18 months earlier than planned N Engl J Med 2011;365:

61 AIM-HIGH: Results Incidence of Primary Endpoint Statin plus placebo: 16.2% Statin plus niacin: 16.4% p=0.80 At Year 3 Baseline Niacin Placebo LDL-C (mg/dl) HDL-C (mg/dl) Triglycerides (mg/dl) N Engl J Med 2011;365:

62 Merck Announces HPS2-THRIVE Study of TREDAPTIVE (Extended Release Niacin/Laropiprant) Did Not Achieve Primary Endpoint 25,673 patients considered to be at high risk for cardiovascular events The combination of ER niacin and laropiprant to statin therapy did not significantly further reduce the risk of the combination of coronary deaths, non-fatal heart attacks, strokes or revascularizations compared to statin therapy

63 ACCORD Study: Combination Lipid Therapy 5518 patients with type 2 diabetes treated with open-label simvastatin randomized to fenofibrate or placebo for 4.7 yrs. Primary outcome: nonfatal MI, nonfatal stroke, or CV death Baseline End of Study Fenofibrate Placebo LDL-C (mg/dl) HDL-C (mg/dl) Triglycerides (mg/dl) Ginsberg HN, et al. N Engl J Med. 2010; 362:

64 ACCORD Study: Results Patients with Primary Endpoint (%) P= Placebo Fenofibrate Subgroup analyses: Possible benefit for men and possible harm for women Possible benefit in patients with both high baseline triglycerides ( 204) and a low baseline HDL-C ( 34) P=0.057 for interaction Ginsberg HN et al. N Engl J Med. 2010; 362:

65 Baigent C, et al. Lancet 2011; 377: The Study of Heart and Renal Protection (SHARP) 9438 patients with chronic kidney disease Not on dialysis: elevated creatinine on 2 occasions 1.7 mg/dl (men) or 1.5 mg/dl (women) On dialysis: hemodialysis or peritoneal dialysis Age 40 years with no history of MI or coronary revascularization Randomized to Ezetimibe/Simvastatin10/20 mg, simvastatin 20 mg alone, or placebo for 1 year to assess safety; after 1 year, simvastatin alone randomized to one of the other two groups Total median follow-up was 4.9 years

66 Baigent C, et al. Lancet 2011; 377: SHARP - Primary Endpoint Results: Major Atherosclerotic Events Proportion with Event (%) Placebo Ezetimibe/Simvastatin Years of follow-up 17% Relative Risk Reduction P= Risk ratio 0.83 ( )

67 Baigent C, et al. Lancet 2011; 377: SHARP: Major Vascular Events Event Ezetimibe/ Simvastatin (n=4650) Placebo (n=4620) Risk ratio & 95% CI Major vascular event 701 (15.1%) 814 (17.6%) Major atherosclerotic event 526 (11.3%) 619 (13.4%) Non-dialysis (n=6247) 296 (9.5%) 373 (11.9%) Dialysis (n=3023) 230 (15.0%) 246 (16.5%) Note: No significant heterogeneity between non-dialysis and dialysis patients (p=0.25) Ezetimibe/ Simvastatin better Placebo better

68 ACC/AHA 2013 Blood Cholesterol Guideline: Additional Recommendations The panel makes no recommendations regarding the initiation or discontinuation of statins in patients with NYHA Class II-IV ischemic systolic heart failure or in patients on maintenance hemodialysis Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.

69 Parting Thoughts. 4 evidence based statin benefit groups Statin intensity is clinically important High-priority research areas to evaluate evidence gaps: Primary prevention in patients > 75 years Goals vs fixed-dose statin therapy Low-intensity statin plus nonstatin in statinintolerant patients New onset diabetes with statin therpay Role of new and emerging drug therapies

70

71 National Heart Lung and Blood Institute: Systematic Evidence Reviews in Development Director's Corner Message: NHLBI adopts new collaborative partnership model for clinical practice guidelines development Blood Pressure Draft Finished Federal Review Expert Review Advisory Council HHS Clearance Partnerships Formed Completed Completed Completed Completed Pending Ongoing Partner Release Cholesterol Completed Completed Completed Completed Pending Ongoing ACC/AHA Obesity Completed Completed Completed Completed Pending Ongoing ACC/AHA Lifestyle Completed Completed Completed Completed Pending Ongoing ACC/AHA Risk Assessment Completed Completed Completed Completed Pending Ongoing ACC/AHA Last Updated November

72 THE WRITING ON THE WALL.. COMMENTARY JNC 8 Transmogrified Barry J. Matterson, MD, MBA J Clin Hypertens 2013;10:704.

73 JNC 8 Original Critical Questions Among adults with hypertension, does initiating antihypertensive pharmacologic therapy at specific BP thresholds improve health outcomes? Among adults, does treatment with an antihypertensive pharmacological therapy to a specified BP goal lead to improvements in health outcomes? In adults with hypertension, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes?

74 NIH: National Heart Lung and Blood Institute Blood Pressure in Adults: Systematic Evidence Review from the Hypertension Expert Panel Status of Systematic Review to Enable Guideline Development Final editing stage Expected Release Date: January, 2014 Background Guideline Executive Committee Policy for Managing Potential Conflicts of Interest and Relationships with Industry Expert Panel Members Last Updated November

75 SO WHAT CAME NEXT.. Tuesday December 17, 2013 Clinical Practice Guidelines for the Management of Hypertension in the Community A Statement by the American Society of Hypertension (ASH) and the International Society of Hypertension (ISH) Wednesday December 18, Evidence-Based Guideline for the Management of High Blood Pressure in Adults Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8) J Hypertens 2014 Jan;32(1):3-15 JAMA. doi: /jama

76 ASH/ISH Clinical Practice Guidelines Written to provide a straightforward approach to managing hypertension in the community Brief curriculum with set of recommendations for primary care physicians, medical students, and all professionals who are hands-on practitioners Acknowledge that there are insufficient published data from clinical trials in hypertension to create recommendations that are completely evidence-based, and so inevitably some recommendations reflect expert opinion and experience J Hypertens 2014 Jan;32(1):3-15

77 ASH/ISH: General Recommendations Age < 80 years: Goal BP is usually <140/90 mm Hg Past guidelines recommended <130/80 mm Hg for diabetes, chronic kidney disease (CKD), and coronary artery disease; however, evidence to support this lower target in patients with these conditions is lacking Some experts still recommend <130/80 mm Hg if albuminuria is present in CKD Age 80 years: Threshold for starting and target for treatment is 150/90 mmhg (if CKD or diabetes, consider <140/90 mm Hg) J Hypertens 2014 Jan;32(1):3-15

78 Antihypertensive Pharmacotherapy Traditional First-Line Agents Angiotensin Converting Enzyme Inhibitor (ACEi) Angiotensin Receptor Blocker (ARB) Beta-Blocker Calcium Channel Blocker (CCB) Diuretic (typically a thiazide) Common Alternative Agents Aldosterone Antagonist (e.g., spironolactone) Alpha Antagonist (i.e., terazosin) Centrally Acting Alpha Agonist (i.e., clonidine) Direct Arterial Vasodilator (i.e., hydralazine) Direct Renin Inhibitor (i.e., aliskiren) Reserpine

79 ASH/ISH Guideline J Hypertens 2014 Jan;32(1):3-15

80 ASH/ISH: Drug Therapy for Hypertension with Other Conditions First Drug Diabetes Mellitus Chronic Kidney Disease ACEI, or ARB (Note: In Black patients CCB or Thiazide is acceptable) ACEI, or ARB (Note: In Black patients good evidence with ACEI CAD Beta-blocker plus ACEI or ARB Prior Stroke ACEI or ARB Heart Failure ACEI (or ARB) plus beta-blocker plus diuretic plus spironolactone Regardless of blood pressure if symptomatic J Hypertens 2014 Jan;32(1):3-15

81 JNC 8 Report..these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient. Over 3 years to come up with final document Only randomized studies reporting effects of studied interventions on important health outcomes (eg., mortality, CV events) were included Evidence Quality rating (High, Moderate or Low) and Strength of Recommendation assigned to 11 final recommendations JAMA. doi: /jama

82 JNC 8 Report: General Recommendations Age 60 years: initiate pharmacologic treatment at BP 150/90 mmhg and treat to a goal <150/90 mm Hg (Strong Recommendation Grade A) if pharmacologic treatment results in lower achieved SBP (e.g., <140 mm Hg) and treatment is well tolerated and without adverse effects on health or quality of life, treatment does not need to be adjusted. (Expert Opinion Grade E) Age < 60 years: initiate pharmacologic treatment to lower BP at 140/90 mmhg and treat to a goal BP<140/90 mmhg (DBP: For ages years, Strong Recommendation Grade A. DBP: For ages years. SBP: Expert Opinion Grade E)Age JAMA. doi: /jama

83 JNC 8 Report JAMA. doi: /jama

84 JNC 8 Report: Strategies to Dose Antihypertensive Agents Strategy Description Comments A B C Start one drug, titrate to maximum dose, and then add a second drug Start one drug and then add a second drug before achieving maximum dose of the initial drug Begin with 2 drugs at the same time, either as 2 separate pills or as a single pill combination Use thiazide-type diuretic, CCB, ACEI, or ARB May minimize side effects Some recommended starting with 2 drugs when SBP >160 mm Hg and/or DBP >100 mm Hg (or if BP >20/10 mm Hg above goal) Always avoid combined use of an ACEI with ARB JAMA. doi: /jama

85 Critique of Both Guidelines ASH-ISH Pro For practicing clinicians in a variety of settings Addresses diagnostics and other aspects of managing hypertension Addresses comorbid conditions Con Clinical recommendations are not ranked based on evidence JNC 8 Report Pro Purely evidence based review process Exhaustive review utilizing an overall academic approach Con Took multiple years to complete 6 of the 11 recommendations are based on Expert Opinion Only commented only on 2 comorbid conditions (diabetes and CKD) Up to 100 mg of HCTZ J Hypertens 2014 Jan;32(1):3-15 JAMA. doi: /jama

86 Common Themes.

87 Antihypertensive therapy reduces risk of CV events in patients with elevated BP!

88 A Cochrane Collaboration (2007): Beta-Blockers for Hypertension 13 randomized trials in 91,561 patients Beta-blocker vs. Relative Risk (95% CI) CV Disease Stroke Death Placebo 0.88* ( ) 0.80* ( ) 0.99 ( ) Thiazide 1.13 ( ) 1.17 ( ) 1.04 ( ) ACEI/ARB 1.00 ( ) 1.30* ( ) 1.10 ( ) CCB 1.18* ( ) 1.24* ( ) 1.07 ( ) CochraneDatabase of Systematic Reviews 2007, Issue 1. Art.No.:CD

89 N Engl J Med 2008;358: Hypertension in the Very Elderly Trial (HYVET) 3845 patients 80 yrs with hypertension Randomized, double-blind, to: Placebo or Perindopril +/- Indapamide Stopped early after 1.8 years Patients (%) Placebo Primary Endpoint: Stroke Drug Therapy Secondary Endpoint: Mortality P=0.06 P=0.02

90 Blood Pressure (mmhg) HYVET Results Follow-up (years) Placebo Drug Therapy Target BP = 150/80 mm Hg N Engl J Med 2008;358:

91 Journal of Hypertension 2013, 31: Thiazide diuretics Beta-blockers Angiotensin Receptor Blockers Other Antihypertensives Calcium Channel Blockers ACE Inhibitors Preferred Combinations Useful Combination with limitations Possible but less well tested Not Recommended

92 Differences and Omissions.

93 Incongruence Among Guideline Six other guideline since 2010: ADA (2014), ESH/ESC (2013), CHEP (2013), KDIGO (2012), NICE (2011), ISHIB (2010) Differences among recommended BP goals in individual patients: <150/90, < or 140/90, <140/85, <140/80, <135/85, <130/85, < or 130/80 mmhg Inconsistent use of terms diuretic, thiazide, thiazide-type JAMA. doi: /jama

94 Select Recommendations NICE: Primary Hypertension in Adults If diuretic treatment is to be initiated or changed, offer a thiazide-like diuretic: Chlorthalidone ( mg once daily) or indapamide (1.5 mg modified-release or 2.5 mg once daily) in preference to a conventional thiazide diuretic such as bendroflumethiazide or hydrochlorothiazide For people who are already having treatment with bendroflumethiazide or hydrochlorothiazide and whose BP is stable and well controlled, continue treatment

95 A Tale of Two Thiazides Hydrochlorothiazide Chlorthalidone Category Thiazide-type Thiazide-like Half-life (hrs) Antihypertensive equivalency Utilization Prescribed more frequently In most combination products Evidence-base Hypokalemia/ Hyponatremia Not used in most landmark trials Moderate concern 25 mg mg Preferred agent in resistant hypertension Extensive use in landmark clinical trials (e.g., SHEP, ALLHAT) Slightly higher in elderly patients N Engl J Med 2009;361: J Am Coll Cardiol 2011;57: Ann Intern Med. 2013;158:

96 Kidney International Supplements (2012) 2, 340; doi: /kisup Kidney Disease Improving Global Outcomes CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF BLOOD PRESSURE IN CHRONIC KIDNEY DISEASE

97 KDIGO: Albuminuria Influences Treatment Chronic Kidney disease, non-dialysis patients Urine Albumin BP Goal Treatment Excretion per 24 hrs (mm Hg) < 30 mg 140/90 Not specified 30 to 300 mg 130/80 ACE-I or ARB > 300 mg 130/80 ACE-I or ARB Same suggestions and recommendations provided for patients with diabetes and without, but different cited level of evidence Kidney International Supplements (2012) 2,

98 KDIGO: Kidney Transplant Patient Recommendations In adult kidney transplant recipients, treat to maintain a BP consistently 130/80 mm Hg, irrespective of the level of urine albumin excretion In adult kidney transplant recipients, choose a BP-lowering agent after taking into account the time after transplantation, use of calcineurin inhibitors, presence or absence of persistent albuminuria, and other co-morbid conditions Kidney International Supplements (2012) 2,

99 ADA Position Statement STANDARDS OF MEDICAL CARE IN DIABETES 2014 Diabetes Care 2014;37 (Suppl 1): s14-s80.

100 Recommendations & Level of Evidence ADA: Hypertension/Blood Pressure Control Goals Treat to a systolic BP goal of < 140 mmhg (B) Lower systolic targets (e.g., < 130 mmhg), may be appropriate for certain patients (e.g., younger), if achieved without undue treatment burden (C) Treat to a diastolic BP < 80 mmhg (B) Diabetes Care 2013;36 (Suppl 1): s11-s66.

101 Hypertension Optimal Treatment (HOT) Trial: Major Cardiovascular Events at 4 yrs Events per 1000 patient years All Patients (n=18,790) P=0.5 Patients with Diabetes (n=1501) P=0.005 <90 <85 <80 <90 <85 <80 Diastolic BP Goal Lancet 1998;351:

102 Parting Thoughts General goal of <140/90 mm Hg for most patients Beta-blockers are not first-line agents Race advocated to influence selection of drug therapy Many similarities with new guidelines, but significant yet subtle differences

103 Patient Cases 50-year-old African American man has hypertension. His a smoker. Despite lifestyle modifications for 6 months, BP is 156/96 mm Hg. TC = 205 mg/dl, HDL-C = 40 mg/dl, LDL-C = 120 mg/dl, triglycerides = 225. No chronic medications. 70-year-old woman with hypertension, CHD (s/p MI), dyslipidemia. Adherent with atorvastatin 20 mg daily, carvedilol 25 mg twice daily and lisinopril 40 mg daily. BP is 144/90 mm Hg. No fasting lipid panel available. 60-year-old white man with hypertension and type 2 diabetes. Adherent with amlodipine 10 mg daily, HCTZ 25 mg daily, and ezetimibe/simvastatin 10/10 mg daily. BP is 128/78 mm Hg, LDL-C is 65 mg/dl. How should these patients be treated?

104 Challenges "Drugs don't work in patients who don't take them." Former U.S. surgeon general C. Everett Koop

105 Barriers to Medication Adherence Patient-Related Barriers Complexity of medication regimen High out-of-pocket cost Concern or risk of side effects Receives contradictory information from healthcare providers Belief system that is inconsistent with contemporary medicine Prescriber-Related Barriers Limited time with the patient Uncomfortable speaking to patients about adherence Lack of incentive to spend additional time counseling on adherence Unaware of lower-cost medications Pharmacist-Related Barriers Difficulties communicating with Prescriber Limited time to review medication refill histories Inability to access refill history across multiple pharmacies Limited access to patient s medical records in the ambulatory setting Adapted from: Clinician's Toolkit: A Guide to Medication and Lifestyle Adherence. National Lipid Association. Available at:

106 Interventions to Improve Adherence S I M Simply the regimen Impart knowledge Modify patient beliefs and human behavior P Provide communication and trust Adjust timing, frequency, and dosage Utilize once-daily medications whenever possible Encourage the use of adherence aids (e.g., pillboxes, cell phone alarms) Consider each patient s activities of daily living (e.g., swing shift workers) Patient-provider shared decision making Provide clear instructions and expectations for all prescriptions Involve relatives or caregivers when discussing medications Recommend electronic education formats (e.g., video, websites) Ask patient about their needs and what might help them adhere to therapy Ensure patient understands consequences of non-adherence Addressed perceived barriers of taking the medication Provide rewards for adherence (e.g., praise, coupons, fewer clinic visits) Practice to improve interviewing skills Embrace active listening and provide emotional support Elicit patient s input when discussing treatment options Allow adequate time for the interaction and encourage patient to ask questions Foster a greater understanding of health literacy and how it affects patients L Leave the bias Ensure communication style is patient-centered Take extra time to understand and overcome cultural barriers E Evaluate adherence Tailor education to the patient s level of understanding Ask patients simply and directly about adherence Engage patients about adherence at every encounter Measure drug levels or efficacy parameters, when applicable Review medication containers, noting last fill date and remaining medicine Adapted from: Clinician's Toolkit: A Guide to Medication and Lifestyle Adherence. National Lipid Association. Available at: