Speaker Disclosure. Pharmacist Objectives. Path to New Hypertension (HTN) Guidelines. Overview of New HTN Guidelines 8/21/2014

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1 Speaker Disclosure Erica Pearce, Pharm.D. declares no conflicts of interest, real or apparent, and no financial interests in any company, product, or service mentioned in this program, including grants, employment, gifts, stock holdings, and honoraria. Erica Pearce, Pharm.D., BCPS, BCACP Jennifer Rosselli, Pharm.D., BCPS, BCACP Jennifer Rosselli, Pharm.D. declares no conflicts of interest, real or apparent, and no financial interests in any company, product, or service mentioned in this program, including grants, employment, gifts, stock holdings, and honoraria. Pharmacist Objectives At the conclusion of this program, the pharmacist will be able to: Identify thresholds for initiating antihypertensive and lipidlowering pharmacotherapy. Select treatment goals for patients taking antihypertensive and lipid-lowering therapy. Design individualized patient treatment plans for hypertension and to reduce cardiovascular disease risk. Erica Pearce, Pharm.D., BCPS, BCACP Assistant Professor of Pharmacy Practice, Division of Ambulatory Care St. Louis College of Pharmacy Clinical Pharmacist SLUCare Department of Family and Community Medicine Path to New Hypertension (HTN) Guidelines National Heart, Lung, and Blood Institute (NHLBI) established the Eight Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC8) in 2008 NHLBI discontinued development of all guidelines in June 2013 JNC8 panel elected to independently publish their report 2014 Evidence-Based Guideline for Management of High Blood Pressure in Adult Published in February 2014 Limited to review of RCTs published through August 2013 Overview of New HTN Guidelines Focused recommendations on Blood pressure (BP) thresholds for treatment BP goals for treatment Preferred drug therapy NO change in definition or staging of HTN Lifestyle modifications (LSM) recommendations detailed separately 2013 AHA/ACC Guidelines on Lifestyle Management to Reduce Cardiovascular Risk Circulation. 2014; 129: S76-S99. 1

2 JNC 8 Initiation of Drug Therapy Initiate drug therapy when the patient s BP is above their BP goal Should be above goal on more than 1 day JNC 8 BP Goals Patient Population BP Goal (mm Hg) General population > 60 years < 150/90 General population < 60 years < 140/90 Diabetes (DM) < 140/90 Chronic Kidney Disease (CKD) < 140/90 Comparison of BP goals DM JNC8: <140/90 mm Hg ADA: <140/80 mm Hg or <130/80 mm Hg CKD JNC8: <140/90 mm Hg KDIGO: <140/90 mm Hg (no proteinuria) <130/80 mm Hg (with proteinuria) Blacks JNC8: same a general population ISHIB: <135/85 mm Hg <130/80 mm Hg (with target organ damage) Question #1 A 67 year White female has a past medical history of coronary artery disease with myocardial infarction in 2011, diabetes and GERD. She comes to the pharmacy for her MTM appointment with her latest lab results. SCr 1.2 mg/dl, A1c = 8.3%, GFR = 70 ml/min, CrCl =68 ml/min, urine microalbumin:creatinine ratio = 11 Based on JNC8, what is this patient s BP goal? A. <150/90 mm Hg B. <140/90 mm Hg C. <130/90 mm Hg D. <130/80 mm Hg Diabetes Care 2014;37(1):S14-S80. Kidney Int Suppl. 2012;2(5): Hypertension 2010;56(5) JNC 8 Drugs of First Choice General, nonblack and DM population Thiazide-type diuretics Calcium channel blocker (CCB) Angiotensinconverting enzyme inhibitor (ACEI) Angiotensin receptor blocker (ARB) General, black population Thiazide-type diuretics CCB CKD population ACEI or ARB JNC 8 Recommended Medications Medication Initial Daily Dose (mg) Target Dose (mg) Frequency ACE-Inhibitors Captopril Enalapril Lisinopril Angiotensin receptor blockers Eprosartan Candesartan Losartan Valsartan Irbesartan

3 JNC 8 Recommended Medications Medication Initial Daily Dose (mg) Thiazide-type diuretics Target Dose (mg) Frequency (doses/day) Chlorthalidone Hydrochlorothiazide hi id Indapamide Calcium channel blockers Amlodipine Diltiazem ER Beta-blockers Atenolol Metoprolol JNC 8 Treatment Algorithm: General Population and DM without CKD Nonblack Initiate thiazide-type diuretic, ACEI*, ARB*, and/or CCB *ACEI and ARB should not be used in combination Blood Pressure Not to BP not Goal to Goal Black Initiate thiazide-type diuretic, and/or CCB Select a medication adjustment strategy and continue to adjust doses of medications and/or add on additional medications* until BP is controlled. JNC 8 Treatment Algorithm: CKD with or without DM Blood Pressure Not to BP not Goal to Goal All races Initiate ACEI or ARB, alone or in combination with another drug class* Medication Adjustment Strategies A B Start one HTN medication at low-dose Titrate to max dose Then add another HTN medication Start one HTN medication at low-dose Add a second HTN medication Titrate dose(s) of the medications Select a medication adjustment strategy and continue to adjust doses of medications and/or add on additional medications until BP is controlled. C Start with 2 HTN medications Recommended in Stage 2 HTN *ACEI and ARB should not be used in combination AHA/ACC/CDC American Heart Association (AHA), American College of Cardiology (ACC), Centers for Disease Control and Prevention (CDC) An Effective Approach to High Blood Pressure Control Development of a treatment algorithm Published in April 2014 Hypertension 2014;63(4): AHA/ACC/CDC Treatment Algorithm BP /90-99 mm Hg Lifestyle modification Consider thiazide-type diuretic 3 months BP at goal? No BP >160/>100 mm Hg Lifestyle modification Thiazide-type diuretic + ACEI, ARB, or CCB ACEI + CCB 2-4 weeks Initiate drug therapy, thiazide-type diuretic for most If currently on BP med, titrate dose(s) or add drug from another class* *ACEI and ARB should not be used in combination Hypertension 2014;63(4): Yes Continue current therapy 3

4 AHA/ACC/CDC Treatment Algorithm BP at goal? No 2-4 weeks Optimize dosage(s) or add drug from another class* Consider secondary causes of HTN Address adherence, encourage home BP monitoring Consider referral to HTN specialist Yes Continue current therapy Question #2 A 46 year old Black female returns to follow-up on elevated BP. At her last appointment (3 months ago) her BP was 154/96 mm Hg. Her BP today is 148/94 mm Hg despite following the DASH diet and cutting back on caffeine. Which of the following HTN medication(s) would your recommend the physician begin today? A. Amlodipine 5 mg PO daily B. Losartan 100 mg PO daily C. Lisinopril 10 mg PO daily D. Hydrochlorothiazide 50 mg PO daily *ACEI and ARB should not be used in combination Hypertension 2014;63(4): Comparing the Treatment Algorithms JNC8 Drugs of first-choice Thiazide-type diuretic ACEI ARB CCB Selection of therapy Three different strategies Follow-up monitoring No specific timing recommendation ACC/AHA/CDC Drugs of first-choice Thiazide-type diuretic ACEI ARB CCB Selection of therapy Based on HTN stage Follow-up monitoring 2-4 weeks following a drug initiation/ adjustment Hypertension 2014;63(4): Dosing Time: MAPEC Trial Ambulatory Blood Pressure Monitoring for Prediction of Cardiovascular Events (MAPEC) Prospective RTC Evaluated dosing all HTN medications in the AM vs. at least 1 HTN medication at bedtime n=2156 BP evaluated via 48 hour ambulatory BP monitor Primary outcome: CVD morbidity and mortality Chronobiol Int 2010;27(8) MAPEC Trial Results No significant difference in groups at baseline Mean follow-up: 5.6 years Outcome Event # in AM dosing Event # in PM dosing p-value Total events <0.001 Total death Cardiovascular death CVD events <0.001 Cerebrovascular events <0.001 Heart failure 33 8 <0.001 Chronobiol Int 2010;27(8) Summary Drug therapy should be initiated when BP is consistently above goal JNC8 BP goals are less aggressive <140/90 mm Hg for most ACEI, ARB, CCB have been added to thiazidetype diuretics as the drugs of first choice Consider dosing one HTN medication at bedtime Hypertension 2014;63(4): Chronobiol Int 2010;27(8)

5 Jennifer Rosselli, Pharm.D., BCPS, BCACP Clinical Assistant Professor Southern Illinois University Edwardsville, School of Pharmacy Ambulatory Care Clinical Pharmacy Specialist Southern Illinois Healthcare Foundation Previous Cholesterol Guidelines (ATP III) Risk category LDL goal (mg/dl) LDL level to initiate TLC (mg/dl) LDL level to consider drug therapy (mg/dl) CHD or CHD risk equivalents < 100 (< 70 optional) > 100 > 100 (<100 consider (10-year risk > 20%) drug options) 2+ risk factors (10-year risk 10-20%) < 130 (< 100 optional) > 130 > 130 ( consider drug options) 2+ risk factors < 130 > 130 > 160 (10-year risk < 10%) 0-1 risk factor < 160 > 160 > 190 ( drug optional) JAMA. 2001;285: Circulation. 2004;110: Path to New Cholesterol Guidelines NHLBI ATP IV Panel established in 2008 Limited to review of RCTs, systematic reviews, and meta-analyses published through July 2013 Transitioned to ACC/AHA guideline Expert Panel in June 2013 All 16 members of NHLBI ATP 23 expert reviewers Representative of federal agencies Overview of New Cholesterol Guidelines No specific LDL and/or non-hdl targets Reduced role of non-statin therapies Target is reducing atherosclerotic cardiovascular disease (ASCVD) risk Coronary heart disease Stroke Peripheral arterial disease Pooled Cohort Equations for primary prevention Still 4 treatment target groups, but categorized differently Lifestyle Modification (LSM) Emphasize LSM as critical component of ASCVD risk reduction and overall health Heart healthy diet (DASH, USDA Food Pattern, or AHA diet) Exercise Tobacco avoidance Maintain healthy weight LSM recommendations detailed separately (2013 Lifestyle Management Work Group Guideline) All Things Statin (HMG CoA Reductase Inhibitors) Recommendations specific to use of statins at fixed-doses Statin RCTs provide extensive evidence of ASCVD event reduction Focus on appropriate intensity of statin therapy in those most likely to benefit 4 treatment target groups categorized as major statin benefit groups Circulation. 2014;129:S76-S99. 5

6 Statin Benefit Group #1: ASCVD No High-intensity Clinical ASCVD Age > 75 years Yes Moderateintensity statin therapy History of myocardial infarction Acute coronary syndrome Stable or unstable angina Arterial revascularization (coronary or other) Stroke or TIA Peripheral arterial disease Intensity of Statin in Secondary Prevention TNT study Design Subjects Intervention Outcomes Follow-up Major CV event rate Randomized, doubleblind, control trial Clinical CHD (n=10,001) atorvastatin 10 mg or 80 mg 1 st major CV event 4.9 years (median) atorva 10 mg = 10.9% atorva 80 mg = 8.7% HR 0.78 (95% CI 0.69 to 0.89) PROVE-IT TIMI 22 study Design Subjects Intervention Outcomes Follow-up Death or major CV event rate Randomized, doubleblind, control trial ACS within 10 days (n=4,162) pravastatin 40 mg or atorvastatin 80 mg All-cause mortality, major CV event, revascularization months prava 40 mg = 26.3% atorva 80 mg = 22.4% RR 16% (95% CI 5% to 26%) N Engl J Med. 2005;352: N Engl J Med. 2004;350: Statin Benefit Group #2: LDL > 190 mg/dl Statin Benefit Group #3: Age years with Diabetes and LDL mg/dl LDL > 190 mg/dl and age > 21 yr DM, age yr, and LDL mg/dl High-intensity Calculate 10-yr ASCVD risk < 7.5% > 7.5% Moderate-intensity High-intensity 10-year ASCVD Risk: Pooled Cohort Equations Use of Pooled Cohort Equations instead of Framingham to estimate 10-year risk Only useful in patients without clinical ASCVD and LDL-c < 190 mg/dl Use the estimated absolute 10-year risk of ASCVD to guide statin initiation in patients not already in a statin benefit group Only need to recalculate in patients not receiving cholesterol-lowering drug therapy every 4-6 years Pooled Cohort Equations Download the calculator at: ssional/statementsguidelines/prev entionguidelines/prevention- Guidelines_UCM_457698_SubHom epage.jsp. Online calculators available Available as a free app for Apple and Android devices 6

7 Limitations of Pooled Cohort Equations Parameters for 10-year risk estimate set at: y/o White and black patients TC values mg/dl HDL values mg/dl SBP mmhg Has not been previously prospectively studied Probably overestimates risk LDL value still not part of the equation Statin Benefit Group #4: Estimated 10-year ASCVD risk > 7.5% 5% to 7.5% Moderate-intensity (Level B evidence) No DM, age yr, and LDL mg/dl Calculate 10-yr ASCVD risk > 7.5% Moderate-to-high-intensity (Level A evidence) Choosing Statin Therapy High-Intensity LDL reduction of > 50% on average atorvastatin 80 mg rosuvastatin 20 mg atorvastatin 40 mg* rosuvastatin 40 mg* Moderate-Intensity LDL reduction of 30-50% on average atorvastatin 10 mg rosuvastatin 10 mg simvastatin mg pravastatin 40 mg lovastatin 40 mg fluvastatin 40 mg BID atorvastatin 20 mg* rosuvastatin 5 mg* pravastatin 80 mg* fluvastatin XL 80 mg* pitavastatin 2-4 mg* Low-Intensity LDL reduction of < 30% pravastatin mg lovastatin 20 mg simvastatin 10 mg* fluvastatin mg* pitavastatin 1 mg* *Alternatives with FDA approval but not studied in RCTs reviewed by Expert Panel Question #3 A 67-year old White female with a history of MI, DM, and GERD. TC 181 mg/dl, LDL 74 mg/dl, HDL 74 mg/dl, TG 164 mg/dl, ALT 24 U/L What is this patient s lipid goal per AHA/ACC 2013 cholesterol guidelines? A. Treat to LDL < 70 mg/dl B. Treat with high-intensity statin C. Depends on estimated 10-year ASCVD risk Question #4 A 56-year old Black male with a history of gout, hyperlipidemia, and hypertension presents to an outpatient clinic for routine follow-up of chronic diseases. He has no current complaints. Today s BP 124/78 Current medications: amlodipine 5 mg allopurinol 300 mg pravastatin 20 mg (initiated 6 months ago) Question #4 (Continued) Labs yesterday: TC 236 mg/dl, HDL 71 mg/dl, LDL 135 mg/dl, TG 148 mg/dl 6 months ago: TC 261 mg/dl, HDL 54 mg/dl, LDL 163 mg/dl, TG 220 mg/dl, ALT 14 U/L, BP 118/72, 10-yr ASCVD risk 10.4%, Lifetime ASCVD risk 69% Which is the most appropriate recommendation for his lipid management? A. Switch pravastatin to simvastatin 40 mg B. Obtain ALT to fully evaluate current therapy C. Continue pravastatin 20 mg D. Increase pravastatin to 40 mg 7

8 Approach to Patients Not in a Statin Benefit Group Consider other factors that may guide treatment decision-making LDL > 160 mg/dl Family history of premature ASCVD hsc-reactive protein > 2 mg/l Coronary artery calcium score > 300 Agatston units Ankle-brachial index < 0.9 Elevated lifetime risk of ASCVD Statin Therapy Monitoring Lipid panel 4-12 weeks after initiating statin 3-12 months thereafter unless response isn t as expected Hepatic transaminases (ALT) at baseline and if hepatotoxic symptoms present Creatine kinase CK levels should not be routinely measured Consider at baseline in patients who may be at increased risk of adverse muscle events Reasonable to measure CK if muscle symptoms present Patients Unlikely to Benefit from Statin Therapy Age > 75 years without clinical ASCVD NYHA Class II to IV Maintenance hemodialysis Expert panel makes no recommendations for initiating or discontinuing statins in these patients KDIGO Lipid Guideline recommends against initiating statin in patients with dialysisdependent CKD, continue statin in patients already taking it without tolerability issues Kidney Inter. Suppl. 2013;3: Non-Statin Cholesterol- Lowering Therapies Lack of data supporting routine use Adherence to LSM and should be addressed before addition of non-statin medication Consider use for high-risk patients with Less than anticipated response to statin Inability to tolerate recommended intensity of statin Total statin intolerance When is LDL Too Low? Expert panel did not identify evidence of harm when LDL is < 40 mg/dl on Consider decrease in statin dose when 2 consecutive LDL values are < 40 mg/dl Implications of New Guidelines Data from National Health and Nutrition Examination Surveys (NHANES) used to estimate eligible statin users Compared ATP III vs. new AHA/ACC guidelines Increase in U.S. adults, ages years, eligible for from 37.5% to 48.6% under new guidelines Increase in overall statin use, especially for primary prevention N Engl J Med. 2014;370:

9 Summary Major statin benefit groups Clinical ASCVD present LDL > 190 mg/dl Age years without clinical ASCVD and Diabetes and LDL mg/dl Estimated 10-year ASCVD risk > 7.5% and LDL mg/dl In primary prevention, discuss risk vs. benefits of medication therapy Limited role for non-statin therapies Guidelines are not rules and do not replace clinical judgment Work in pairs to complete the practice case References American Diabetes Association. Standards of Medical Care in Diabetes Diabetes Care. 2014;37(1):S14-S80. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350: Eckel RH, Jakicic JM, Ard JD, et al AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S76-S99. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National l Cholesterol l l Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285: Flack JM, Sica DA, Bakris G, et al. Management of high blood pressure in blacks: an update of the International Society on Hypertension in Blacks. Hypertension 2010;56(5) Go AS, Bauman MA, Coleman King SM, et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension. 2014;63(4): Grundy SM, Cleeman JI, Bairey Merz CN, et al, for the Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110: References (continued) Hermida RC, Ayala DE, Mojon A, Fernandez JR. Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int. 2010;27(8) James PA, Oparil S, Carter BL, et al Evidence-based guidelines for the management of high blood pressure in adults: report from the panel members appointed to the eighth Joint National Committee (JNC 8). JAMA. 2014;311(5): Kidney Disease: Improving Global Outcomes (KDIGO). Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int Suppl. 2012;2(5): KDIGO Lipid Work Group. KDIGO Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease. Kidney Inter. Suppl. 2013;3: LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352: Pencina MJ, Navar-Boggan AM, D'Agostino RB Sr, et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med. 2014;370: Stone NJ, Robinson J, Lichtenstein AH, et al ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. Erica Pearce, Pharm.D., BCPS, BCACP erica.pearce@stlcop.edu Jennifer Rosselli, Pharm.D., BCPS, BCACP jrossel@siue.edu 9