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1 HYPERTENSION UPDATE: NEW JNC 8 Guideline vs OLD Federal Motor Carrier Safety Regulations PLEASE STAND BY WEBINAR WILL BEGIN AT 12:00 PM PST FOR AUDIO: CALL / ACCESS CODE: # Conflict of Interest Disclosure My partner/spouse and I have no financial relationships with commercial entities producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients relevant to the content I am planning, developing, presenting, or evaluating.

2 Content Attestation I, Joel Handler, hereby declare that the content for this activity, including any presentation of therapeutic options, is well balanced, unbiased, and to the extent possible, evidence-based. History of NHLBI CVD Adult Clinical Guidelines Joint National Committee on Prevention, Detection, Evaluation, & Treatment of High Blood Pressure (JNC) JNC 7: 2003 JNC 6: 1997 JNC 5: 1992 JNC 4: 1988 JNC 3: 1984 JNC 2: 1980 JNC 1: 1976 Detection, Evaluation, & Treatment of High Blood Cholesterol in Adults (ATP, Adult Treatment Panel) ATP III Update: 2004 ATP III: 2002 ATP II: 1993 ATP I: 1988 Clinical Guidelines on the Identification, Evaluation, & Treatment of Overweight and Obesity in Adults Obesity 1:

3 Objectives Recognize the JNC 8 recommendations for the treatment of hypertension Have a plan for addressing the hypertension patient adequately treated per JNC 8, but whose blood pressure does not satisfy the current DOT regulation Identify and avoid common errors in blood pressure measurement

4 Trials Included in ESH 2013 NOT included in JNC 8 Trial Comparator Trial Comparator Trial Comparator ACE-I and diuretic combination ACE-I and calcium antagonist combinatio BB and diuretic combination PROGRESS Placebo SystEur Placebo Coope & WarrenderPlacebo ADVANCE Placebo SystChina Placebo SHEP Placebo HYVET Placebo NORDIL BB + D STOP Placebo CAPP BB + D INVEST BB + D STOP 2 ACE-I or CA Angiotensin receptor blocker and diuretic combination ASCOT BB + D CAPPP ACE-I + D ACCOMPLISH ACE-I + D LIFE ARB + D Calcium antagonist and diuretic combination SCOPE D + placebo ALLHAT ACE-I + BB LIFE BB + D Combination of two renin-angiotensin- ALLHAT CA + BB system blockers / ACE-I +ARB or RA blocker + renin inhibitor CONVINCE CA + D FEVER D + placebo ONTARGET ACE-I or ARB NORDIL ACE-I + CA ELSA BB + D ALTITUDE ACE-I or ARB INVEST ACE-I + CA CONVINCE BB + D ASCOT ACE-I + CA VALUE ARB + D Trials in JNC 8 NOT included in ESH 2013 Survey MRC ANBP 2 HDFP UKDPS HOT AASK MDRD REIN-2 INSIGHT KYOTO CASE-J JATOS VALISH VAH

5 Table 14. Compelling and possible contra-indications to the use of antihypertensive drugs Drug Compelling Possible Diuretics (thiazides) Gout Metabolic syndrome Glucose intolerance Pregnancy Hypercalcemia Hypokalemia Beta-blockers Asthma Metabolic syndrome Calcium antagonist (dihydropyridines) Calcium antagonist (verapamil, diltiazem) A-V block (grade 2 or 3) A-V block (grade 2 or 3, trifascicular block) Severe LV dysfunction Heart failure Glucose intolerance Athletes and physically active patients Chronic obstructive pulmonary disease (except for vasodilator betablockers) Tachyarrhythmia Heart failure ACE inhibitors Pregnancy Women with child bearing potential Angioneurotic edema Hyperkalemia Bilateral renal artery stenosis Angiotensin receptor blockers Pregnancy Women with child bearing potential Hyperkalemia Bilateral renal artery stenosis Gout and Thiazide: NEJM Case Vignette A 54 year old male with crystal-proven gout has had 4 attacks during the previous year. On allopurinol 300 mg daily, his serum urate is 7.2 mg/dl. His BP is controlled on HCTZ. How should his case be managed? 1. Increase allopurinol to 400 mg 2. Stop HCTZ 3. Increase allopurinol to 400 mg and stop HCTZ Neoghi T. NEJM 2011; 364:

6 Condition Table 15. Drugs to be preferred in specific conditions Asymptomatic organ damage LVH Asymptomatic atherosclerosis Microalbuminuria Renal dysfunction Clinical CV event Previous stroke Previous myocardial infarction Angina pectoris Heart failure Aortic aneurysm Atrial fibrillation, prevention Atrial fibrillation, ventricular rate control ESRD/proteinuria Peripheral artery disease Other ISH (elderly) Metabolic syndrome Diabetes mellitus Pregnancy Blacks Drug ACE inhibitor, calcium antagonist, ARB Calcium antagonist, ACE inhibitor ACE inhibitor, ARB ACE inhibitor, ARB Any agent effectively lowering BP BB, ACE inhibitor, ARB BB, calcium antagonist Diuretic, BB, ACE inhibitor, ARB, mineralocorticoid receptor antagonist BB Consider ARB, ACE inhibitor, BB, or mineralocorticoid receptor antagonist BB, non-dihydropyridine calcium antagonist ACE inhibitor, ARB ACE inhibitor, calcium antagonist Diuretic, calcium antagonist ACE inhibitor, ARB, calcium antagonist ACE inhibitor, ARB Methyldopa, BB, calcium antagonist Diuretic, calcium antagonist Topic: Beta-blockers for prevention of progression if CVD in patients with AAA Recommendati on Basis of There is only low quality evidence that suggest no benefit of betarecommendati on For patients with unrepaired abdominal aortic aneurysm (AAA), there is no recommendation for or against the use of beta blockers to reduce the risk of cardiovascular disease progression blockers in reducing AAA expansion or all-cause morality. The evidence so of insufficient quality and applicability to draw any meaningfully conclusions effects mortality; harms not reported. The balance between desirable and

7 Key Findings Scientific Evidence Underlying ACC/AHA Guidelines (JAMA. 2009; 301: ) Among ACC/AHA GLs updated by Sept % (1330 to 1973) increase in recommendations occurred, the largest number being Class II Of 16 current GL with Level Of Evidence recommendations 11% (314/2711) are A 48% (1246/2711) are C Only 9% (245/2711) are Class I and Level Of Evidence A How the JNC Process Has Evolved Strictly evidence-based Focus only on randomized controlled trials assessing important health outcomes (no use of intermediate/surrogate measures) Every included study is rated for quality by two independent reviewers using standardized tools Evidence statements graded for quality using prespecified criteria Separate grading for recommendations Independent methodology team to ensure objectivity of the review Initial set of recommendations focused on 3 key questions

8 Expertise Represented on JNC 8 Panel Hypertension, primary care, cardiology, nephrology, clinical trials, research methodology, evidence-based medicine, epidemiology, guideline development and implementation, nutrition/lifestyle, nursing, pharmacology, systems of care, geriatrics, and informatics Panel also includes senior scientists from NHLBI and NIDDK with expertise in hypertension, clinical trials, translational research, nephrology, guideline development, and evidence-based methodology Literature Review and Assessment Process Systematic search of literature for the CQ Citations found using inclusion/exclusion criteria Papers screened and reviewed for inclusion Result: unbiased list of studies based on a priori criteria Quality of each included study rated Good, Fair, Poor NHLBI study rating instruments Controlled randomized intervention studies

9 Data Abstraction and Evidence Tables Information from individual studies Key data abstracted into a database Evidence table for each study/paper: subjects, sample size, intervention, comparison, results Evidence summaries by Critical Question Tables and text of major elements relevant to the CQ Graded evidence statements Multiple ESs for each CQ Graded recommendations based on the evidence Multiple ESs could result in a single recommendation 17 NHLBI Study Assessment Tool: Controlled Intervention Studies Criteria Yes No Other 1.Was the study described as randomized, a randomized trial, a randomized clinical trial, or an RCT? 5. Were the people assessing the outcomes blinded to the participants group assignments? 7. Was the overall drop-out rate from the study at its endpoint 20% or less than the number originally allocated to treatment? 14. Were all randomized participants analyzed in the group to which they were originally assigned (i.e., did they use an intention-to-treat analysis)? Quality Rating (Good, Fair, Poor) (see guidance) Rater #1 initials: Additional Comments (If POOR, please state why): Rater #2 initials:

10 Summary Table for Goal BP Question NHLBI Systematic Review and Guideline Development Process Topic Area Identified Evidence Summarized; Graded by Panel w/ Methodologists Recommendations Developed and Graded By Panel Resources Obtained; Expert Panel Established Studies Quality Rated; Evidence Tables Developed Draft Reports Written, Reviewed, Revised Critical Questions, Study Eligibility Criteria Identified Literature Searched; All Eligible Studies Identified Reports Disseminated & Implemented *The Blue portion is the Systematic Review

11 This 2014 HTN evidence-based guideline focuses on the panel s 3 highest ranked questions related to HTN management 1. In adults with HTN, does initiating antihypertensive pharmacologic therapy at specific BP thresholds improve health outcomes? 2. In adults with HTN, does treatment with antihypertensive pharmacologic therapy to a specified BP goal lead to improvements in health outcomes? 3. In adults with HTN, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes?

12 Question 1: Among adults with hypertension, does initiating antihypertensive pharmacological therapy at specific BP thresholds improve health outcomes? Articles Screened = 1496 Included = 44 Good = 8 Fair = 18 Poor = 18 Excluded = 1452 (Did not meet prespecified inclusion criteria) Total Abstracted = 26 Question 2: Among adults, does treatment with antihypertensive pharmacological therapy to a specified BP goal lead to improvements in health outcomes? Articles Screened = 1978 Good = 17 Included = 92 Fair = 39 Total Abstracted = 56 Poor = 36 Excluded = 1886 (Did not meet prespecified inclusion criteria)

13 Question 3: In adults with hypertension, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes? Articles Screened = 2662 Good = 15 Included = 101 Fair = 51 Total Abstracted = 66 Poor = 35 Excluded = 2561 (Did not meet prespecified inclusion criteria) Recommendation In the general adult population 60 years of age and older, initiate pharmacologic treatment to lower blood pressure at SBP 150mm Hg or DBP 90mm Hg and treat to a goal SBP <150 mm Hg and goal DBP <90mmHg. (Strong Recommendation Grade A)

14 Why is it important not to recommend intensifying medication to reduce BP below the level proven in clinical trials? Lower thresholds identify a much larger population as having HTN and presumably needing drug therapy (e.g. reducing definition of HTN from <140/90 to <120/80 doubles those with HTN Millions classified as HTN based on lower goals require more drugs Treating to lower BP goals may be harmful If neither beneficial or harmful, resources would be wasted and patient adherence would suffer Recommendation Corollary : In the general population 60 years of age and older, if pharmacologic treatment for high blood pressure results in a lower achieved SBP (for example, less than 140 mmhg) and treatment is well tolerated without adverse effects on health or quality of life, treatment does not need to be adjusted Expert opinion

15 Major Trials Testing SBP Goals in General Populations SHEP Syst-Eur HYVET JATOS VALISH Number 4,736 4,695 3,845 4,418 3,260 Entry SBP Goal SBP <148 <150 <150 <140 <140 Achieved SBP Stroke 36% 42% ns ns ns CVD 32% 31% 34% ns ns Mortality ns ns 21% ns SBP = systolic blood pressure ns CVD = cardiovascular disease Why Not Use Achieved Blood Pressures? Mean achieved BPs are not Goal BPs Post Hoc Analyses of patients achieving lower BPs tend to identify those at lower risk: less LVH, lower baseline BPs, fewer meds, improved med adherence

16 Cochrane Database of Systematic Reviews: Treatment Blood Pressure Targets for Hypertension 2009 The cohort of patients with low blood pressure as identified by achieved blood pressure selects for patients who did not have sustained elevated blood pressure in the first place, for patients in whom the blood pressure is most easily reduced, for patients with the lowest baseline blood pressure, and for patients who are most compliant (healthy user effect, Dormuth 2009). continued Cochrane 2009 continued All of these factors are most likely associated with a lower risk of having an adverse cardiovascular event. The approach is thus heavily biased for finding less cardiovascular events in the patients with lower blood pressure. Arguedas JA, Perez MI, Wright JM

17 The Secondary Prevention of Small Subcortical Strokes (SPS3) Study Blood-pressure Targets in Patients with Recent Lacunar Stroke: The SPS3 Randomized Trial SPS3 Study Group, Benavente OR,et al. Lancet. 2013(Aug 10);382: SPS3 Coordinating Center: University of British Columbia, Vancouver, Canada SPS3 Statistical Center: University of Alabama at Birmingham, US SPS3 is sponsored by National Institutes of Health - NINDS NINDS: U01 NS38529 SPS3 Design Randomized multicenter international trial. Lacunar strokes within 180 days (mean 62), verified by MRI. Randomized to 2 interventions in a factorial design: 1) Antiplatelet therapy (double blind): -aspirin 325 mg + placebo -aspirin 325 mg + clopidogrel 75 mg 2) Target levels of blood pressure control (open label): - higher mmhg systolic (mean 138 mm Hg) - lower <130 mmhg systolic (mean 127 mm Hg) Outcomes: -Primary: recurrent stroke. -Secondary: major vascular events, cognitive decline, death participants, mean follow up 3.7 years. NCT

18 SPS3 Efficacy Outcomes *Defined as: stroke, MI, vascular deaths. Case Scenario: J-Point? A 74 year old female on BP meds has a blood pressure of 152/50. Goal BP should be: A) Standing SBP less than 140 B) Standing SBP less than 150 C) Standing DBP no less than D) 152/50

19 Recommendation In the general adult population less than 60 years of age, initiate pharmacologic treatment to lower blood pressure at SBP 140 mm Hg and treat to a goal SBP <140 mm Hg. Expert Opinion Recommendation In the general adult population less than 60 years of age, initiate pharmacologic treatment to lower blood pressure at DBP 90 mm Hg and treat to a goal DBP < 90 mm Hg. For age 30-59, Strong Recommendation Grade A; For age 18-29, Expert Opinion

20 Recommendation In the adult population with diabetes, initiate pharmacologic treatment to lower blood pressure at SBP 140 mm Hg or DBP 90 mm Hg and treat to a goal SBP < 140 mm Hg and goal <90 mmhg. Expert Opinion RCTs Testing BP Goals In Hypertensive Diabetic Patients Trial n Duration (years) SBP goal, mmhg DBP goal, mmhg Mean BP, less intense, mmhg Mean BP, more intense, mmhg Outcome Risk Reduction SHEP <148 none 155/72 146/68 Syst-Eur <150 none 162/82 153/78 HOT 1,501 3 none <80 148/85 144/81 UKPDS 1, <150 <85 154/87 144/82 ABCD none <75 138/86 132/78 ACCORD 4, <120 none Stroke 22% (ns) CVD 34% CHD 56% Stroke 69% CVD 62% CVD 51% MI 50% Stroke 30% (ns) CV death 67% DM-related 34% deaths 32% Stroke 44% Microvasc 37% Renal (1º) nc Microvasc nc Death 49% CVD ns CVD (1º) 12% (ns) Stroke 41% Ferrannini, Cushman. Lancet 2012;380:

21 Adverse Events Intensive N (%) Standard N (%) P 77 (3.3) 30 (1.3) < Hypotension 17 (0.7) 1 (0.04) < Syncope 12 (0.5) 5 (0.2) 0.10 Bradycardia or Arrhythmia 12 (0.5) 3 (0.1) 0.02 Hyperkalemia 9 (0.4) 1 (0.04) 0.01 Renal Failure 5 (0.2) 1 (0.04) 0.12 egfr ever <30 ml/min/1.73m2 99 (4.2) 52 (2.2) <0.001 Any Dialysis or ESRD 59 (2.5) 58 (2.4) (44) 188 (40) 0.36 Serious AE Dizziness on Standing Symptom experienced over past 30 days from HRQL sample of N=969 participants assessed at 12, 36, and 48 months post-randomization

22 Recommendation In the adult population with non-diabetic CKD, initiate pharmacologic treatment to lower blood pressure at SBP 140 mm Hg or DBP 90 mm Hg and treat to a goal SBP < 140 mm Hg and goal DBP<90 mmhg. Expert Opinion Evidence Statement 15 Regarding Goal BP in CKD (CKD Subpopulation) In adults less than 70 years of age with chronic kidney disease, the evidence is insufficient to determine if there is a benefit in cardiovascular or cerebrovascular health outcomes, or mortality of treatment with antihypertensive drug therapy to a lower blood pressure goal compared to a goal of <140/90mm Hg.

23 Evidence Statement 16 Regarding Goal BP in CKD (CKD Subpopulation) In adults with hypertension and chronic kidney disease without diabetes, there is evidence of no benefit on the progression of kidney disease of treatment with antihypertensive drug therapy to a lower blood pressure goal compared to a goal of <140/90mm Hg. Vote: Agree with the statement (17/17); Evidence Quality: Moderate (16/17); Low (1/17) Evidence Statement 17 Regarding Goal BP in CKD (Proteinuria Subgroups) In adults with hypertension and proteinuria without diabetes, there is insufficient evidence to determine whether there is a benefit of treatment with antihypertensive drug therapy to a lower blood pressure goal compared to a goal of <140/90mm Hg on cardiovascular or cerebrovascular health outcomes or mortality. Vote: Agree with the statement (17/17); Evidence Quality: Unable to determine because there is insufficient evidence

24 Recommendation In the adult population age 18 to 80 years of age with chronic kidney disease and hypertension, initial antihypertensive treatment should include an ACE inhibitor or ARB to improve kidney outcomes. Moderate recommendation Grade B Recommendation In the general non-black population, including those with diabetes, age 18 and over for whom blood pressure medication is recommended, initial antihypertensive treatment with a single agent should be with a thiazide-type diuretic, CCB, ACEI or ARB. In the general black population, including those with diabetes, initial antihypertensive treatment with a thiazide-type diuretic or CCB is preferred.

25 Initial Combinations of Medications Diuretics β-blockers should be included in the regimen if there is a compelling indication for a β-blocker ACE inhibitors or ARBs* Calcium antagonists * Combining ACEI with ARB discouraged 2006 Meta-Analysis: Atenolol vs Other Treatments End Point Summary OR (95% CI) P Death 1.10 ( ) CV Death 1.13 ( ) MI 1.05 ( ) 0.19 Stroke 1.26 ( ) Elliott WJ. JACC. 2006;47 (Suppl):361A.

26 ALLHAT CHD Final Outcomes Results Doxazosin vs. Chlorthalidone Relative Risk and 95% Confidence Intervals 1.03 ( ) All-Cause Mortality Combined CHD Stroke Heart Failure 1.03 ( ) 1.07 ( ) 1.26 ( ) 1.80 ( ) Combined CVD, p< ( ) Favors Doxazosin Favors Chlorthalidone Hypertension 2003;42: ALLHAT Cumulative Percent Controlled (BP <140/90 mm Hg) at Five Years 66 Percent or 2 Any Number of Prescribed Drugs Derived from Cushman et al. J Clin Hypertens ;4:

27 Hypertension Treatment Algorithm Adult Hypertension ACE -Inhibitor 2 / Thiazide Diuretic Lisinopril / HCTZ (Advance as needed) 20 / 25 mg X _ daily 20 / 25 mg X 1 daily 20 / 25 mg X 2 daily Pregnancy Potential : Avoid ACE -Inhibitors 2 If ACE I intolerant or pregnancy potential Thiazide Diuretic Chlorthalidone 12.5 mg! 25 mg OR HCTZ 25 mg! 50 mg If not in control If not in control Calcium Channel Blocker Add amlodipine 5 mg X _ daily! 5 mg X 1 daily! 10 mg daily If not in control Beta -Blocker OR Spironolactone Add a tenol ol 25 mg daily! 50 mg daily (K eep heart rate > 55) OR IF on thiazide AND egfr! 60 ml/min AND K < 4.5 Add spironolactone 12.5 mg daily! 25 mg daily If not in control

28 Begin with Lisinopril/HCTZ Adult ACE -Inhibitor 2 / Thiazide Diuretic Lisinopril / HCTZ (Advance as needed) 20 / 25 mg X _ daily 20 / 25 mg X 1 daily 20 / 25 mg X 2 daily Pregnancy Potential : Avoid ACE -Inhibitors 2 If not in control Simple Algorithm: Fixed Dose Combination Based SIMPLICITY = PERFORMANCE Fewer steps Fewer pills Faster control Fewer visits/ improved access

29 Amlodipine is Third Drug If not in control Calcium Channel Blocker Add amlodipine 5 mg X _ daily! 5 mg X 1 daily! 10 mg daily If not in control Spironolactone Preferred Fourth Drug Spironolactone or Beta-Blocker IF on thiazide AND egfr! 60 ml/min AND K < 4.5 Add spironolactone 12.5 mg daily! 25 mg daily OR Add a tenolol 25 mg daily! 50 mg daily (K eep heart rate > 55) If not in control

30 Goal SBP < 150 mmhg for the General Population Recommendation 1 had the highest level of JNC 8 evidentiary support SHEP included 15% African American patients SHEP included patients with history of MI and stroke, 10% had diabetes Syst Eur included patients with history of MI and stroke HYVET included patients with MI, stroke, CKD, and HF 60

31 Ischemic Heart Disease Mortality Rate in Each Decade of Age IHD mortality (floating absolute risk and 95% CI) SBP DBP Age at risk: y y y y y Usual SBP (mm Hg) Usual DBP (mm Hg) IHD, ischemic heart disease. Prospective Studies Collaboration. Lancet ;360: Experimentation Trumps Observation JATOS and VALISH compared SBP goals <160 and <150 versus <140 in elderly patients ACCORD showed no difference comparing SBP goal < 140 versus <120 in patients with diabetes, except for more side effects with the lower goal SPS3 did not show a significant difference comparing goal SBP <150 versus <130 for the primary endpoint of recurrent stroke in patients with a personal history of stroke

32 Current NCQA proposal for Controlling High Blood Pressure Rate 1: Members years with most recent BP <140/90 Rate 2: Members 60 and older with most recent BP < 150/90 Rate 3: Total (Rate 1 + Rate 2) HEDIS 2015 performance metrics Common Blood Pressure Errors That Raise SBP 5-10 mmhg mmhg too high Cuff too small 5-10 Unsupported arm 5-10 Patient talking 10 Patient actively listening 5 Back unsupported 5-10 Feet not on floor 5-10 Legs crossed 5-10 Full bladder 10 Forearm blood pressure 5-10

33 Is the Hypertension Real? Mean difference between referring doctor BP and ABP (mmhg) in patients with resistant HTN Percent of patients with resistant HTN who had BP < 135/85 mmhg with ABP MA Brown, et al. Am J Hypertens SBP DBP % with controlled BP

34 ABP and CV Risk Dolan: Hypertension, Volume 46(1).July Cause of Resistance Cause of resistance found in 133/141 94% (83/91 91%) cases Psychological causes 9% Office resistance 6% Unknown 6% Nonadherence 16% Secondary HTN 5% Interfering substances 1% Drug-related causes 58% Primary cause of resistant hypertension Garg JP, et al. Am J Hypertens 2003;16:

35 70 Questions?

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