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JNC 8 H Y P E R T E N S I O N G U I D E L I N E STHE BLOOD PRESSURE LIMBOANDHOW LOW SHOULD YOU GO?HIGH LOW32nd Annual Advances in Heart DiseaseDecember 18, 2015Binh An P. Phan, MDAssociate Professor of MedicineDivision of CardiologySan Francisco General HospitalUniversity of California, San FranciscoDisclosures: noneQuestion #1A 55 yo white woman with a history of HTN and CADpresents to your clinic for the first time. Her bloodpressure is 157/95. You start her on HCTZ 25 mg qdand ask that she return in 1 week for a BP check.What is her BP goal?A)B)C)D)150/90140/90130/85120/801

Question #2An 84 yo man without a past medical history returns toyour clinic with a recurrent BP of 142/94, confirmed onseveral checks. He is not taking any medications.How many would start him on BP medication?A) YesB) NoQuestion #3A 66 yo black man with HTN presents to your office forthe first time. His BP is 174/99.Which of the following regimen is the least preferredoption to start?A)B)C)D)HCTZ 25 mg qdChlorthalidone 25 mg qdAmlodipine 10 mg qdLisinopril 20 mg qd2

Outline Review historical controversy in the treatment ofhypertension Discuss JNC 8 guidelines and the evidence used toconstruct recommendations Assess impact of recent clinical trial data on JNC 8 andhypertension managementHistorical controversy in treatment of hypertensionApril 12, 1945300/1903

Historical controversy in treatment of hypertension“The greatest danger to a man with high blood pressurelies in its discovery, because then some fool is certain totry to reduce it.”– J.H. Hay, British Med J, 1931“Hypertension may be an important compensatorymechanism which should not be tampered with, evenwere it certain that we could control it.”– Paul Dudley White, 1937“People with mild benign hypertension with levels up to210/110 need not be treated.”– Friedberg, Disease of the Heart, 1946Current health burden of hypertension 70 million Americans and more than 1 billion people worldwide have hypertension 7 million deaths per year attributed to HTN Uncontrolled HTN is the greatest contributor to stroke andischemic heart disease Number one reason listed for office visitsHajjar et al. JAMA 2003. World Health Report WHO 2002. Burt el al. Hypertension 1995.4

Age related changes in blood pressure150Blood pressure (mmHg)systolic125menwomen100diastolic7520304050Age (years)607080Burt el al. Hypertension 1995.Blood pressure predicts CV mortalityMeta-analysis of 61 population studies including 958,074 adults.Prospective Studies Collaboration. Lancet 2002.5

CV benefits of treating HTN from RCTsHeartfailureStrokeCVdeath- 10Riskreduction(%)20%- 20- 3040%- 4050%- 50Hebert et al. Archives Int Med 1993.2003 JNC 7 HTN treatment algorithmLifestyle modificationsGoal blood pressure 140/90 mmHg 130/80 mmHg with diabetes or CKDInitial drug choicesWithout compelling indicationsWith compelling indicationsStage 1 HTNSBP 140-159DBP 90-99Stage 2 HTNSBP 160DBP 100Drug(s) for compellingindicationsDiuretics;consider ACEi,ARB, BB, CCB2 drug combodiuretic, ACEi,ARB, BB,CCBDiuretics, ACE-I, ARB, BB,CCB as neededJNC 7. JAMA 2003.6

Evolution of classification of hypertensionSBP (mmHg)JNC 1, 2 (1977, 1980)JNC 3 (1984)DBP (mmHg) 105 16090-104 mild105-114 moderate 115 severeJNC 6 (1997)140-159 stage I160-179 stage II 180 stage III90-99 stage I100-109 stage II 109 stage IIIJNC 7 (2003)120-140 pre-HTN140-159 stage I 160 stage II90-99 stage I 100 stage IIJNC 8James et al. JAMA 2014.7

JNC 8 restricted to answering 3 questions Does starting drugs at specific BP thresholds improveoutcomes? Does titrating drugs to a specific BP goal improveoutcome? Do various BP drugs or drug classes differ in benefits andharms on specific outcome?9 evidence-based recommendationsJames et al. JAMA 2014.Strength of the 9 JNC 8 recommendationsGrade Strength of recommendationJNC 8AStrong Recommendation- high certainty that benefit is substantial2BModerate Recommendation- moderate certainty benefit is moderate to substantial or thereis high certainty that benefit is moderate2CWeak Recommendation- moderate certainty that there is a small benefit1DRecommendation against- No benefit or that risks/harms outweigh benefits0EExpert Opinion4NNo Recommendation for or against0James et al. JAMA 2014.8

Recommendation #1: patients 60 years oldGroupStartGoalLevel of evidence 60 years old 150/90 mmHg 150/90 mmHgStrong evidenceGrade AHYVET trial: benefit of target 150/90 in very elderly3,845 patients 80 years with SBP 160 mmHgIndapamide diuretic 1.5mg daily perindopril 2-4mg daily as neededPlaceboTarget blood pressure: 150/80Primary endpoint: fatal and non-fatal strokesBeckett et al. NEJM 20089

HYVET trial: benefit of HTN rx in the very elderlyOUTCOME: 34% CV events, 39% stroke death,21% total mortalityBeckett et al. NEJM 2008VALISH trial: no benefit of target 140/90 in elderly3,260 patients 70-84 years old with SBP 160 mmHgStrict ControlSBP 140 mmHgModerate ControlSBP 140-150 mmHgRx: Valsartan diuretic, CCB as neededNo difference in primary outcome of sudden death, CVA,MI, cardiac death, renal dysfunctionOgihara et al. Hypertension 2010.10

Recommendation #2, #3: patients 60 years oldGroupStartGoalLevel of evidence 60 years oldDBP 90 mmHg 90 mmHgStrong evidenceGrade A 60 years oldSBP 140 mmHg 140 mmHgExpert opinionGrade EJames et al. JAMA 2014.Recommendation #2, #3: patients 60 years oldPlaceboN 194Active RxN 186Stroke205Total coronary event1311Fatal coronary event116CHF110Renal damage30Deaths198Active rx: HCTZ 50 mg/reserpine 0.1 mg bid, hydralazine 35-50 mg tidVA Coop Study Group on Antihypertensive Agents. JAMA 1970.11

Recommendation #4, #5: patients with CKD or DMGroupStartGoalCKD or DM 140/90 mmHg 140/90 mmHgLevel ofevidenceExpert opinionGrade EJNC 7 recommended goal of 130/80 for adults with CKD or DMJames et al. JAMA 2014.MDRD trial: HTN rx in CKD1,585 patients with GFR 25-55Low blood pressureGoal MAP 92 (120/80)Usual blood pressureGoal MAP 107 (140/90)Rx: ACEi plus diuretic or CCB as neededOutcome: no difference in renal disease progression orcardiovascular mortalityKlahr et al. NEJM 199412

ACCORD Trial: HTN rx in DM4,773 patients with DMTarget SBP 120 mmHgTarget SBP 140 mmHgRx: all major classes of HTN therapiesMean SBP 119 mmHgMean SBP 133.5 mmHgNo difference in composite primary outcome: nonfatal MI,nonfatal stroke, or CV deathACCORD Study Group. NEJM 2010Recommendation #6: Rx in nonblack populationGroupRecommended treatmentLevel of evidenceGeneralnonblackpopulationThiazide-type diuretic, CCB,ACEi, ARBModeraterecommendationGrade BJames et al. JAMA 2014.13

ALLHAT: Comparison of HTN regimens33,357 patients with HTN and 1 other CVD risk factorschlorthalidone12.5 to 25 mg/damlodipine2.5 to 10 mg/dlisinopril10 to 40 mg/dGoal BP 140/90No difference in primary outcome combined fatal CHD ornonfatal MIALLHAT Study Group. JAMA 2002.Recommendation #7: Rx in black populationGroupRecommended treatmentLevel of evidenceBlackpopulationThiazide-type diuretic or CCBModeraterecommendationGrade BJames et al. JAMA 2014.14

ALLHAT: Increased risk of stroke and combined CVDevents in Black subjects taking lisinopril**Amlodipine or lisinopril treatment compared to chlorthalidone.Wright et al. JAMA 2005Recommendation #8: Rx in CKDGroupRecommended treatmentLevel of evidenceCKDACEi, ARBModeraterecommendationGrade BApplies to all CKD patients regardless of race or DM statusJames et al. JAMA 2014.15

Recommendation #8: Rx in CKDStudyPtsDesignRR CKDprogressionMaschio et al. ndpoint: Nonfatal MI, stroke, or HF, and CV deathSPRINT Research Group. NEJM 201521

SPRINT trial: benefit with more aggressive BP goalMean SBP 134.6 mmHgMean SBP 121.5 mmHgSPRINT Research Group. NEJM 2015SPRINT trial: benefit with more aggressive BP goal 25% Primary outcome:MI, ACS, CVA, HF, CV deathNNT 61 27% all cause mortalityNNT 90SPRINT Research Group. NEJM 201522

SPRINT trial: benefit with more aggressive BP goalSPRINT Research Group. NEJM 2015My take home points on HTN management Consider BP goal of 140/90 for all adults, including those 60years old In those adults with increased CVD risk or advanced CKD,consider lower BP goal Thiazide diuretics, ACE-i/ARB, and CCB are equally effective inlowering BP and reducing CV risk in the general non-blackpopulation Tailor HTN treatment based upon proven therapies for specificcomorbidities23

Thank you.24

JNC 1, 2 (1977, 1980) 105 JNC 3 (1984) 160 90-104 mild 105-114 moderate 115 severe JNC 6 (1997) 140-159 stage I 160-179 stage II 180 stage III 90-99 stage I 100-109 stage II 109 stage III JNC 7 (2003) 120-140 pre-HTN 140-159 stage I 160 stage II 90-99 stage I 10

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