JNC8 Guidelines for Management of Hypertension

Towards an Evidence Based Towards an Evidence Based Treatment Strategy in HypertensionTreatment Strategy in Hypertension

Tony Woolley M.D.Tony Woolley M.D.

Park Nicollet ClinicPark Nicollet Clinic

Clinical Associate Professor of Clinical Associate Professor of Medicine, University of MinnesotaMedicine, University of Minnesota

[email protected]@parknicollet.com

My First Lesson In HypertensionMy First Lesson In Hypertension

CIRCA 1980, first Internal Med clinical rotation

Begin Treatment if BP>140/90

Start thiazide diuretic, 50mg qd


•What should our goal BP be, especially for What should our goal BP be, especially for special populations ( Diabetes, Renal disease, special populations ( Diabetes, Renal disease, Coronary disease, other high risk populations)?Coronary disease, other high risk populations)?

•What medication strategies are best supported What medication strategies are best supported by evidence, especially for special populations?by evidence, especially for special populations?

•How does the gap between clinical practice and How does the gap between clinical practice and clinical evidence grow? ( Analysis of Bias)clinical evidence grow? ( Analysis of Bias)

Evidence Based PracticeEvidence Based PracticeMajor PrinciplesMajor Principles

• Hierarchy of EvidenceHierarchy of Evidence– Level 1 evidence= Systematic Reviews or Level 1 evidence= Systematic Reviews or

Meta-analysis of RCTs or Single high quality Meta-analysis of RCTs or Single high quality RCTs (like ALLHAT or ACCORD)RCTs (like ALLHAT or ACCORD)

• Tempered by Tempered by

–Clinical JudgmentClinical Judgment and and–Patient PreferencesPatient Preferences

Evidence HierarchyEvidence Hierarchy

More of This

And less of This


•What should our goal BP be, especially for What should our goal BP be, especially for special populations ( Diabetes, Renal disease, special populations ( Diabetes, Renal disease, Coronary disease, other high risk populations)?Coronary disease, other high risk populations)?

Current Recommendations for BP Current Recommendations for BP GoalsGoals

• JNC 7 (JNC 7 (Joint National Committee on Prevention, Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood) Detection, Evaluation, and Treatment of High Blood) PressurePressure

– Goal BP <140/90 Goal BP <140/90

– Goal with Diabetes or CKD <130/80Goal with Diabetes or CKD <130/80

• JNC 8 Expected Mid 2011JNC 8 Expected Mid 2011

Hypertension. 2003;42:1206

Current Recommendations for BP Current Recommendations for BP GoalsGoals

• JNC VII <140/90, in Diabetes or CKD <130/80JNC VII <140/90, in Diabetes or CKD <130/80• AHA/ACC 2007 <130/80 “high risk”;CVD, CKD, DM AHA/ACC 2007 <130/80 “high risk”;CVD, CKD, DM

or Framingham 10 yr risk score >10%or Framingham 10 yr risk score >10%• ADA DM <130/80 ADA DM <130/80 • WHO/ISH <140/90, in DM, CVD or CKD <130/80 WHO/ISH <140/90, in DM, CVD or CKD <130/80

“seems appropriate”“seems appropriate”• N/DOQI 2004 CKD <130/80N/DOQI 2004 CKD <130/80• BHS <140/90, <130/80 DM,CVD or CKD BHS <140/90, <130/80 DM,CVD or CKD • ESH-ESC “at least” <130/80 DM, CVD or CKD ESH-ESC “at least” <130/80 DM, CVD or CKD

Hypertension in DiabetesHypertension in Diabetes

• Guidelines say: Treat to <130/80Guidelines say: Treat to <130/80

• ADA Recommends ACE/ARB firstADA Recommends ACE/ARB first

Action to Control Cardiovascular Action to Control Cardiovascular Risk in Diabetes (ACCORD) TrialRisk in Diabetes (ACCORD) Trial

• NHLBI 10,251 Type 2 diabeticsNHLBI 10,251 Type 2 diabetics

• Three Trial armsThree Trial arms– Glycemic controlGlycemic control– BP <120BP <120– Lipids: Fibrate added to StatinLipids: Fibrate added to Statin

• BP arm 4,773 randomized to SBP<120 or BP arm 4,773 randomized to SBP<120 or <140<140

www.nejm.org March 14, 2010

Average after 1st year: 133.5 Standard vs. 119.3 Intensive, Delta = 14.2

Mean # Meds Intensive: 3.2 3.4 3.5 3.4 Standard: 1.9 2.1 2.2 2.3

Intensive Events (%/yr)

StandardEvents (%/yr) RR (95% CI) P

Primary 208 (1.87) 237 (2.09) 0.88 (0.73-1.06) 0.20

Total Mortality 150 (1.28) 144 (1.19) 1.07 (0.85-1.35) 0.55

Cardiovascular Deaths

60 (0.52) 58 (0.49) 1.06 (0.74-1.52) 0.74

Nonfatal MI 126 (1.13) 146 (1.28) 0.87 (0.68-1.10) 0.25

Nonfatal Stroke 34 (0.30) 55 (0.47) 0.63 (0.41-0.96) 0.03

Total Stroke 36 (0.32) 62 (0.53) 0.59 (0.39-0.89) 0.01

Also examined Fatal/Nonfatal HF (HR=0.94, p=0.67), a composite of fatal coronary events, nonfatal MI and unstable angina (HR=0.94, p=0.50) and a composite of the primary outcome, revascularization and unstable angina (HR=0.95, p=0.40)

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Primary Outcome Nonfatal MI, Nonfatal Stroke or CVD Death Total Stroke

HR = 0.8895% CI (0.73-1.06)

HR = 0.5995% CI (0.39-0.89)

NNT for 5 years = 89

IntensiveIntensiveN (%)N (%)

StandardStandardN (%)N (%) PP

Serious AESerious AE 77 (3.3)77 (3.3) 30 (1.3)30 (1.3) <0.0001<0.0001

HypotensionHypotension 17 (0.7)17 (0.7) 1 (0.04)1 (0.04) <0.0001<0.0001

SyncopeSyncope 12 (0.5)12 (0.5) 5 (0.2)5 (0.2) 0.100.10Bradycardia or Bradycardia or ArrhythmiaArrhythmia 12 (0.5)12 (0.5) 3 (0.1)3 (0.1) 0.020.02

HyperkalemiaHyperkalemia 9 (0.4)9 (0.4) 1 (0.04)1 (0.04) 0.010.01

Renal FailureRenal Failure 5 (0.2)5 (0.2) 1 (0.04)1 (0.04) 0.120.12eGFR ever <30 eGFR ever <30 mL/min/1.73mmL/min/1.73m22 99 (4.2)99 (4.2) 52 (2.2)52 (2.2) <0.001<0.001

Any Dialysis or ESRDAny Dialysis or ESRD 59 (2.5)59 (2.5) 58 (2.4)58 (2.4) 0.930.93

Dizziness on StandingDizziness on Standing†† 217 (44)217 (44) 188 (40)188 (40) 0.360.36† Symptom experienced over past 30 days from HRQL sample of

N=969 participants assessed at 12, 36, and 48 months post-randomization

• The ACCORD BP trial evaluated the The ACCORD BP trial evaluated the effect of targeting a SBP goal of 120 mm effect of targeting a SBP goal of 120 mm Hg, compared to a goal of 140 mm Hg, in Hg, compared to a goal of 140 mm Hg, in patients with type 2 diabetes patients with type 2 diabetes

• The results provide no conclusive The results provide no conclusive evidence that the intensive BP control evidence that the intensive BP control strategy reduces the rate of a composite strategy reduces the rate of a composite of major CVD events in such patients.of major CVD events in such patients.

INVEST StudyINVEST Study

International Verapamil-Trandolapril StudyInternational Verapamil-Trandolapril Study

•Diabetic Subgroup 6400, all with CADDiabetic Subgroup 6400, all with CAD

•Achieved SBP <130, 130-139, 140+Achieved SBP <130, 130-139, 140+

OUTCOME

%

TIGHT CONTROL

USUAL CONTROL

UNCONTROLLED

Death, MI, Stroke

12.7 12.6 19.8 * CI 1.01-1.31

Mortality11.0 10.2 15.4

JAMA July 7,2010;304(1)61-68

Hypertension in DiabetesHypertension in Diabetes


• Evidence says: No renal or cardiovascular Evidence says: No renal or cardiovascular benefit with lower BP benefit with lower BP

• ACE/ARB therapy do improve renal ACE/ARB therapy do improve renal outcomes in patients with proteinuria outcomes in patients with proteinuria including microalbuminuriaincluding microalbuminuria

• New ICSI guideline: <140/85 (consider New ICSI guideline: <140/85 (consider <130/80 in patients with proteinuria)<130/80 in patients with proteinuria)

Hypertension in Coronary Artery Hypertension in Coronary Artery Disease and “High Risk” GroupsDisease and “High Risk” Groups

• AHA/ACC Guidelines say: Treat to AHA/ACC Guidelines say: Treat to <130/80<130/80

• High risk includes any vascular disease, High risk includes any vascular disease, Framingham risk score >10%Framingham risk score >10%

• Evidence Level 5 (Expert Opinion)Evidence Level 5 (Expert Opinion)

Framingham Risk Calculation, ExFramingham Risk Calculation, Ex..Age: 65

Gender: male

Total Cholesterol: 200 mg/dL

HDL Cholesterol: 40 mg/dL

Smoker: No

Systolic Blood Pressure: 140 mm/Hg

On medication for HBP: Yes

Risk Score* 19% * The risk score shown was derived on the basis of an equation. Other NCEP materials, such as ATP III print products, use a point-based system to calculate a risk score that approximates the equation-based one. ATP III Executive Summary and ATP III At-a-Glance.


• No Intent to Treat RCT addresses thisNo Intent to Treat RCT addresses this

• Lower Achieved BP has been associated Lower Achieved BP has been associated with no benefit or with no benefit or worsenedworsened outcomes in post outcomes in post hoc analysis of trials hoc analysis of trials – INVESTINVEST DM and CAD DM and CAD– ONTARGETONTARGET Vascular disease or DM Vascular disease or DM NEJM NEJM 358:1547-1559358:1547-1559

– I-PRESERVE I-PRESERVE Diastolic CHFDiastolic CHF

JAMA July 7,2010;304(1)61-68, NEJM 358:1547-1559

N Engl J Med 2008;359:2456–67


• AHA/ACC Guidelines say: Treat to AHA/ACC Guidelines say: Treat to <130/80<130/80

• High risk includes any vascular disease, High risk includes any vascular disease, Framingham risk score >10%Framingham risk score >10%

• Evidence says: No renal or cardiovascular Evidence says: No renal or cardiovascular benefit demonstrated in this overall groupbenefit demonstrated in this overall group

• 2010 ICSI guideline: <140/90 2010 ICSI guideline: <140/90

Hypertension in the ElderlyHypertension in the Elderly

JNC7 and other Guidelines say: JNC7 and other Guidelines say:

Treat to <140/90Treat to <140/90

High Risk Conditions:High Risk Conditions:

Treat to <130/80Treat to <130/80

Hypertension in the ElderlyHypertension in the ElderlyMeta-analysis RCTs in Patients ≥60 yearsMeta-analysis RCTs in Patients ≥60 years

15 trials n=24,05515 trials n=24,055Frail elderly excluded from trialsFrail elderly excluded from trialsResults similar for isolated systolic and BP Results similar for isolated systolic and BP

trialstrialsNo trials have recruited patients with No trials have recruited patients with

Isolated Systolic Hypertension and SBP<160Isolated Systolic Hypertension and SBP<160Total CV Morbidity reduced RR .68, ARR 4.3% NNT Total CV Morbidity reduced RR .68, ARR 4.3% NNT 2323Total Mortality reduced RR .90 ARR 1.2%Total Mortality reduced RR .90 ARR 1.2%Citation: Musini VM, Tejani AM, Bassett K, Wright JM. Pharmacotherapy for hypertension in the elderly. Citation: Musini VM, Tejani AM, Bassett K, Wright JM. Pharmacotherapy for hypertension in the elderly. Cochrane Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD000028. DOI: 10.1002/14651858.CD000028.pub2.Database of Systematic Reviews 2009, Issue 4. Art. No.: CD000028. DOI: 10.1002/14651858.CD000028.pub2.

Issues in Treatment of the Very Issues in Treatment of the Very Elderly (>80)Elderly (>80)

• Epidemiologic population studies Epidemiologic population studies show better survival with higher BPshow better survival with higher BP

• STOP-2 Worse survival in treated STOP-2 Worse survival in treated hypertensives with SBP<140hypertensives with SBP<140

Oates et al.Journal of the American Geriatrics Society Volume 55, Issue 3, pages 383–388, March 2007

Hypertension in the ElderlyHypertension in the ElderlyMetaanalysis RCTs in Patients ≥80 yearsMetaanalysis RCTs in Patients ≥80 years

9 trials n=6,7989 trials n=6,798

Frail elderly excluded Frail elderly excluded from trialsfrom trials

Achieved SBP 143-148Achieved SBP 143-148

Stroke benefit: Stroke benefit: RR .67 ARR RR .67 ARR 4% NNT 254% NNT 25

Total Mortality: No benefit Total Mortality: No benefit RR RR .97.97

Citation: Musini VM, Tejani AM, Bassett K, Wright JM. Citation: Musini VM, Tejani AM, Bassett K, Wright JM. Pharmacotherapy for hypertension in the elderly. Pharmacotherapy for hypertension in the elderly. Cochrane Database of Systematic Reviews 2009, Issue Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD000028. DOI: 4. Art. No.: CD000028. DOI: 10.1002/14651858.CD000028.pub2.10.1002/14651858.CD000028.pub2.

HYVETHYVET

• Only HTN RCT in Patients ≥80 Only HTN RCT in Patients ≥80 yearsyears

• N=3850 mean age 83 mean SBP 173N=3850 mean age 83 mean SBP 173

• Goal SBP<150, mean achieved SBP Goal SBP<150, mean achieved SBP =143=143

• Placebo vs perendipril/indapamidePlacebo vs perendipril/indapamide

• 18 month BP separation -15/6 mmHg18 month BP separation -15/6 mmHg

HYVET ResultsHYVET Results

Hypertension in the ElderlyHypertension in the Elderly

•JNC7 and other Guidelines say: JNC7 and other Guidelines say: • Treat to <140/90Treat to <140/90• High Risk Conditions:High Risk Conditions: Treat to <130/80Treat to <130/80

•Evidence Suggests:Evidence Suggests:• Initiate Treatment at 160 with SBP goal Initiate Treatment at 160 with SBP goal

Hypertension in CKDHypertension in CKD


• ACE or ARB preferred in patients with ACE or ARB preferred in patients with proteinuriaproteinuria


• Relevant clinical trialsRelevant clinical trials– MDRD 1994 N=884 pt with GFR 13-55MDRD 1994 N=884 pt with GFR 13-55– RCT MAP< 93 vs < 107 (<125/75 vs <140/90)RCT MAP< 93 vs < 107 (<125/75 vs <140/90)– Overall result No benefit in CV or renal Overall result No benefit in CV or renal

outcomesoutcomes– Post hoc Subgroup analysis; 54 pts with Post hoc Subgroup analysis; 54 pts with

>3g/24h proteinuria had renal outcome benefit>3g/24h proteinuria had renal outcome benefit


• Relevant clinical trials: AASK 2002Relevant clinical trials: AASK 2002– RCT 1094 African American patients with RCT 1094 African American patients with

hypertensive nephropathy assigned to hypertensive nephropathy assigned to MAP<93 vs 102-107MAP<93 vs 102-107

– Achieved BP 130/78 vs 141/86Achieved BP 130/78 vs 141/86– 4 year result no benefit4 year result no benefit– 10 year Cohort followup: No benefit overall10 year Cohort followup: No benefit overall– Protenuric subgroup 27% reduction in Protenuric subgroup 27% reduction in

doubling of GFR at 10 yearsdoubling of GFR at 10 years



• Evidence says: No renal or cardiovascular Evidence says: No renal or cardiovascular benefit in this overall groupbenefit in this overall group

• Long term renal benefit in patients with Long term renal benefit in patients with proteinuria (>300mg/dl)proteinuria (>300mg/dl)

• New ICSI guideline: <140/90, consider New ICSI guideline: <140/90, consider <130/80 in patients with proteinuria<130/80 in patients with proteinuria

Evidence Based GoalsEvidence Based Goals

• <140/90 for almost everybody<140/90 for almost everybody• Perhaps <130/80 in patients with Perhaps <130/80 in patients with

proteinuricproteinuric renal disease at risk for ESRD renal disease at risk for ESRD• Perhaps a bit higher (<150 systolic) in Perhaps a bit higher (<150 systolic) in

older patients with isolated systolic HTNolder patients with isolated systolic HTN

The gap between what we know and The gap between what we know and what we think we know or…what we think we know or…

How Do We Get It so Wrong?How Do We Get It so Wrong?

•Theraputic Optimism•The bias that the benefit of treatment exceeds the risk/harm

•Authority Bias•Overvaluing the opinions of experts

•Influence of Industry•More treatment/diagnosis is usually good for business, and sponsorship of research and education tends to support more rather than less treatment

The gap between what we know and The gap between what we know and what we think we know what we think we know

•Confirmation Bias•We are much more likely to seek information that confirms rather than refutes what we believe to be true

•Forgetting the asymmetry of epidemiology and treatment

•In many (?most) instances, correcting a causal risk factor does not fully resolve associated risk

Evidence HierarchyEvidence Hierarchy

More of This

And less of This

My Latest Lesson In My Latest Lesson In HypertensionHypertension

CIRCA 2010

Begin Treatment if BP>140/90

Start thiazide , Break it in half

Selected References

ICSI Hypertension Guideline 2010 revision http://www.icsi.org/guidelines_and_more/...

Treatment Blood Pressure Targets for Hypertension: Cochrane Review 2009

http://onlinelibrary.wiley.com/o/cochrane/clsysrev/articles/CD004349/frame.html

ACCORD BP Study, March 14 2010

The Effects of Intensive Blood Pressire Control in Type 2 Diabetes Mellitus

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1001286

INVEST Diabetes Subgroup

Tight Blood Pressure Control and Cardiovascular Outcomes Among Hypertensive Patients with Diabetes and Coronary Artery Disease

JAMA, Vol 304, 1, 61-67

Selected References

Hypertension in the Very Elderly Trial (HYVET) 2008

N Engl J Med 2008; 358(18):1887-98.

Pharmacotherapy of Hypertension in the Elderly: Cochrane Review 2010


AASK 10 year follow up 2010

Intensive Blood-Pressure Control in Hypertensive Chronic Kidney Disease

N Engl J Med 2010; 363:918-929

First Line Drugs for Hypertension: Cochrane Review 2009


Additional Slides, Treatment

• These will not be discussed in the presentation

Drug Rx for HTNDrug Rx for HTN

Where is the evidence Where is the evidence pointing us?pointing us?

Drug Rx for HTNDrug Rx for HTN• JNC 7JNC 7

– Thiazides for mostThiazides for most– Other First line drugsOther First line drugs

• ACE/ARBACE/ARB• Beta BlockersBeta Blockers• CCBCCB

Cochrane Review, Drugs for HTNCochrane Review, Drugs for HTN

• 57 trials, n=58,04057 trials, n=58,040

• Conclusion: Low dose thiazides reduce all Conclusion: Low dose thiazides reduce all morbidity and mortality outcomes. ACEI morbidity and mortality outcomes. ACEI and Calcium blockers may be similarly and Calcium blockers may be similarly effective but the evidence is less robust. effective but the evidence is less robust.

• Beta blockers and high dose thiazides are Beta blockers and high dose thiazides are inferior to low dose thiazidesinferior to low dose thiazides

Cochrane Review, Drugs for HTNCochrane Review, Drugs for HTN

#RCT Mortality Stroke CHD CV events

Thiazides 19 .89 .63 .84 .70

low dose 8 .72

high dose 11 1.01 ns

β Blocker 5 .96 ns .83 .90 ns .89

ACEI 3 .83 .65 .81 .76

CCB 1 .86 ns .58 .77 ns .71

The Cochrane Library 2009, issue 3. http//www.thecochranelibrary.com

Years to CHD Event0 1 2 3 4 5 6 7

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Number at Risk: Chlorthalidone 15,255 14,477 13,820 13,102 11,362 6,340 2,956 209 Amlodipine 9,048 8,576 8,218 7,843 6,824 3,870 1,878 215 Lisinopril 9,054 8,535 8,123 7,711 6,662 3,832 1,770 195

Cumulative Event Rates for the Primary Outcome (Fatal CHD or Nonfatal MI) by ALLHAT Treatment Group

RR (95% CI) p value

A/C 0.98 (0.90-1.07) 0.65

L/C 0.99 (0.91-1.08) 0.81

ALLHAT

ChlorthalidoneAmlodipineLisinopril

Nonfatal MI + CHD Death – Subgroup Comparisons – RR (95% CI)

Amlodipine Better Chlorthalidone Better

0.50 1 2

Non-Diabetic 0.97 (0.86, 1.09)

Diabetic 0.99 (0.87, 1.13)

Non-Black 0.97 (0.87, 1.08)

Black 1.01 (0.86, 1.18)

Women 0.99 (0.85, 1.15)

Men 0.98 (0.87, 1.09)

Age>=65 0.97 (0.88, 1.08)

Age <65 0.99 (0.85, 1.16)

Total 0.98 (0.90, 1.07)

Lisinopril Better Chlorthalidone Better

0.50 1 2

Non-Diabetic 0.99 (0.88, 1.11)

Diabetic 1.00 (0.87, 1.14)

Non-Black 0.94 (0.85, 1.05)

Black 1.10 (0.94, 1.28)

Women 1.06 (0.92, 1.23)

Men 0.94 (0.85, 1.05)

Age >= 65 1.01 (0.91, 1.12)

Age < 65 0.95 (0.81, 1.12)

Total 0.99 (0.91, 1.08)

ALLHAT

Beta blockers: What Happened to Beta blockers: What Happened to My Atenolol?My Atenolol?

• Meta-analysis of trials comparing beta Meta-analysis of trials comparing beta blockers with other antihypertensivesblockers with other antihypertensives

Outcome Outcome RR w/beta blockersRR w/beta blockers 95% CI95% CI •

Stroke Stroke 1.161.16 1.04-1.301.04-1.30•

MIMI 1.0201.020 .93-1.12.93-1.12•

All-cause mort.All-cause mort. 1.0301.030 .99-1.08.99-1.08

Lindholm LH, Carlberg B, and Samuelsson O. Should blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005; 366(9496):1545-1553

Atenolol vs other antihypertensives

Outcome Relative risk with atenolol 95% CI

Stroke 1.26 1.15-1.38

MI 1.05 0.91-1.21

All-cause mortality

1.08 1.02-1.14

Lindholm LH, Carlberg B, and Samuelsson O. Should blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005; 366(9496):1545-1553

Beta Blockers Are Now 3Beta Blockers Are Now 3rdrd Line Line TherapyTherapy

• AfterAfter diuretic, ACE/ARB, CCB… diuretic, ACE/ARB, CCB…• Benefit in clinical trials demonstrated Benefit in clinical trials demonstrated

mainly in combination therapymainly in combination therapy• Appear less effective than other classes at Appear less effective than other classes at

preventing strokepreventing stroke• Are less effective in older patientsAre less effective in older patients• Monotherapy mainly in patients with Monotherapy mainly in patients with

compelling indications (like angina, post-compelling indications (like angina, post-MI, tachyarrhythmias…)MI, tachyarrhythmias…)

The Big 3 ConceptThe Big 3 Concept

• Thiazides, ACEI and CCBs Thiazides, ACEI and CCBs

• All appear about equally effectiveAll appear about equally effective

• Work well togetherWork well together

Diuretics in HTNDiuretics in HTN

• Thiazides are most effective; optimal dose Thiazides are most effective; optimal dose 6.25-25mg6.25-25mg

• Metolazone can be used if Cr CL<30Metolazone can be used if Cr CL<30

• Spironolactone works well for many who Spironolactone works well for many who don’t tolerate thiazidedon’t tolerate thiazide

• Loop diuretics (except torsemide) need to Loop diuretics (except torsemide) need to be given twice a daybe given twice a day

ACE Inhibitors/ARBs: Special ACE Inhibitors/ARBs: Special RolesRoles

• In a broad range of patients ACE/ARBs appear In a broad range of patients ACE/ARBs appear to contribute to improved endpoints beyond to contribute to improved endpoints beyond antihypertensive effectsantihypertensive effects– LV Systolic Dysfunction (CHF)LV Systolic Dysfunction (CHF)– Diabetes with microalbuminuriaDiabetes with microalbuminuria– Proteinuric renalProteinuric renal– ? Post MI? Post MI

• NotNot in diastolic CHF, diabetes without proteinuria in diastolic CHF, diabetes without proteinuria or non-proteinuric renal disease. or non-proteinuric renal disease.

ACEI/ARBs: One or the other, not bothACEI/ARBs: One or the other, not bothThe ONTARGET StudyThe ONTARGET Study

– RCCT N=17,118 high risk patients with DM or RCCT N=17,118 high risk patients with DM or vascular disease vascular disease

– Ramipril, Telmisartan or both for 56 monthsRamipril, Telmisartan or both for 56 months– No additional benefit in combined vascular No additional benefit in combined vascular

eventsevents– Combination therapy caused higher rate of Combination therapy caused higher rate of

adverse events (adverse events (hypotensive symptoms (4.8% vs. hypotensive symptoms (4.8% vs. 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P=0.03), 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P=0.03), and renal dysfunction (13.5% vs. 10.2%, P<0.001) and renal dysfunction (13.5% vs. 10.2%, P<0.001)

• Similar findings in CHF trials Similar findings in CHF trials NEJMVolume 358:1547-1559, April 10, 2008

Dihydropyridine CCBs: The Swiss Dihydropyridine CCBs: The Swiss Army Knife of BP medsArmy Knife of BP meds

• No contraindicating medical conditions (CHF, No contraindicating medical conditions (CHF, diabetes, CKD, arrhythmias etc)diabetes, CKD, arrhythmias etc)

• Effective in all age and ethnicity groupsEffective in all age and ethnicity groups• Good dose response curveGood dose response curve• Can be used with any other drug class, including Can be used with any other drug class, including

non-dihydropyridine CCBsnon-dihydropyridine CCBs

Dihydropyridine CCBs: Dihydropyridine CCBs: Clinical TrialsClinical Trials

• Equivalent to Thiazide and ACE in ALLHAT Equivalent to Thiazide and ACE in ALLHAT (including 15,297 diabetics) (including 15,297 diabetics)

• Outperformed thiazide in combination with ACE Outperformed thiazide in combination with ACE (ACCOMPLISH)(ACCOMPLISH)

• Superior to ACE in African Americans (ALLHAT)Superior to ACE in African Americans (ALLHAT)• Superior to ACE in pts with CAD (CAMELOT)Superior to ACE in pts with CAD (CAMELOT)• Highly effective in elderly isolated systolic HTN, Highly effective in elderly isolated systolic HTN,

including 76% reduction in CV mortality in including 76% reduction in CV mortality in diabetic subgroup (Syst-Eur)diabetic subgroup (Syst-Eur)

JAMA. 2004;292(18):2217-2222 NEJM 2008 359:2417-2428

JAMA. 2002;288:2981-2997 NEJM. 1999;340:677-684

Dihydropyridine CCBs: The Swiss Dihydropyridine CCBs: The Swiss Army Knife of BP medsArmy Knife of BP meds

• Amlodipine 2.5-20 mg qd• Felodipine 2.5-20 mg qd• Isradipine 5-20 mg qd• Nicardipine SR 30-120 mg qd• Nifedipine ER 30-120 mg qd• Nisoldipine 20-60 mg qd

A Modest Proposal:A Modest Proposal:3 Drug Step-Care in Most Patients3 Drug Step-Care in Most Patients

• Thiazides, ACEI and CCBs work well Thiazides, ACEI and CCBs work well togethertogether

• Clinical Trials utilizing medication titration Clinical Trials utilizing medication titration by algorithm routinely achieve superior by algorithm routinely achieve superior control ratescontrol rates

• Combination therapy is needed for most Combination therapy is needed for most patients patients

Multidrug Therapy Needed Multidrug Therapy Needed to Achieve Target Blood Pressureto Achieve Target Blood Pressure

A Modest Proposal:A Modest Proposal:3 Drug Step-Care in Most Patients3 Drug Step-Care in Most Patients

• Step Care example: Step Care example: • Step IStep I Start Thiazide 12.5 mg; Start Start Thiazide 12.5 mg; Start

Lisinopril/HCT 20/12.5 if >160Lisinopril/HCT 20/12.5 if >160• Step 2Step 2 If close to goal increase thiazide If close to goal increase thiazide

to 25mg (Lisinipril 20/25) to 25mg (Lisinipril 20/25) Otherwise add second drug Otherwise add second drug

(Lisinopril 20mg, amlodipine 2.5-5mg)(Lisinopril 20mg, amlodipine 2.5-5mg)

• Step 3Step 3 Add 3Add 3rdrd drug drug• Step 4 Step 4 Titrate Amlodipine to 10-20 mgTitrate Amlodipine to 10-20 mg

Big 3 Add-onsBig 3 Add-ons

• Spironolactone 25 mg Spironolactone 25 mg – ““Aldactazide 25/25” if already on HCTZAldactazide 25/25” if already on HCTZ

– Monitor K+, especially with ACE/ARBMonitor K+, especially with ACE/ARB• Beta BlockersBeta Blockers

– ?Advantage of vasodilating drugs like ?Advantage of vasodilating drugs like labetalol, carvedilol, nebivolollabetalol, carvedilol, nebivolol

• Central agentsCentral agents– Ex Guanfacine 1-4 mg qhs. Easier to use than Ex Guanfacine 1-4 mg qhs. Easier to use than

clonidineclonidine

• Dose Titration (vs adding additional Dose Titration (vs adding additional medication)medication)

Treating to Goal- More Drugs to Treating to Goal- More Drugs to ConsiderConsider

• Example additionsExample additions– Doxazosin 2-10 mg qhsDoxazosin 2-10 mg qhs– Guanfacine 1-4 mg qhsGuanfacine 1-4 mg qhs– MinoxidilMinoxidil– Reserpine 0.05-.25mg qhsReserpine 0.05-.25mg qhs– Diltiazem or Verapamil 120-480 qd)Diltiazem or Verapamil 120-480 qd)– Direct renin inhibitor (Aliskerin)Direct renin inhibitor (Aliskerin)

Newer DrugsNewer Drugs

• Aliskerin (Tekturna)Aliskerin (Tekturna)– Direct Renin Inhibitor, ACEI likeDirect Renin Inhibitor, ACEI like

• Nebivolol (Bystolic)Nebivolol (Bystolic)– Vasodilating Beta BlockerVasodilating Beta Blocker

Refractory HypertensionRefractory Hypertension

• Failure to control BP with 3-4 drugs Failure to control BP with 3-4 drugs including a diuretic. Assess for subtle including a diuretic. Assess for subtle volume overloadvolume overload

• Consider 24 hr Ambulatory BP monitor Consider 24 hr Ambulatory BP monitor

• Consider ReferralConsider Referral

• Consider differential diagnosisConsider differential diagnosis

JNC8 Guidelines for Management of Hypertension

Health & Medicine

Transcript of JNC8 Guidelines for Management of Hypertension