The Jury is Deliberating (JNC 8):Select Cases

Pamela L. Stamm, PharmD, CDE, BCPS

Associate Professor

Auburn University

Harrison School of Pharmacy

December 8, 2011

3

Disclosures

This presenter has nothing to disclose.

Which best describes the frequency in which you select, monitor, or modify therapy in hypertensive

patients?

Daily or most days

A couple of times a week

A couple of times a month

Almost never or never

5

Objectives

Determine when it is appropriate to combine vs. titrate antihypertensive therapy

Recognize select secondary causes of hypertension

Understand the potential role of spironolactone in resistant hypertension

Establish treatment goals in the very elderly

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Marty Graw, 50 yo overweight male, likely hypertensive. C/O fatigue, dry skin, “recent” 10 lb

weight gain, and snoring

Exercise: NA

Diet: Mostly canned

vegetables Lunch meats for

lunch Fresh meats for

supper, occasional “Brat”

Vitals 174/106, 78 bpm, today 168/104, 76 bpm,1 week

ago Pain scale: 2 (1-10)

Current Medications: Simvastatin 20mg QPM Loratidine 10mg daily Multivitamin for men daily

Labs: Chemistry wnl Lipids controlled

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Think – Pair - Share

Take 5 minutes to develop an assessment and plan for this patient

What is your assessment? Stage the HTN Etiology of this patient’s HTN

Plan What lifestyle modifications do you recommend? What labs do you want? What referrals or tests are needed?

Time permitting – share you’re Assessment and Plan with your neighbor

What is his current BP Stage? 174/106 today 168/104 1 week ago

Stage 1

Stage 2

Stage BP ValueNormal <120 / 80Pre-hypertensive 121 –139 / 81 – 89Stage 1 140 – 159 / 90 – 99Stage 2 160 – 179 / 100– 109

Which of the following should be addressed today?

R/O Obstructive Sleep Apnea

R/O Thyroid disease

Diet

Exercise

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Assessment Approach in HTN

Rule out secondary causes OSA Thyroid disease Drug use

Vitals BP, HR, Wt, Pain

Urine protein Chem 7 + eGFR

SCr, BUN, Glucose

Lipid panel 12 lead EKG Possibly TSH

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Treatment Effect of Select Secondary Causesof Hypertension

Secondary causes SBP Change(mmHg)

DBP Change(mmHg)

Obstructive Sleep Apnea 3.4-9.5 3.3-10.5

Hypothyroid 13-37.5 8-21

Hyperthyroid 5

Diet 8-14Physical Inactivity 4-9Weight (-10lb) 5-20

Becker et al. Circulation 2003; 107:68-73. Pepperell et al. The Lancet. 2002;359:204-209. Demellis et al. Am Heart J.

2002; 143:718-24. Iglesias P et al. Clin Endocrinol 2005; 63:66-72. JNC 7. www.nhlbi.nih.gov

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Combining Sodium Reduction and DASH

3.3g 2.5g 1.5g118

120

122

124

126

128

130

132

134

ControlDASH

Sacks F, et al. N Eng J Med 2001; 344: 3-10

Which medication(s) should be started?

Chlorthalidone

Beta blocker

Dihydropyridine CCB + ACEI

HCTZ + ACEI

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Why not maximize a single agent first?

Blood pressure reduction is greater (additive) when drugs are combined compared to titrating the dose Most classes exhibit a poor dose response relationship Gain 1/5 of initial response

Blood pressure goals achieved faster

Lower risk of ADRs compared to dose titration of a single agent

Wald DS, et al. Am J Med. 2009; 122:290-300Law MR, et al. BMJ 2003; 326:1427-34.Gradman AH, et al. JASH 2010; 4:42-50.

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Initial Combinations

Preferred combinations ACE inhibitor / diuretic ▪ ACEI inhibitor / CCB

ARB / diuretic ▪ ARB / CCB

Start with ½ of standard dose Continue home BP monitoring Reassess every 2-4 weeks

Telecare or pt visit

Wald DS, et al. Am J Med. 2009; 122:290-300Law MR, et al. BMJ 2003; 326:1427-34.Gradman AH, et al. JASH 2010; 4:42-50.

Kay Jin, 66 yoa female with HTN, COPD, and OA

Exercise: Walks 35 min. daily

Diet: Low sodium, high in

fruits and vegetables, lean meats

SH: Denies tobacco X 10

yrs 5 oz wine daily

Current Cardiac Medications: Felodipine 10 mg daily Lisinopril 40mg daily HCTZ 25mg daily ASA 81mg daily

Vitals 150/86 today 148/88 last week 142-154/82-88 at home HR 64-72 Wt 140 lbs, BMI 25

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Think – Pair - Share

Take 5 minutes to develop an assessment and plan for this patient

What is your assessment? Stage the HTN

What is your tentative plan? What lifestyle modifications do you recommend? What labs do you want? What referrals or tests are needed? What therapy would you consider?

Time permitting – share you’re Assessment and Plan with your neighbor

Which defines “Resistant HTN”?

Uncontrolled BP despite 2 or more medications

Uncontrolled BP despite 3 or more medications

Controlled BP on > 4 medications

Uncontrolled BP despite 2 or more medications

Uncontrolled BP despite 3 or more medications

Controlled BP on > 4 medications

Calhoun D, et al. Hypertension 2008; 51:1403-1419.

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Causes of Resistant Hypertension

Nonadherence Diet Medications / dietary supplements Obstructive Sleep Apnea Thyroid disease Chronic Kidney Disease (Stage > 4) Primary Aldosteronism Cushings Renal Artery Stenosis Coarctation of the Aorta Pheochromocytoma

How should one manage Resistant HTN?(150/86 today; 148/88 last week; 142-154/82-88 at home)

Send patient for labs, renal US, etc

Switch HCTZ to chlorthalidone

Give trial of spironolactone

Add a 4th antihypertensive of any kind

1

2

2

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HCTZ vs Chlorthalidone

Chlorthalidone 25mg(mmHg)

n=14

HCTZ 50mg(mmHg)

n=16Office readings

Wk 2* -15.7 ± 2.2 -6.1 ± 1.9 -4.5 ± 2.1 -2.9 ± 1.7

Wk 6 -19.6± 3.4 -10.8 ± 3.5

Wk 8 -17.1 ± 3.7 -10.8 ± 3.5

Hypertension 2006; 47: 352-8.

*p<.05

Which of the following statements accurately describe HCTZ?

Majority of BP lowering effect is seen w/ 12.5mg

HCTZ exhibits a flat dose response curve

BP lowering increases significantly up to 50mg

HCTZ may not provide full 24 hour coverage

How should one manage Resistant HTN?(150/86 today; 148/88 last week; 142-154/82-88 at home)

Send patient for labs, renal US, etc

Switch HCTZ to chlorthalidone

Give trial of spironolactone

1

2

2

Adding Spironolactone

Baseline BP

(mmHg)

Median dosemg

(range)

OfficeMean

(95% confidence interval)

24 hrAmbulatory Monitoring

Mean(95% confidence

interval)

De Souza et al 2010

n=175

169 ± 27 50

(25-100)

-14

(9-18)

-7

(4-9)

-16

(13-18)

-9

(4-9)

ASCOT-BPLA

n=1411

156.9/85.3

41 ± 25 -21.9

(20.8-23)

-9.5

(9-10.1)

De Souza F, et al. Hypertension 2010; 55: 147-52.Chapman N, et al. Hypertension 2007; 49: 839-45.

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Summary

Rule out patient factors / common secondary causes

Consider switch to chlorthalidone

Consider trial of spironolactone vs. laboratory testing

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Flor D. Lee, 82 yo female referred to you for HTN management. Started on amlodipine 2.5mg

2 weeks ago.

PMH: HTN, OA

Current medications: ASA 81 mg daily Chlorthalidone 12.5

mg daily Amlodipine 2.5mg

daily Acetaminophen

650mg TID

Diet: 1500 kcal diabetic diet at

local assisted living

Exercise: Chair exercises at local

assisted living

Vitals: 146/78 today 158/84 2 weeks ago 142-150/72-80 home

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Think – Pair - Share

Take 2 minutes to develop an assessment and plan for this patient

What is your assessment? Stage the HTN Define your blood pressure goals

What is your tentative plan? What lifestyle modifications do you recommend? What therapy would you consider?

Time permitting – share you’re Assessment and Plan with your neighbor

Which best describes the BP goal for Flor D. Lee?

<130/80 mmHg

<140/90 mmHg

<150/80 mmHg

<160/90 mmHg

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Trials in the Elderly

Trial Mean Age ISH Mean BPSHEP 72

(60 to > 80)Y 144/68

Sys-Eur 70 (> 60)

Y 151/79

VALISH 76(70-84)

Y 137/75

STOP 76 (70-84)

N 157/87

MRCOA 70 (65-74)

N 152/77

JAMA 1991;265:3255–64. Lancet 1997; 350(9080):757-64. Hypertension. 2010; 56: 196-202. Blood Press. 2004;13(3):137-41. BMJ. 1992 Feb 15;304(6824):405-12.

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Hypertension in the Very Elderly (HYVET; n=3845)

Rate per 1000 patient-years

Treatment Placebo HR (95% CI)

Stroke 12.4 17.7 .7 (.49-1.01)

Stroke mortality 6.5 10.7 .61 (.38-.99)

Any cardiovascular event

33.7 50.6 .66(.53-.82)

Total mortality 47.2 59.6 .79 (.65-.95)

Beckett NS, et al. NEJM 2008; 358:1887-98.

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Hypertension in the Very Elderly (HYVET; 3845)

Sitting Blood Pressure

Treatment Placebo

Baseline 173 ± 8.4 173 ± 8.6

At 2 years 143.5 ± 15.4 158.5 ± 13.5

Baseline 90.8 ± 8.4 90.8 ± 8.5

At 2 years 77.9 ± 9.5 84 ± 10.5

Beckett NS, et al. NEJM 2008; 358:1887-98.

Which best describes the BP goal for Flor D. Lee?

<140/90 mmHg

<150/80 mmHg

<160/90 mmHg

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Which best describes the BP goal for Flor D. Lee?

American Heart Association:

Target SBP < 140-145 and > 130 mmHg

American Heart Association:

Target SBP < 140-145 and > 130Aronow WS, et al. J Am Coll Cardiol, 2011; 57:2037-2114.

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J-Curve for Diastolic Blood Pressure

Risk increases with DBP < 60-65-70 mmHg

American Heart Association Keep DBP > 65mmHg

Safar H, et al. HTN 2007; 50: 172-180. Fagard RH, et al. Arch Intern Med. 2007;167(17):1884-1891.

Aronow WS, et al. J Am Coll Cardiol, 2011; 57:2037-2114.

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Summary

In Stage 2 or higher, consider combination therapy using low doses

When titrating, consider combining therapies prior to maximizing dose

Rule out common secondary causes prior to treating hypertension

Consider spironolactone for resistant hypertension Consider the evidence when establishing the BP

target for the very elderly

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JNC 8 update from AHA

1. Does initiating antihypertensive pharmacological therapy at specific BP thresholds improve health outcomes? When should you initiate treatment?

2. Does treatment with an antihypertensive pharmacological therapy to a specified BP goal lead to improvements in health outcomes? How low should you go?

3. Do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes? How do you get there?

Only using RCT evidence…….

http://www.theheart.org/article/1310865.do