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
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
6
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
7
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
10
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
11
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
12
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
14
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.
15
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
17
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.
19
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
21
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.
25
Summary
Rule out patient factors / common secondary causes
Consider switch to chlorthalidone
Consider trial of spironolactone vs. laboratory testing
26
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
27
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
29
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.
30
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.
31
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.
33
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.
34
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.
35
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
36
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
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