Refractory Hypertension 020310a

7/29/2019 Refractory Hypertension 020310a

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Refractory Hypertension:Four Cases

Paul R. Chelminski, MD, MPH, FACP

Associate Professor of Medicine

Associate Residency Program Director


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Objectives

1.Review JNC-7 Guidelines

2.Understand common barriers to achieving

blood pressure control3.Review some causes of secondary

hypertension.

4.Review recent advances in ourunderstanding of the HTN management


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JNC-7* Highlights

CVD risk doubles with each 20/10mmHgincrement over 115/75

SBP more important CV risk factor

Two or more agents usually required

Thiazides are first choice and first line

Consider 2 agents if BP >20/10 above goal

Targets 140/90

130/80 if diabetic or CKD

*Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High

Blood Pressure, 7th Report http://www.nhlbi.nih.gov/guidelines/hypertension/express.pdf.
http://www.nhlbi.nih.gov/guidelines/hypertension/express.pdfhttp://www.nhlbi.nih.gov/guidelines/hypertension/express.pdf


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HTN Classification


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Meds: Compelling Indications


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HTN Control: Clinical Impact

Decreased CVD Incidence

Stroke:35-40%

MI: 20-25% CHF: >50%

12mmHg BP reduction over 10 yrs willprevent one death in every 11 patients

NNT is 9 patients with underlying CVD ortarget organ damage


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BP Control in Clinical Settings

>70% non-diabetic & diabetic patients withsub-optimal control

91% adherent to regimens 70% taking fewer than 3 antihypertensives

Therapeutic Inertia:

45% did not have therapy intensified at first f/uvisit

36% had no change at 2nd f/u visit


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Challenges to ImprovingBlood Pressure Control

Four Cases of Refractory

Hypertension


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Barriers to HTN control

Cost

Medication side effects

Lack of gratifying response to therapy(patient does not feel better)

Need for lifestyle changes

Tedium: titration- requiring multiple visits &close monitoring by MD & patient


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Case 1

Visit 1 61 yo female with HTN, hyperparathyroidism,

h/o DVT Presents with pins & needles in LEs Meds

coumadin, Sensipar amlodipine, lisinopril, furosemide, HCTZ, metoprolol

Social Hx: non-smoker,uninsured BP 194/129 (re-check, 172/111); ?non-

adherence to one medication; recent SBPs~140

Labs: Na 145, K 3.7, Cr 0.8, Ca 11.7, B12 465

Dispo: Restart meds & f/u 4 days


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Case 1

Visit 2

c/o Fatigue

Patient confirms medications

BP 204/132 (re-check, 210/135)

Receives clonidine in clinic & admitted for

hypertensive urgency & management ofhypercalcemia


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Case 1

Hospitalization & Visit 3

Hydrated with decrease in Ca++

Source of HTN identified: non-adherence d/tinability to afford meds

D/C Meds: lisinopril, metoprolol, furosemide

(Walmart $4drugs to rescue) BP at f/u 147/101

Amlodipine added


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Obstacles to Optimizing HTNManagement

Adherence Cost Literacy!

Clinical Uncertainty 50% doctors dont intervene due to uncertainty about

accuracy of triage BP (home blood pressures lower)

Competing Medical Demands Trial evidence conflicting about influence of multiple

comorbididities Time constraints

Largely unstudied


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Case 2

54 yo female with HTN, diabetes,hypercholesterolemia

BP Meds: amlodipine, lisinopril, HCTZspironolactone

BP 7/09: 166/83; A1c 9.0%: Substitutechlorthalidone for HCTZ

BP 1/09: 164/68; A1c: 7.3%: ?Non-adherence to one med


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Case 2

Social Hx: No tobacco; no ETOH; h/ococaine use but denies current.


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Drugs That Cause HTN

Drugs of abuse Cocaine, methamphetamine Alcohol

OTC decongestants Prescription

Venlafaxine/SNRIs Estrogens/OCPs Corticosteroids

Namenda Erythropoietin Tacrolimus/Cyclosporin


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Case 3

62 yo male with HTN, palpitations, myalgias

Meds: felodipine (5mg), atenolol (100mg),benazepril (20mg), minoxidil (10mg prn elevated

BP), KCL 80mEq/d Social: no tobacco; retired farmer

ROS: no CP, no SOB/DOE, no syncope

BP 182/99, P 64. +S4 gallop Labs: K+ 2.8; aldo 90, renin


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Case 3

Dx: Hyperaldosteronism

Etiology: Adrenal adenoma (rare malignancy),adrenal hyperplasia

W/U: Aldo/Renin: Ratio >30 suggests primary

hyperaldosteronism

MRI of abdomen

Rx Medical: spironolactone

?Surgery


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Case 3: Denouement

Spironolactone, 100mg bid started

Orthostasis at home with SBPs in 70s

Decreased minoxidil to 5mg/d and atenololto 50mg/d

BP 139/90

K+ (4.7)-palpitations, myalgias resolved.


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Case 4 77yo female with refractory HTN, diet

controlled DM, obesity, OA


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Case 4

BP 159/79 (Re-check, 160/79)

ROS: Daytime sleepiness, snoring, night-

time arousals K+ 4.1, Cr 0.87

Sleep study: OSA

Denouement: Awaiting outcome of CPAPtrial


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The ACCOMPLISH Trial


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Study objective

Comparison of cardiovascular events betweengroup treated with combination benazepril-HCTZversus combination benazepril-amlodipine, withhypothesis that benazepril-amlodipine would besuperior in reducing cardiovascular events.

HCTZ


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Study design

Total 11,506 patients recruited for study

Multi-center

Randomized, double-blind trial Similar patient demographic and co-

morbidities in each group

Intention to treat model


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Who are the patients?

This study has a highpredominance of patientswho are elderly, obese,Caucasian, have multipleco-morbidities (includingdiabetes, dyslipidemia,and CAD), and difficult tocontrol HTN, requiring

multiple agents.

at high risk for cardiac events


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Who are the patients?

38% Receiving 3 or more drugs atenrolment

Only 37% had BP


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Study procedures(contd)

Algorithm outlined by study foroptimization of blood pressurecontrol

Patient randomized

20 mg benazepril

5 mg amlodipine20 mg benazepril

12.5 mg HCTZ

One month

BP > 140/90 without diabetes

OR

BP > 130/80 with diabetes

40 mg benazepril

5 mg amlodipine

40 mg benazepril

12.5 mg HCTZ


OR


Yes YesNo No

Continue current

regimen

Continue current

regimen

40 mg benazepril

10 mg amlodipine

40 mg benazepril

25 mg HCTZ

Three months


OR



OR


Six

months

Add other agents

Eg beta blocker, alpha blocker,

clonidine, spironolactone


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Study Endpoints

Primary endpoint

Time to first event

One event per patient

Composite of acardiovascular eventand death from

cardiovascular causes

Secondary endpoints

Multiple eventscounted for a patient

Including composite ofcardiovascular events,hospitalization from

heart failure, deathfrom any cause


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Results: Improved BP Control

Both benazepril/ amlodipine and benazepril/HCTZ combination therapy improved bloodpressure control

Amlodipine HCTZ

Mean SBP 131.6 132.5

Mean DBP 73.3 74.4

% BP


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Results: CV Mortality and Events

Benazepril/amlodipine group saw:

Decreased primary endpoints at 30 mos.

Decrease secondary endpoints: death fromCV causes, non-fatal MI< stroke

Early cessation of study by safety &

monitoring committee when pre-specifiedthresholds for termination seen in Ace/CCBarm d/t efficacy


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Kaplan-Meier Curve:Time to First Primary Composite Endpoint


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Results: Primary Endpoints

Primaryendpoint at30 months

Benazepril/Amlodipine(%)

Benazepril/HCTZ(%)

ARR(EER-CER)(%)

RRR(ARR/CER)(%)

All 9.6 11.8 2.2 19.6

Male 10.6 13.1 2.5 19Female 8.1 9.7 1.6 16.4

Age >65 10.1 12.4 2.3 18.5

Age >70 11 13.8 2.8 20.2

+DM 8.8 11 2.2 20

- DM 10.8 12.9 2.1 16.2


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Drug Costs

Drug name Cost for 30 day supply

Enalapril 5 mg -20 mg $4

HCTZ 12.5-25 mg $4

Atenolol 25 mg- 100 mg $4

Amlodipine (Norvasc) 5 mg $75

Amlodipine (generic) 5 mg $21

Adapted from Blue Cross Blue Shield of North Carolina and WalMart$4 pharmacy list

90 supply available from Drugstore.com for $18

Refractory Hypertension 020310a

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