Transcript Refractory Hypertension: Three Cases

Refractory Hypertension:
Four Cases
Paul R. Chelminski, MD, MPH, FACP
Associate Professor of Medicine
Associate Residency Program Director
Objectives
1.Review JNC-7 Guidelines
2.Understand common barriers to achieving
blood pressure control
3.Review some causes of secondary
hypertension.
4.Review recent advances in our
understanding of the HTN management
JNC-7* Highlights
 CVD risk doubles with each 20/10mmHg
increment 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.
HTN Classification
Meds: Compelling Indications
HTN Control: Clinical Impact
 Decreased CVD Incidence
– Stroke:35-40%
– MI: 20-25%
– CHF: >50%
 12mmHg BP reduction over 10 yrs will
prevent one death in every 11 patients
 NNT is 9 patients with underlying CVD or
target organ damage
BP Control in Clinical Settings
 >70% non-diabetic & diabetic patients with
sub-optimal control
 91% adherent to regimens
 70% taking fewer than 3 antihypertensives
 “Therapeutic Inertia”:
– 45% did not have therapy intensified at first f/u
visit
– 36% had no change at 2nd f/u visit
Challenges to Improving
Blood Pressure Control
Four Cases of Refractory
Hypertension
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
Case 1
Visit 1
 61 yo female with HTN, hyperparathyroidism,
h/o DVT
 Presents with “pins & needles” in LE’s
 Meds
– coumadin, Sensipar
– amlodipine, lisinopril, furosemide, HCTZ, metoprolol
 Social Hx: non-smoker,uninsured
 BP 194/129 (re-check, 172/111); ?nonadherence to one medication; recent SBP’s
~140
 Labs: Na 145, K 3.7, Cr 0.8, Ca 11.7, B12 465
 Dispo: Restart meds & f/u 4 days
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 of
hypercalcemia
Case 1
Hospitalization & Visit 3
 Hydrated with decrease in Ca++
 Source of HTN identified: non-adherence d/t
inability to afford meds
 D/C Meds: lisinopril, metoprolol, furosemide
(Walmart $4drugs to rescue)
 BP at f/u 147/101
 Amlodipine added
Obstacles to Optimizing HTN
Management
 Adherence
– Cost
– Literacy!
 Clinical Uncertainty
– 50% doctors don’t 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
Case 2
 54 yo female with HTN, diabetes,
hypercholesterolemia
 BP Meds: amlodipine, lisinopril, HCTZ
spironolactone
 BP 7/09: 166/83; A1c 9.0%: Substitute
chlorthalidone for HCTZ
 BP 1/09: 164/68; A1c: 7.3%: ?Nonadherence to one med
Case 2
 Social Hx: No tobacco; no ETOH; h/o
cocaine use but denies current.
Drugs That Cause HTN
 Drugs of abuse
– Cocaine, methamphetamine
– Alcohol
 OTC decongestants
 Prescription
–
–
–
–
–
–
Venlafaxine/SNRIs
Estrogens/OCP’s
Corticosteroids
Namenda
Erythropoietin
Tacrolimus/Cyclosporin
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 <0.2 (ratio=450)
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
Case 3: Denouement
 Spironolactone, 100mg bid started
 Orthostasis at home with SBP’s in 70’s
 Decreased minoxidil to 5mg/d and atenolol
to 50mg/d
 BP 139/90
 K+ (4.7)-palpitations, myalgias resolved.
Case
4
 77yo female with refractory HTN, diet
controlled DM, obesity, OA
Case 4
 BP 159/79 (Re-check, 160/79)
 ROS: Daytime sleepiness, snoring, nighttime arousals
 K+ 4.1, Cr 0.87
 Sleep study: OSA
 Denouement: Awaiting outcome of CPAP
trial
The ACCOMPLISH Trial
Study objective
Comparison of cardiovascular events between
group treated with combination benazepril-HCTZ
versus combination benazepril-amlodipine, with
hypothesis that benazepril-amlodipine would be
superior in reducing cardiovascular events.
HCTZ
Study design




Total 11,506 patients recruited for study
Multi-center
Randomized, double-blind trial
Similar patient demographic and comorbidities in each group
 Intention to treat model
Who are the patients?
This study has a high
predominance of patients
who are elderly, obese,
Caucasian, have multiple
co-morbidities (including
diabetes, dyslipidemia,
and CAD), and difficult to
control HTN, requiring
multiple agents.
“at high risk for cardiac events”
Who are the patients?
 38% Receiving 3 or more drugs at
enrolment
 Only 37% had BP <140/70
 60% had diabetes
 Average age 68yrs (fairly geriatric)
Patient randomized
Study procedures
(cont’d)
20 mg benazepril
5 mg amlodipine
20 mg benazepril
12.5 mg HCTZ
Algorithm outlined by study for
optimization of blood pressure
control
One month
40 mg benazepril
5 mg amlodipine
40 mg benazepril
12.5 mg HCTZ
Three months
BP > 140/90 without diabetes
OR
BP > 130/80 with diabetes
No
Yes
Continue current
regimen
BP > 140/90 without diabetes
OR
BP > 130/80 with diabetes
Yes
40 mg benazepril
10 mg amlodipine
BP > 140/90 without diabetes
OR
BP > 130/80 with diabetes
40 mg benazepril
25 mg HCTZ
Six
months
BP > 140/90 without diabetes
OR
BP > 130/80 with diabetes
Add other agents
Eg beta blocker, alpha blocker,
clonidine, spironolactone
No
Continue current
regimen
Study Endpoints
Primary endpoint
 Time to first event
 One event per patient
 Composite of a
cardiovascular event
and death from
cardiovascular causes
Secondary endpoints
 Multiple events
counted for a patient
 Including composite of
cardiovascular events,
hospitalization from
heart failure, death
from any cause
Results: Improved BP Control
 Both benazepril/ amlodipine and benazepril/
HCTZ combination therapy improved blood
pressure control
Amlodipine
HCTZ
Mean SBP
131.6
132.5
Mean DBP
73.3
74.4
% BP <140/90
75.4
72.4
Results: CV Mortality and Events
Benazepril/amlodipine group saw:
 Decreased primary endpoints at 30 mos.
 Decrease secondary endpoints: death from
CV causes, non-fatal MI< stroke
 Early cessation of study by safety &
monitoring committee when pre-specified
thresholds for termination seen in Ace/CCB
arm d/t efficacy
Kaplan-Meier Curve:
Time to First Primary Composite Endpoint
Results: Primary Endpoints
Primary
endpoint at
30 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
19
Female
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
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