Download Hypertension Lecture

Daily Dilemmas in
Hypertension Management
Objectives
Review the impact of hypertension on
society
 Review several current questions in
hypertension management

Joint National Committee (JNC7)
BP Classification
SBP
DBP
Normal
<120
Pre Hypertension
120-139
or
80-89
Stage I Hypertension
140 – 159
or
90 - 99
Stage II Hypertension
> 160
or
> 100
and
<80
Prevalence (%)
Prevalence of Hypertension in the US
1999-2004
100
80
60
40
20
0
66.3
32.6
7.3
18 - 39
40 - 59
> 59
Age
Ong, et al. Hypertension, 2007
Healthy People 2010
Reduce prevalence of HTN to 16% (at
28% in 2000)
 Target 50% overall hypertension control
rate
 Target 95% intervention rate (including life
style modification)

Trends in Hypertension Awareness
and Treatment
Percent (%)
100
80
68 71
76
60
58 60
65
40
2000
2002
2004
20
0
Awareness
Treatment
Ong, et al. Hypertension, 2007
Overall Hypertension Control
Percent at Goal (%)
100
80
60
50
40
29
33
54
57
36 38
37
24
2000
2002
2004
20
0
Hypertension
On Treament
Diabetics
Treatment Group
Ong, et al. Hypertension, 2007
Treatment of Hypertension
Lifestyle Modifications
Not at Goal Blood Pressure
Initial Drug Choices
Without Compelling
Indications
With Compelling
Indications
Stage 1 Hypertension
Stage 2 Hypertension
Thiazide-type diuretics for most.
May consider ACEI, ARB, BB, CCB,
or combination.
2-drug combination for most (usually
thiazide-type diuretic and
ACEI, or ARB, or BB, or CCB)
Drug(s) for the compelling
indications
Other antihypertensive drugs
(diuretics, ACEI, ARB, BB, CCB)
as needed.
Not at Goal
Optimize dosages or add additional drugs
until goal blood pressure is achieved.
Adapted from JNC7
Treatment Options
Diuretics
Thiazides
Chlorthalidone
Indapamide
Metolazone
Thiazides
Loops
Bumetanide
Furosimide
Toremide
Aldosterone
blockers
Spironaldactone
Eplerenone
Potassium
sparers
Amiloride
Triamterene
Adrenergic
Blockers
Peripheral
Inhibitors
Guanadrel
Guanethidine
Reserpine
Central alphaagonists
Clonidine
Guanzbenz
Guanfacine
Methyldopa
Alpha-blockers
Dozazosin
Prazosin
Terazosin
Vasodilators
Beta-blockers
Direct
ACE-I
Acebutol
Atenolol
Betaxolol
Bisoprolol
Carteolol
Metoprolol
Nadolol
Penutolol
Pindolol
Propranolol
Timolol
Hydralazine
Minoxidil
Benazepril
Captopril
Enalapril
Fosinopril
Lisinopril
Moexipril
Quinapril
Perindopril
Ramipril
Trandolapril
Combined
Carvediol
Labetolol
Calcium channel
blocker
Dihydropyridines
Amlodipine
Felodipine
Isradipine
Nicardipine
Nifedipine
Nisoldipine
Diltiazem
Verapamil
Direct renin
antagonist
Aliskiren
ARB
Candesartan
Eprosartan
Irbesartan
Losartan
Telmisartan
Valsartan
Comparisons of Therapy
The Lancet, Volume 362, Issue 9395, 2003
Benefits of Lowering Blood
Pressure
Average Percent Reduction
Stroke incidence
35–40%
Myocardial infarction
20-25%
Heart failure
50%
Question #1

I have a 86 year-old Caucasian female
patient with osteoporosis and a history of
breast cancer. Here clinic blood pressure
is always 190/80.

What should be her target systolic blood
pressure?
Scope of the Problem
Mean Systolic and Diastolic BP by Age and Race/Ethnicity for Men and
Women (US Population ³Age 18 Years, NHANES III)
150
130
110
Non-Hispanic Black
Non-Hispanic White
Mexican American
SBP
(mm Hg)
SBP
(mm Hg)
150
110
DBP
(mm Hg)
80
70
70
0
150
150
SBP
(mm Hg)
0
130
110
130
110
Pulse pressure
80
Pulse pressure
80
DBP
(mm Hg)
SBP
(mm Hg)
DBP
(mm Hg)
80
DBP
(mm Hg)
130
70
0
18-29 30-39 40-49 50-59 60-69 70-79
Men, Age (y)
80+
70
0
18-29 30-39 40-49 50-59 60-69 70-79
80+
Women, Age (y)
Burt VI, et al. Hypertension. 1995;25:305-313.
Benefits of Lowering Blood
Pressure
Average Percent Reduction
Stroke incidence
35–40%
Myocardial infarction
20-25%
Heart failure
50%
Cumulative stroke rate
per 100 persons
SHEP Cumulative Stroke Rate
10
9
8
7
6
5
4
3
2
1
0
P=0.0003
36% reduction in stroke rate
Placebo
(n=2,371)
Active Rx
(n=2,365)
0
12
24
36
48
60
72
Months of follow-up
SHEP=Systolic Hypertension in the Elderly Program
SHEP Research Group. JAMA. 1991;265:3255-3264.
Copyright ©1991, American Medical Association.
Hypertensiononline.org
Relative risk (95% CI)
SHEP Cardiovascular Disease Endpoints
1.60
Active Therapy vs. Placebo
1.40
1.20
1.00
0.80
0.60
0.87
0.63
0.46
0.40
0.20
0.68
0.75
Stroke
CHD
CHF
CVD
Death
CHD=coronary heart disease; CHF=congestive heart failure; CVD=cardiovascular disease
SHEP=Systolic Hypertension in the Elderly Program
SHEP Research Group. JAMA. 1991;265:3255-3264.
Hypertensiononline.org
Survival free of event (%)
EWPHE Cardiovascular Mortality
On-Treatment Analysis
P=0.023
100
Active (n=416)
90
Placebo
(n=424)
80
70
0
1
2
3
4
Year of follow-up
5
6
7
EWPHE=European Working Party on High Blood Pressure in the Elderly
Amery A, et al. Lancet. 1985;1:1349-1354.
Reprinted with permission from Elsevier Science.
Hypertensiononline.org
Blood Pressure & The Very Elderly

Epidemiologic population studies suggest
better survival with higher levels of blood
pressure

Worse survival reported in hypertensives
with SBP levels below 140 mmHg (Oates et al.
2007)

Meta-analysis (n=1670)


(Gueyffier et al. 1997)
36% reduction in the risk of stroke (BENEFIT)
14% (p=0.05) increase in total mortality (RISK)
The Trial:
International, multi-centre, randomised double-blind placebo controlled
Inclusion Criteria:
Aged 80 or more,
Systolic BP; 160 -199mmHg
+ diastolic BP; <110 mmHg,
Informed consent
Exclusion Criteria:
Standing SBP < 140mmHg
Stroke in last 6 months
Dementia
Need daily nursing care
CHF or Cr more than 1.7
Primary Endpoint:
All strokes (fatal and non-fatal)
+ Perindopril 4 mg
+ Perindopril 2 mg
Indapamide SR 1.5 mg
Target blood pressure
Placebo
150/80 mmHg
Placebo
+ Placebo
+ Placebo
M-2
M-1
M0
M3
M6
M9
M12
M18
M24
M60
All stroke
(30% reduction)
Placebo
IndapamideSR ±perindopril
Heart Failure
(64% reduction)
Total Mortality
(21% reduction)
Conclusions

Antihypertensive treatment based on indapamide ±
perindopril reduced stroke mortality and total
mortality in a very elderly cohort.

NNT (2 years) = 94 for stroke and 40 for mortality

Large and significant benefit in reduction of heart
failure events and for combined endpoint of
cardiovascular events

Goal blood pressure was 150/80
INVEST Trial Secondary analysis

The risk for the
primary endpoint
(death, myocardial
infarction, or stroke)
progressively
increased with low
diastolic blood
pressure.
AIM 144:884 (2006)
Conclusions

Evidence supports moderate blood
pressure reduction in the very elderly to
goal of 150/80

Excessive reduction of diastolic pressure
may have adverse consequences
My Patient

Target blood pressure of 150/80

Achieve goal with low dose thiazide diurectic

Consider ACE-I or CCB for combination
therapy

Monitor home blood pressures
 Consider
titrating to standing blood pressure
Question #2

Is combination therapy with an
angiotensin-converting enzyme inhibitor
(ACE) and an angiotensin receptor blocker
(ARB) appropriate for my patient with
essential hypertension requiring an
additional agent to reach goal?
Renin-Angiotensin Pathway
www.kidney.org
Practice Trends

Since 2000, several trials compared dual
ACE-ARB therapy in nephropathy and
coronary disease


COOPERATE, CHARM, VALLIANT,
ONTAGERT
General thought: More blockade must be
better
COOPERATE

Evaluated combination of losartan and
trandolapril in non-diabetic proteinuric
renal disease

Significant benefit from combination
therapy in slowing progression of disease

Publication retracted by the Lancet in
October 2009
Lancet 2009 Oct 9;374(9697):1226
Lancet 2003 Jan 11;361(9352):117-24

ACE and ARB medications equally reduce
proteinuria

Combination therapy has greater effect

Unable to assess outcomes
Ann Intern Med. 2008 Jan 1;148(1):30-48
ONTARGET

Effects of telmisartan, ramipril, or both on
death from cardiovascular causes, MI,
stroke, or hospitalization for heart failure

No significant difference in primary
outcomes between any arms
NEJM 2008; 358:1547-1559
ONTARGET Dual Therapy

Average BP reduction of 2-3 mmHg in
combination arm
Expected 4-5% reduction in primary outcome
not found
 Significant increases in:

 Hypotension
 Hyperkalemia
 Renal
dysfunction
 Syncope
NEJM 2008; 358: 1547-1559
ONTARGET Conclusions
Patients who have vascular disease or
high risk diabetes, telmisartan is not
inferior to ramipril
 No additional benefit from combination
therapy

Significantly more risk
 BP reduction not beneficial

NEJM 2008; 358: 1547-1559
My Patient

ACE or ARB is appropriate

Combination therapy not routinely
indicated for blood pressure reduction
Specific populations may have benefit from
combination therapy
 Consider other options for proteinuria
reduction if indicated

Question #3

I have a 50 year-old male patient with
elevated systolic blood pressures over 160
mmHg at every clinic visit. His home
blood pressure is always less than 130
mmHg.

What is his cardiovascular risk from his
elevated clinic readings?
Systolic Change from Baseline
(mmHg)
Blood Pressure Response to
Physician or Nurse
25
20
Physician
15
Nurse
10
5
0
Peak
5 Minutes
10 Minutes
Time
Hypertension 1987;9:209
White Coat Hypertension

Definition:
Daytime blood pressure average less than
130/80 mmHg
 Clinic readings greater than 140/90 mmHg


White Coat Effect

Elevated pressure in the clinic superimposed
on essential hypertension
Scope of the Problem

Prevalence range 10 – 30% of patients
with clinical hypertension
Diagnosis of hypertension usually made on
clinic blood pressure recordings
 10% - 74% will progress to hypertension over
5 years


Historically considered a benign condition
% of Patients
Outcomes in White Coat
Hypertension (WCH)
20
18
16
14
12
10
8
6
4
2
0
P<0.001
15.3
WCH
7.9
NS
3.2
Sustained
HTN
P<0.001
3.7
3.7
0.8
Non Cardiac
Death
CVA
Coronary
Event
Khatter et al, Circulation. 1998;98:1892
Analysis of data from 4 cohort studies in 3
countries
 Followed for a median 5.3 years


Evaluated incidence of stroke
Hypertension. 2005;45:203-208
Results

Significant increased risk of stroke from:
Elevated office and sleep systolic pressure
 Tobacco use
 Older age
 Diabetes


No clear significant increased risk from
white coat hypertension
Six-Year Risk-Factor Adjusted
Probability of Stroke
Non-Smokers
Smokers
Probability
8
6
Normotensive
WCH
HTN
4
2
0
Women
Men
Women
Men
Hypertension. 2005;45:203-208
Cumulative Hazard for Stroke
Hypertension. 2005;45:203-208
Conclusions

Patients with white coat hypertension are
at risk for progression to hypertension,
likely greater than a normotensive cohort

While the cardiovascular risk from WCH is
less than with hypertension, it may still
carry some risk
My Patient

Cardiac risk stratification from other risk
factors

Lifestyle modification
 Low
sodium diet
 Regular exercise
Occasional home blood pressure monitoring
 Consider 24 hour ambulatory blood pressure
monitor

Conclusions

To meet blood pressure goals we must:
Make the diagnosis more frequently
 Educate our patients
 Treat more aggressively, with simple
medication regimens
 Reassess to reach goals

Thank you
Resources
Amery A, et al. Lancet. 1985;1:1349-1354.
Ann Med 2006; 144:884
Burt VI, et al. Hypertension. 1995;25:305-313.
Hypertension. 1987;9:209
Hypertension. 2005;45:203-208
Khatter et al; Circulation. 1998;98:1892
Lancet 2003;361(9352):117-24
Lancet 2003; 362 (9395):
Ong, et al. Hypertension. 2007
SHEP Research Group. JAMA. 1991;265:3255-3264.