daily dilemmas in hypertension management. objectives review the impact of hypertension on society...
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Daily Dilemmas in Daily Dilemmas in Hypertension ManagementHypertension Management
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ObjectivesObjectives
Review the impact of hypertension on Review the impact of hypertension on societysociety
Review several current questions in Review several current questions in hypertension managementhypertension management
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Joint National Committee (JNC7)Joint National Committee (JNC7)
BP Classification SBP DBPBP Classification SBP DBP
Normal <120 and <80Normal <120 and <80
Pre Hypertension 120-139 or 80-89Pre Hypertension 120-139 or 80-89
Stage I Hypertension 140 – 159 or 90 - 99Stage I Hypertension 140 – 159 or 90 - 99
Stage II Hypertension > 160 or > 100Stage II Hypertension > 160 or > 100
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7.3
32.6
66.3
0
20
40
60
80
100
Pre
vale
nce
(%
)
18 - 39 40 - 59 > 59
Age
Prevalence of Hypertension in the US 1999-2004
Ong, et al. Hypertension, 2007
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Healthy People 2010Healthy People 2010
Reduce prevalence of HTN to 16% (at Reduce prevalence of HTN to 16% (at 28% in 2000)28% in 2000)
Target 50% overall hypertension control Target 50% overall hypertension control raterate
Target 95% intervention rate (including life Target 95% intervention rate (including life style modification)style modification)
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68 71 76
58 60 65
0
20
40
60
80
100
Per
cen
t (%
)
Awareness Treatment
Trends in Hypertension Awareness and Treatment
200020022004
Ong, et al. Hypertension, 2007
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2933
37
5054
57
24
36 38
0
20
40
60
80
100
Pe
rce
nt
at
Go
al
(%)
Hypertension On Treament Diabetics
Treatment Group
Overall Hypertension Control
200020022004
Ong, et al. Hypertension, 2007
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Treatment of HypertensionTreatment of Hypertension
Not at Goal Blood Pressure
Initial Drug Choices
Drug(s) for the compelling indications
Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB)
as needed.
With Compelling Indications
Lifestyle Modifications
Stage 2 Hypertension 2-drug combination for most
(usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB)
Stage 1 Hypertension Thiazide-type diuretics for most.
May consider ACEI, ARB, BB, CCB,
or combination.
Without Compelling Indications
Not at Goal
Optimize dosages or add additional drugs until goal blood pressure is achieved.
Adapted from JNC7
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Treatment OptionsTreatment OptionsDiureticsDiuretics Adrenergic Adrenergic
BlockersBlockersVasodilatorsVasodilators
ThiazidesThiazidesChlorthalidoneChlorthalidone
IndapamideIndapamide
MetolazoneMetolazone
ThiazidesThiazides
LoopsLoopsBumetanideBumetanide
FurosimideFurosimide
ToremideToremide
Aldosterone Aldosterone blockersblockersSpironaldactoneSpironaldactone
EplerenoneEplerenone
Potassium Potassium sparerssparersAmilorideAmiloride
TriamtereneTriamterene
Peripheral Peripheral InhibitorsInhibitorsGuanadrelGuanadrel
GuanethidineGuanethidine
ReserpineReserpine
Central alpha-Central alpha-agonists agonists ClonidineClonidine
GuanzbenzGuanzbenz
GuanfacineGuanfacine
MethyldopaMethyldopa
Alpha-blockersAlpha-blockersDozazosinDozazosin
PrazosinPrazosin
TerazosinTerazosin
Beta-blockersBeta-blockersAcebutolAcebutol
AtenololAtenolol
BetaxololBetaxolol
BisoprololBisoprolol
CarteololCarteolol
MetoprololMetoprolol
NadololNadolol
PenutololPenutolol
PindololPindolol
PropranololPropranolol
TimololTimolol
CombinedCombinedCarvediolCarvediol
LabetololLabetolol
DirectDirectHydralazineHydralazine
MinoxidilMinoxidil
Calcium channel Calcium channel blockerblockerDihydropyridinesDihydropyridines
AmlodipineAmlodipine
FelodipineFelodipine
IsradipineIsradipine
NicardipineNicardipine
NifedipineNifedipine
NisoldipineNisoldipine
DiltiazemDiltiazem
VerapamilVerapamil
Direct renin Direct renin antagonistantagonistAliskirenAliskiren
ACE-IACE-IBenazeprilBenazepril
CaptoprilCaptopril
EnalaprilEnalapril
FosinoprilFosinopril
LisinoprilLisinopril
MoexiprilMoexipril
QuinaprilQuinapril
PerindoprilPerindopril
RamiprilRamipril
TrandolaprilTrandolapril
ARBARBCandesartanCandesartan
EprosartanEprosartan
IrbesartanIrbesartan
LosartanLosartan
TelmisartanTelmisartan
ValsartanValsartan
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The Lancet, Volume 362, Issue 9395, 2003
Comparisons of TherapyComparisons of Therapy
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Benefits of Lowering Blood Benefits of Lowering Blood PressurePressure
Average Percent Average Percent
ReductionReduction
Stroke incidence Stroke incidence 35–40%35–40%
Myocardial infarctionMyocardial infarction 20-25%20-25%
Heart failureHeart failure 50% 50%
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Question #1Question #1
I have a 86 year-old Caucasian female I have a 86 year-old Caucasian female patient with osteoporosis and a history of patient with osteoporosis and a history of breast cancer. Here clinic blood pressure breast cancer. Here clinic blood pressure is always 190/80.is always 190/80.
What should be her target systolic blood What should be her target systolic blood pressure?pressure?
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Scope of the ProblemScope of the Problem
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18-29 30-39 40-49 50-59 60-69 70-79 80+0
70
80
110
130
150
18-29 30-39 40-49 50-59 60-69 70-79 80+0
70
80
110
130
150
0
70
80
110
130
150
0
70
80
110
130
150D
BP
(mm
Hg
)S
BP
(mm
Hg
)D
BP
(mm
Hg
)S
BP
(mm
Hg
)
DB
P(m
m H
g)
SB
P(m
m H
g)
DB
P(m
m H
g)
SB
P(m
m H
g)
Men, Age (y) Women, Age (y)
Non-Hispanic BlackNon-Hispanic WhiteMexican American
Pulse pressure Pulse pressure
Mean Systolic and Diastolic BP by Age and Race/Ethnicity for Men and Women (US Population ³Age 18 Years, NHANES III)
Burt VI, et al. Burt VI, et al. HypertensionHypertension. 1995;25:305-313. 1995;25:305-313..
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Benefits of Lowering Blood Benefits of Lowering Blood PressurePressure
Average Percent Average Percent
ReductionReduction
Stroke incidence Stroke incidence 35–40%35–40%
Myocardial infarctionMyocardial infarction 20-25%20-25%
Heart failureHeart failure 50% 50%
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0123456789
10
Cu
mu
lati
ve s
troke r
ate
p
er
10
0 p
ers
on
s
0 12 36 60Months of follow-up
SHEP Cumulative Stroke RateSHEP Cumulative Stroke Rate
24 48 72
P=0.0003
Placebo(n=2,371)
Active Rx (n=2,365)
SHEP=Systolic Hypertension in the Elderly Program
SHEP Research Group. JAMA. 1991;265:3255-3264.Copyright ©1991, American Medical Association. Hypertensiononline.org
36% reduction in stroke rate
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0.20
0.40
0.60
0.80
1.00
1.20
1.40
1.60
Rela
tive r
isk (
95%
CI)
Stroke CHD
Active Therapy vs. Placebo
CHF Death
0.630.63
0.460.46
0.680.68
0.870.87
CVD
0.750.75
SHEP Cardiovascular Disease EndpointsSHEP Cardiovascular Disease Endpoints
SHEP Research Group. JAMA. 1991;265:3255-3264.
SHEP=Systolic Hypertension in the Elderly Program
CHD=coronary heart disease; CHF=congestive heart failure; CVD=cardiovascular disease
Hypertensiononline.org
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70
80
90
100
Su
rviv
al fr
ee o
f even
t (%
)
Year of follow-up
EWPHE Cardiovascular Mortality EWPHE Cardiovascular Mortality On-Treatment AnalysisOn-Treatment Analysis
Active (n=416)
Placebo (n=424)
P=0.023
0 1 3 62 4 5 7
Amery A, et al. Lancet. 1985;1:1349-1354.Reprinted with permission from Elsevier Science.
EWPHE=European Working Party on High Blood Pressure in the Elderly
Hypertensiononline.org
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Blood Pressure & The Very ElderlyBlood Pressure & The Very Elderly
Epidemiologic population studies suggest Epidemiologic population studies suggest better survival with higher levels of blood better survival with higher levels of blood pressurepressure
Worse survival reported in hypertensives Worse survival reported in hypertensives
with SBP levels below 140 mmHgwith SBP levels below 140 mmHg (Oates et al. (Oates et al. 2007)2007)
Meta-analysis (n=1670)Meta-analysis (n=1670) (Gueyffier et al. 1997)(Gueyffier et al. 1997) 36% reduction in the risk of stroke (BENEFIT)36% reduction in the risk of stroke (BENEFIT)14% (p=0.05) increase in total mortality (RISK)14% (p=0.05) increase in total mortality (RISK)
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The Trial:International, multi-centre, randomised double-blind placebo controlled
Inclusion Criteria: Exclusion Criteria:Aged 80 or more, Standing SBP < 140mmHgSystolic BP; 160 -199mmHg Stroke in last 6 months+ diastolic BP; <110 mmHg, DementiaInformed consent Need daily nursing care
CHF or Cr more than 1.7Primary Endpoint: All strokes (fatal and non-fatal)
Target blood pressure
150/80 mmHg
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All stroke(30% reduction)
PlaceboIndapamideSR ±perindopril
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Heart Failure(64% reduction)
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Total Mortality(21% reduction)
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ConclusionsConclusions
Antihypertensive treatment based on indapamide ± Antihypertensive treatment based on indapamide ± perindopril reduced stroke mortality and total perindopril reduced stroke mortality and total mortality in a very elderly cohort.mortality in a very elderly cohort.
NNT (2 years) = 94 for stroke and 40 for mortalityNNT (2 years) = 94 for stroke and 40 for mortality
Large and significant benefit in reduction of heart Large and significant benefit in reduction of heart failure events and for combined endpoint of failure events and for combined endpoint of cardiovascular eventscardiovascular events
Goal blood pressure was 150/80Goal blood pressure was 150/80
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INVEST Trial Secondary analysisINVEST Trial Secondary analysis
The risk for the The risk for the primary endpoint primary endpoint (death, myocardial (death, myocardial infarction, or stroke) infarction, or stroke) progressively progressively increased with low increased with low diastolic blood diastolic blood pressure.pressure.
AIM 144:884 (2006)
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ConclusionsConclusions
Evidence supports moderate blood Evidence supports moderate blood pressure reduction in the very elderly to pressure reduction in the very elderly to goal of 150/80goal of 150/80
Excessive reduction of diastolic pressure Excessive reduction of diastolic pressure may have adverse consequences may have adverse consequences
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My PatientMy Patient
Target blood pressure of 150/80Target blood pressure of 150/80Achieve goal with low dose thiazide diurecticAchieve goal with low dose thiazide diurectic
Consider ACE-I or CCB for combination Consider ACE-I or CCB for combination therapytherapy
Monitor home blood pressuresMonitor home blood pressuresConsider titrating to standing blood pressureConsider titrating to standing blood pressure
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Question #2Question #2
Is combination therapy with an Is combination therapy with an angiotensin-converting enzyme inhibitor angiotensin-converting enzyme inhibitor (ACE) and an angiotensin receptor blocker (ACE) and an angiotensin receptor blocker (ARB) appropriate for my patient with (ARB) appropriate for my patient with essential hypertension requiring an essential hypertension requiring an additional agent to reach goal?additional agent to reach goal?
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Renin-Angiotensin PathwayRenin-Angiotensin Pathway
www.kidney.org
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Practice TrendsPractice Trends
Since 2000, several trials compared dual Since 2000, several trials compared dual ACE-ARB therapy in nephropathy and ACE-ARB therapy in nephropathy and coronary disease coronary disease COOPERATE, CHARM, VALLIANT, COOPERATE, CHARM, VALLIANT,
ONTAGERT ONTAGERT
General thought: More blockade must be General thought: More blockade must be betterbetter
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COOPERATECOOPERATE
Evaluated combination of losartan and Evaluated combination of losartan and trandolapril in non-diabetic proteinuric trandolapril in non-diabetic proteinuric renal diseaserenal disease
Significant benefit from combination Significant benefit from combination therapy in slowing progression of diseasetherapy in slowing progression of disease
Publication retracted by the Lancet in Publication retracted by the Lancet in October 2009October 2009
Lancet 2003 Jan 11;361(9352):117-24 Lancet 2009 Oct 9;374(9697):1226
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ACE and ARB medications equally reduce ACE and ARB medications equally reduce proteinuriaproteinuria
Combination therapy has greater effectCombination therapy has greater effect
Unable to assess outcomesUnable to assess outcomes
Ann Intern Med. 2008 Jan 1;148(1):30-48
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Effects of telmisartan, ramipril, or both on Effects of telmisartan, ramipril, or both on death from cardiovascular causes, MI, death from cardiovascular causes, MI, stroke, or hospitalization for heart failurestroke, or hospitalization for heart failure
No No significant difference in primary significant difference in primary outcomes between any armsoutcomes between any arms
ONTARGETONTARGET
NEJM 2008; 358:1547-1559NEJM 2008; 358:1547-1559
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ONTARGET Dual TherapyONTARGET Dual Therapy
Average BP reduction of 2-3 mmHg in Average BP reduction of 2-3 mmHg in combination armcombination armExpected 4-5% reduction in primary outcome Expected 4-5% reduction in primary outcome
not foundnot foundSignificant increases in:Significant increases in:
HypotensionHypotensionHyperkalemiaHyperkalemiaRenal dysfunctionRenal dysfunctionSyncope Syncope
NEJM 2008; 358: 1547-1559NEJM 2008; 358: 1547-1559
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ONTARGET ConclusionsONTARGET Conclusions
Patients who have vascular disease or Patients who have vascular disease or high risk diabetes, telmisartan is not high risk diabetes, telmisartan is not inferior to ramiprilinferior to ramipril
No additional benefit from combination No additional benefit from combination therapytherapySignificantly more riskSignificantly more riskBP reduction not beneficialBP reduction not beneficial
NEJM 2008; 358: 1547-1559NEJM 2008; 358: 1547-1559
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My PatientMy Patient
ACE or ARB is appropriateACE or ARB is appropriate
Combination therapy not routinely Combination therapy not routinely indicated for blood pressure reductionindicated for blood pressure reductionSpecific populations may have benefit from Specific populations may have benefit from
combination therapy combination therapy Consider other options for proteinuria Consider other options for proteinuria
reduction if indicatedreduction if indicated
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Question #3Question #3
I have a 50 year-old male patient with I have a 50 year-old male patient with elevated systolic blood pressures over 160 elevated systolic blood pressures over 160 mmHg at every clinic visit. His home mmHg at every clinic visit. His home blood pressure is always less than 130 blood pressure is always less than 130 mmHg.mmHg.
What is his cardiovascular risk from his What is his cardiovascular risk from his elevated clinic readings?elevated clinic readings?
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Blood Pressure Response to Physician or Nurse
0
5
10
15
20
25
Peak 5 Minutes 10 Minutes
Time
Sy
sto
lic
Ch
an
ge
fro
m B
as
eli
ne
(m
mH
g)
Physician
Nurse
Hypertension 1987;9:209
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White Coat HypertensionWhite Coat Hypertension
Definition:Definition:DaytimeDaytime blood pressure average less than blood pressure average less than
130/80 mmHg130/80 mmHgClinic readings greater than 140/90 mmHgClinic readings greater than 140/90 mmHg
White Coat EffectWhite Coat EffectElevated pressure in the clinic superimposed Elevated pressure in the clinic superimposed
on essential hypertensionon essential hypertension
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Scope of the ProblemScope of the Problem
Prevalence range 10 – 30% of patients Prevalence range 10 – 30% of patients with clinical hypertensionwith clinical hypertensionDiagnosis of hypertension usually made on Diagnosis of hypertension usually made on
clinic blood pressure recordingsclinic blood pressure recordings10% - 74% will progress to hypertension over 10% - 74% will progress to hypertension over
5 years5 years
Historically considered a benign conditionHistorically considered a benign condition
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Outcomes in White Coat Outcomes in White Coat Hypertension (WCH)Hypertension (WCH)
3.2 3.7
0.8
3.7
7.9
15.3
02468
101214161820
% o
f P
atie
nts
Non CardiacDeath
CVA CoronaryEvent
WCH
SustainedHTN
P<0.001
P<0.001
NS
Khatter et al, Circulation. 1998;98:1892
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Hypertension. 2005;45:203-208
Analysis of data from 4 cohort studies in 3 Analysis of data from 4 cohort studies in 3 countriescountries
Followed for a median 5.3 yearsFollowed for a median 5.3 years
Evaluated incidence of strokeEvaluated incidence of stroke
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ResultsResults
Significant increased risk of stroke from:Significant increased risk of stroke from:Elevated office and sleep systolic pressureElevated office and sleep systolic pressureTobacco useTobacco useOlder ageOlder ageDiabetesDiabetes
No clear significant increased risk from No clear significant increased risk from white coat hypertensionwhite coat hypertension
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Six-Year Risk-Factor Adjusted Six-Year Risk-Factor Adjusted Probability of StrokeProbability of Stroke
Hypertension. 2005;45:203-208
0
2
4
6
8
Pro
bab
ilit
y
Women Men Women Men
Normotensive
WCH
HTN
Non-Smokers Smokers
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Cumulative Hazard for StrokeCumulative Hazard for Stroke
Hypertension. 2005;45:203-208
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ConclusionsConclusions
Patients with white coat hypertension are Patients with white coat hypertension are at risk for progression to hypertension, at risk for progression to hypertension, likely greater than a normotensive cohortlikely greater than a normotensive cohort
While the cardiovascular risk from WCH is While the cardiovascular risk from WCH is less than with hypertension, it may still less than with hypertension, it may still carry some riskcarry some risk
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My PatientMy Patient
Cardiac risk stratification from other risk Cardiac risk stratification from other risk factorsfactorsLifestyle modificationLifestyle modification
Low sodium dietLow sodium dietRegular exerciseRegular exercise
Occasional home blood pressure monitoringOccasional home blood pressure monitoringConsider 24 hour ambulatory blood pressure Consider 24 hour ambulatory blood pressure
monitormonitor
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ConclusionsConclusions
To meet blood pressure goals we must:To meet blood pressure goals we must:Make the diagnosis more frequentlyMake the diagnosis more frequentlyEducate our patientsEducate our patientsTreat more aggressively, with simple Treat more aggressively, with simple
medication regimensmedication regimensReassess to reach goalsReassess to reach goals
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Thank youThank you
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ResourcesResources
Amery A, et al. Amery A, et al. LancetLancet. 1985;1:1349-1354.. 1985;1:1349-1354.
Ann Med 2006; 144:884Ann Med 2006; 144:884
Burt VI, et al. Burt VI, et al. HypertensionHypertension. 1995;25:305-313.. 1995;25:305-313.
Hypertension.Hypertension. 1987;9:209 1987;9:209
HypertensionHypertension. 2005;45:203-208. 2005;45:203-208
Khatter et al; Khatter et al; CirculationCirculation. 1998;98:1892. 1998;98:1892
LancetLancet 2003;361(9352):117-24 2003;361(9352):117-24
LancetLancet 2003; 362 (9395): 2003; 362 (9395):
Ong, et al. Ong, et al. Hypertension.Hypertension. 2007 2007
SHEP Research Group. SHEP Research Group. JAMAJAMA. 1991;265:3255-3264.. 1991;265:3255-3264.