conflict of interest this presentation by franz h. messerli is sponsored by boehringer ingelheim....
TRANSCRIPT
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Conflict of Interest
This presentation by Franz H. Messerli is sponsored by
Boehringer Ingelheim. Therefore any mentioning of a Boehringer
Ingelheim product should be considered as biased information and automatically be treated as
suspicious.
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““In the past 100 years, only In the past 100 years, only during the 1918 flu pandemic during the 1918 flu pandemic was cardiovascular disease was cardiovascular disease notnot the number-one cause of the number-one cause of
death”. death”.
AHA Year End Statistics 2005AHA Year End Statistics 2005
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What is the residual lifetime risk What is the residual lifetime risk of becoming hypertensive in a of becoming hypertensive in a
normotensive person at age 55?normotensive person at age 55?
What is the residual lifetime risk What is the residual lifetime risk of becoming hypertensive in a of becoming hypertensive in a
normotensive person at age 55?normotensive person at age 55?
• 10 – 30 %10 – 30 %
• 30 – 50 %30 – 50 %
• 50 – 70 %50 – 70 %
• 70 – 90 %70 – 90 %
• >90 %>90 %??
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Residual Lifetime Risk for Residual Lifetime Risk for Hypertension From Age 55Hypertension From Age 55Residual Lifetime Risk for Residual Lifetime Risk for Hypertension From Age 55Hypertension From Age 55
Vasan RS et al. JAMA. 2002;287:1003-1010 Framingham.
Individuals who are normotensive at age 55 have a > 90% lifetime risk of developing hypertension
Ris
k fo
r H
yper
ten
sio
n (
%)
Time (Years)10 15 20 25
0
20
40
60
80
100
52
8391
72
56
8893
78
Women
Men
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Excess Mortality in Harlem
U.S. White
Bangladesh
Harlem
0102030405060708090
100
0 5 15 25 35 45 55 65
Age (yr)
Perc
en
t A
liv
e
McCord C, Freeman HP. N Engl J Med. 1990 Jan 18;322(3):173-7.
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26.8
21.6
6.5 4.4 4.3 2.8 2.7 2.7 2.6 2.1
23.5
0
10
20
30
Black, non-Hispanic
Heartdisease
Cancer Stroke Diabetes Unintentionalinjury
Homicide Chroniclower
respiratorydisease
HIV Nephritis Septicemia All others
Cause of death
10 leading causes of death among non-Hispanic blacks and non-Hispanic whites
National Vital Statistics System, United States, 2002
29.223.1
6.7 5.7 4.1 2.8 2.7 2.6 1.5 1.3
20.2
0
10
20
30
White, non-Hispanic
Heartdisease
Cancer Stroke Chroniclower
respiratorydisease
Unintentionalinjury
Influenza andpneumonia
Altzheimer'sdisease
Diabetes Nephritis Suicide All others
Cause of death
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Month and YearMonth and Year
00
Art
eri
al B
loo
d P
res
su
re (
mm
Hg
)A
rte
ria
l Blo
od
Pre
ss
ure
(m
mH
g)
19371937 19391939 19411941 1944194419351935MM AA MM JJ JJ AA SS OO NN DD JJ FF MM AA
19451945
5050
100100
150150
200200
250250
300300
350350
Arterial Pressure of Franklin D. Roosevelt from 1935 Arterial Pressure of Franklin D. Roosevelt from 1935 until his death on April 12, 1945until his death on April 12, 1945
EKG:EKG: LVHLVH
Proteinuria:Proteinuria: ++ + ++ +
Messerli, FH, NEJM, 332:1038-1039, 1995Messerli, FH, NEJM, 332:1038-1039, 1995
D-DayD-Day ElectionElection YaltaYalta ??
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• ““The treatment of the The treatment of the hypertension itself is a hypertension itself is a difficult and almost hopeless difficult and almost hopeless task in the present state of task in the present state of our knowledge and in fact, for our knowledge and in fact, for aught we know … ”aught we know … ”
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• “… “… the hypertension may be the hypertension may be an important an important compensatorycompensatory mechanism which should not mechanism which should not be tampered with, even were be tampered with, even were it certain that we could it certain that we could control it.”control it.”
Paul Dudley White, MD,Paul Dudley White, MD,Heart Disease, Heart Disease, First Edition First Edition 19311931
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Syst-Eur: Fatal and Nonfatal Stroke Syst-Eur: Fatal and Nonfatal Stroke (in 4695 Randomized Patients)(in 4695 Randomized Patients)
PlaceboPlacebo
ActiveActiveTreatmentTreatment
-42%42%P P < 0.003< 0.003
Staessen J et al. 1997Staessen J et al. 1997 Time Since Randomization (Years)Time Since Randomization (Years)
Even
ts p
er 1
00 P
atie
nts
Even
ts p
er 1
00 P
atie
nts
6 – 6 –
5 – 5 –
4 – 4 –
3 – 3 –
2 – 2 –
1 – 1 –
0 – 0 – II00
II11
II22
II33
II44
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““Systolic hypertension in the Systolic hypertension in the presence of a normal or reduced presence of a normal or reduced diastolic pressure is rarely diastolic pressure is rarely considered responsible for target considered responsible for target organ damage.”organ damage.”
Engelman K, Braunwald E. Ch.37, “Elevation of Arterial Engelman K, Braunwald E. Ch.37, “Elevation of Arterial Blood Pressure,” Blood Pressure,” Harrison’s Principles of Internal MedicineHarrison’s Principles of Internal Medicine. . 66thth Ed. 1970. Ed. 1970.
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Syst-Eur: Fatal and Nonfatal Stroke Syst-Eur: Fatal and Nonfatal Stroke (in 4695 Randomized Patients)(in 4695 Randomized Patients)
P P < 0.001< 0.001
PP = 0.003 = 0.003
PP = 0.12 = 0.12
PP= 0.03= 0.03
- 32%- 32%
PP= 0.12= 0.12
All EndpointsAll Endpoints
StrokeStroke
CardiacCardiac
CHFCHF
MIMI
Active BetterActive Better Placebo BetterPlacebo Better
- 42%- 42%
- 26%- 26%
- 29%- 29%
- 30%- 30%
-100-100 -50-50 00 50%50%
Staessen J, et al. 1997.Staessen J, et al. 1997.
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Data Selection:Data Selection:
• Randomized trials lasting at least Randomized trials lasting at least one year, which used as first line one year, which used as first line agents diuretics and/or agents diuretics and/or betabeta--blockers and reported morbidity blockers and reported morbidity and mortality outcomes in elderly and mortality outcomes in elderly hypertensive patients.hypertensive patients.
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Meta-Analysis of Prospective Clinical Trials Meta-Analysis of Prospective Clinical Trials in Hypertension in the Elderlyin Hypertension in the Elderly
All Cause Mortality
Diuretics 7 681/5838 907/6618
ß-blockers 2 227/1521 384/2678
0.4 0.6 0.8 1.0 1.2 1.4
Active Treatment ControlOutcome Events/ Events/ Odds Ratio andFirst Drug # Trials Patient Patients 95% Confidence Interval
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Active Treatment ControlOutcome Events/ Events/ Odds Ratio andFirst Drug # Trials Patient Patients 95% Confidence Interval
0.4 0.6 0.8 1.0 1.2 1.4
Coronary Heart Disease Diuretics 8 365/5876 531/6661
ß-blockers 2 115/1521 197/2678
Cardio-Vascular Disease Diuretics 7 332/5838 510/6618
ß-blockers 2 130/1521 230/2678
Meta-Analysis of Prospective Clinical Trials Meta-Analysis of Prospective Clinical Trials in Hypertension in the Elderlyin Hypertension in the Elderly
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Carlberg B et al. Lancet 2004; 364:1684–1689.
Relative risk of major events with Relative risk of major events with atenolol vs placebo (n = 6825) atenolol vs placebo (n = 6825)
End pointEnd point RRRR 95% CI95% CI
All-cause mortalityAll-cause mortality 1.011.01 0.89-1.150.89-1.15
Cardiovascular Cardiovascular mortalitymortality
0.990.99 0.83-1.180.83-1.18
MIMI 0.990.99 0.83-1.190.83-1.19
Stroke Stroke 0.850.85 0.72-1.010.72-1.01
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•
Cochrane reviewCochrane review: Beta : Beta blockers should not be first line for blockers should not be first line for hypertensionhypertension February 2, 2007 February 2, 2007 Sue Hughes
• The available evidence does not support the use of beta blockers The available evidence does not support the use of beta blockers as first-line drugs in the treatment of hypertension [as first-line drugs in the treatment of hypertension [1].
• • The review bases this conclusion on "the relatively weak The review bases this conclusion on "the relatively weak
effect of beta blockers to reduce stroke and the absence effect of beta blockers to reduce stroke and the absence of an effect on coronary heart disease when compared of an effect on coronary heart disease when compared with placebo "with placebo "
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Analysis 01.01. Comparison 01 Beta-blocker vs Placebo or No treatment, Outcome 01 Total mortality
Cochrane Database of Systematic ReviewsPublished by John Wiley & Sons, Ltd: 24 January : 24 January
2007 2007
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Antihypertensive Therapy and Antihypertensive Therapy and
CardioprotectionCardioprotection
??yesyesSecondary Secondary PreventionPrevention
yesyesnonoPrimary Primary PreventionPrevention
DiureticsDiureticsBeta Beta BlockersBlockers
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"Which of the following class of "Which of the following class of drugs have been proven to reduce drugs have been proven to reduce mortality in hypertensive patients?"mortality in hypertensive patients?"
• Beta-blockers 78%Beta-blockers 78%
• ACE inhibitors 65%ACE inhibitors 65%
• Diuretics 53%Diuretics 53%
• CCBs 17%CCBs 17%
Kaboli PJ, et al. J Clin Hypertens 2007;9:416-423. Kaboli PJ, et al. J Clin Hypertens 2007;9:416-423.
Myths and Misperceptions…Myths and Misperceptions…
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00
22
44
66
88
1010
00 44 6622 88
SYST EUR: Effect of Calcium Antagonist SYST EUR: Effect of Calcium Antagonist Treatment on DementiaTreatment on Dementia
Time since Randomization (Years)Time since Randomization (Years)
Cas
es p
er 1
00 P
atie
nts
Cas
es p
er 1
00 P
atie
nts
Forette F., et al.Forette F., et al.
Arch Intern MedArch Intern Med
In Press 2002In Press 2002
Active Active TreatmentTreatment
PlaceboPlacebo
-55%-55%P=0.0008P=0.0008
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Effect of Antihypertensive Effect of Antihypertensive Therapy on Cognitive Therapy on Cognitive Dysfunction/DementiaDysfunction/Dementia
Forette F, et al. Lancet. 1998;352(9137):1347-51.
StudyStudy SHEPSHEP SYST-EURSYST-EUR
RXRX Thiazide Thiazide DiureticDiuretic
Calcium Calcium antagonistantagonist
EffectEffect NoneNone 55%55% ReductionReduction
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Outcome Evidence for Outcome Evidence for Betablockers in CV DiseaseBetablockers in CV Disease
Outcome Evidence for Outcome Evidence for Betablockers in CV DiseaseBetablockers in CV Disease
++++
++
++
++
++
++
Hypertension
Heart Failure
ACS
Post MI
Stable Angina
HOCM
Perioperative
None Some Strong
Bangalore S, Messerli FH et al. JACC in press Bangalore S, Messerli FH et al. JACC in press 20072007
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Percentage of Patients Continuing Percentage of Patients Continuing Prescribed Drug Regimen after 1 YearPrescribed Drug Regimen after 1 Year
Per
cen
tP
erce
nt
100100
8080
6060
4040
2020
00 ARBARB ACEIACEI CACA DD BBBB
Mancia G, et al. AJH 2003;16:1066–73
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Telmisartan vs Amlodipine Using 24-h ABPM1
PlaceboPlacebo(n = 58)(n = 58)
TelmisartanTelmisartan(40–120 mg)(40–120 mg)(n = 62)(n = 62)
AmlodipineAmlodipine(5–10 mg)(5–10 mg)(n = 65)(n = 65)
00
8080
100100
120120
140140
160160
DBPDBP
SBPSBP
1200120008000800 20002000 24002400 04000400 0800080016001600
Time of DayTime of Day
BP
(m
m H
g)
BP
(m
m H
g)
Baseline ABPMBaseline ABPM
1. Lacourci1. Lacourcièère Y, Lenis J, Orchard R, et al. A comparison of the efficacy and duration of action of there Y, Lenis J, Orchard R, et al. A comparison of the efficacy and duration of action of theangiotensin II receptor blocker telmisartan to amlodipine. angiotensin II receptor blocker telmisartan to amlodipine. Blood Press Monit. Blood Press Monit. 1998;3:295–302.1998;3:295–302.
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Effects of Telmisartan vs AmlodipineDerived from 24-h ABPM1
PlaceboPlacebo(n = 58)(n = 58)
TelmisartanTelmisartan(40–120 mg)(40–120 mg)(n = 62)(n = 62)
AmlodipineAmlodipine(5–10 mg)(5–10 mg)(n = 65)(n = 65)
140140
160160
1200120008000800 20002000 24002400 04000400 0800080016001600
Time of DayTime of Day
BP
(m
m H
g)
BP
(m
m H
g)
120120
150150
130130
End of Therapy (Week 12) – Systolic BPEnd of Therapy (Week 12) – Systolic BP
1. Lacourci1. Lacourcièère Y, Lenis J, Orchard R, et al. A comparison of the efficacy and duration of action of there Y, Lenis J, Orchard R, et al. A comparison of the efficacy and duration of action of theangiotensin II receptor blocker telmisartan to amlodipine. angiotensin II receptor blocker telmisartan to amlodipine. Blood Press Monit. Blood Press Monit. 1998;3:295–302.1998;3:295–302.
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Effects of Telmisartan vs AmlodipineDerived from 24-h ABPM1
PlaceboPlacebo(n = 58)(n = 58)
TelmisartanTelmisartan(40–120 mg)(40–120 mg)(n = 62)(n = 62)
AmlodipineAmlodipine(5–10 mg)(5–10 mg)(n = 65)(n = 65)
TimeTime
BP
(m
m H
g)
BP
(m
m H
g)
110110
1200120008000800 20002000 24002400 04000400 08000800160016006060
100100
9090
8080
7070
End of Therapy (Week 12) – Diastolic BPEnd of Therapy (Week 12) – Diastolic BP
1. Lacourci1. Lacourcièère Y, Lenis J, Orchard R, et al. A comparison of the efficacy and duration of action of there Y, Lenis J, Orchard R, et al. A comparison of the efficacy and duration of action of theangiotensin II receptor blocker telmisartan to amlodipine. angiotensin II receptor blocker telmisartan to amlodipine. Blood Press Monit. Blood Press Monit. 1998;3:295–302.1998;3:295–302.
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Effect of ARBs on BP at TroughEffect of ARBs on BP at Trough( placebo subtracted )( placebo subtracted )
46 studies, 13451 pts46 studies, 13451 pts
The Cochrane Collaboration, The Cochrane Collaboration, Heran BS et al. October 2008Heran BS et al. October 2008
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Effect of ACE-Is on BP at TroughEffect of ACE-Is on BP at Trough( placebo subtracted )( placebo subtracted )
The Cochrane Collaboration, The Cochrane Collaboration, Heran BS et al. October 2008Heran BS et al. October 2008
92 studies, 12954 pts92 studies, 12954 pts
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Blood Pressure Reduction at Trough
-10-9-8-7-6-5-4-3-2-10
ACEinhibitors
ARBs DRIs
Systolic
Diastolic
mm Hg
# of Studies 92 46 6
# of Patients 12954 13451 3694
# of Drugs 14 9 11
Messerli FH, Bangalore S. Circulation. 2009;119(3):371-3Messerli FH, Bangalore S. Circulation. 2009;119(3):371-3
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Dose Response of ARB Withdrawal RateDose Response of ARB Withdrawal Rate
The Cochrane Collaboration, The Cochrane Collaboration, Heran BS et al. October 2008Heran BS et al. October 2008
46 studies, 13451 pts46 studies, 13451 pts
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Dose Response of ARB Withdrawal RateDose Response of ARB Withdrawal Rate
The Cochrane Collaboration, The Cochrane Collaboration, Heran BS et al. October 2008Heran BS et al. October 2008
46 studies, 13451 pts46 studies, 13451 pts
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Dose Response of ACE-I Withdrawal RateDose Response of ACE-I Withdrawal Rate
92 studies, 12954 pts92 studies, 12954 pts
RRRR
The Cochrane Collaboration, The Cochrane Collaboration, Heran BS et al. October 2008Heran BS et al. October 2008
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ACE-Inhibitor Related Angioedema –ACE-Inhibitor Related Angioedema –How Uncommon?How Uncommon?
ACE-Inhibitor Related Angioedema –ACE-Inhibitor Related Angioedema –How Uncommon?How Uncommon?
Incidence: Incidence: 0. 1%0. 1% 0. 2% 0. 5%0. 5%
First week incidence 1/2,500 pts.First week incidence 1/2,500 pts.
Subsequent incidence Subsequent incidence 1/500 pts/year
Incidence: Incidence: 0. 1%0. 1% 0. 2% 0. 5%0. 5%
First week incidence 1/2,500 pts.First week incidence 1/2,500 pts.
Subsequent incidence Subsequent incidence 1/500 pts/year
Messerli FH, Nussberger. Lancet 2000;356:608–9
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The Risk of Angioedema (AE)The Risk of Angioedema (AE)The Risk of Angioedema (AE)The Risk of Angioedema (AE)
• Among angioedema thatAmong angioedema thatare life-threateningare life-threatening(larynx, respiratory tract):(larynx, respiratory tract): 20 – 22%20 – 22%
• Among life-threateningAmong life-threateningangioedema thatangioedema thatare fatal:are fatal: 1 – 1 – 16 – – 24%24%
• Among angioedema thatAmong angioedema thatare life-threateningare life-threatening(larynx, respiratory tract):(larynx, respiratory tract): 20 – 22%20 – 22%
• Among life-threateningAmong life-threateningangioedema thatangioedema thatare fatal:are fatal: 1 – 1 – 16 – – 24%24%
Messerli FH, Nussberger. Lancet 2000;356:608–9
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ACE-Inhibitors and Angioedema (AE)ACE-Inhibitors and Angioedema (AE)ACE-Inhibitors and Angioedema (AE)ACE-Inhibitors and Angioedema (AE)
Worldwide ACE-I useWorldwide ACE-I use > 30,000,000> 30,000,000
Episodes of Angioedema/yearEpisodes of Angioedema/year 60,00060,000
Episodes of life-threatening Episodes of life-threatening
Angioedema/yearAngioedema/year 12,00012,000
Episodes of fatal Episodes of fatal
Angioedema/yearAngioedema/year >1,000
Worldwide ACE-I useWorldwide ACE-I use > 30,000,000> 30,000,000
Episodes of Angioedema/yearEpisodes of Angioedema/year 60,00060,000
Episodes of life-threatening Episodes of life-threatening
Angioedema/yearAngioedema/year 12,00012,000
Episodes of fatal Episodes of fatal
Angioedema/yearAngioedema/year >1,000
Number of patientsNumber of patients
Messerli FH, Nussberger. Lancet 2000;356:608–9
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Asphyxia Due to ACE Inhibitor Mediated AngioedemaAsphyxia Due to ACE Inhibitor Mediated AngioedemaAsphyxia Due to ACE Inhibitor Mediated AngioedemaAsphyxia Due to ACE Inhibitor Mediated Angioedema
Dean DE, et al. J Forensic Science 2001;46:1239–43
Age Sex Race Diagnosis ACE InhibitorDuration of Exposure Angioedema
5656 FF AAAA HTN, DM, CHFHTN, DM, CHF fosinoprilfosinopril 5 months5 months TongueTongue
5151 FF AAAA HTN, DM, CHFHTN, DM, CHF benazeprilbenazepril 21 months21 months Tongue, LipsTongue, Lips
6363 MM AAAA HTNHTN enalaprilenalapril 8 month8 month Tongue, Tongue, Oropharynx, Oropharynx, Hypopharynx, Hypopharynx, LarynxLarynx
5454 MM AAAA HTN Nephr. HTN Nephr. Syn.Syn.
lisinoprillisinopril 10 hours10 hours Tongue, Tongue, OropharynxOropharynx
6565 MM AAAA HTNHTN enalaprilenalapril chronicchronic Tongue, LarynxTongue, Larynx
7171 FF AAAA HTNHTN lisinoprillisinopril chronicchronic Tongue, LarynxTongue, Larynx
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Angioedema with ACE-InhibitorsAngioedema with ACE-Inhibitors
• n = 85n = 85
• Rx for hypertension n = 82Rx for hypertension n = 82
• Rx for heart failure n = 3Rx for heart failure n = 3
• Median duration of ACE-I Rx: Median duration of ACE-I Rx: 12 months
• Range: 1 day – 13 yearsRange: 1 day – 13 years
• Median time between 1Median time between 1stst attack and ACE-I Rx attack and ACE-I Rx withdrawal: 12 monthswithdrawal: 12 months
• Range: 1 day – 12 yearsRange: 1 day – 12 years
• n = 85n = 85
• Rx for hypertension n = 82Rx for hypertension n = 82
• Rx for heart failure n = 3Rx for heart failure n = 3
• Median duration of ACE-I Rx: Median duration of ACE-I Rx: 12 months
• Range: 1 day – 13 yearsRange: 1 day – 13 years
• Median time between 1Median time between 1stst attack and ACE-I Rx attack and ACE-I Rx withdrawal: 12 monthswithdrawal: 12 months
• Range: 1 day – 12 yearsRange: 1 day – 12 years
Lorenza et al. CMJ, 2006;175:1065
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• Losartan (%) Atenolol (%) p-value
•Angioedema 6 (0∙1%) 11 (0∙2%) 0∙237
•Bradycardia 66 (1%) 391 (9%) <0∙0001
•Cancer 356 (8%) 315 (7%) 0∙118
•Cold extremities 178 (4%) 269 (6%) <0∙0001
•Cough 133 (3%) 113 (2%) 0∙220
•Dizziness 771 (17%) 727 (16%) 0∙247
•Hypotension 121 (3%) 75 (2%) 0∙001
•Sexual dysfunction 164 (4%) 214 (5%) 0∙009
•Sleep disturbance 30 (0∙7%) 38 (0∙8%) 0∙333
LIFE: Prespecified Adverse Events of Special Interest
B Dahlof et al. Lancet 2002;359:995-1003
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VALUEVALUE:: Incidence of Incidence of angioedema and facial edemaangioedema and facial edema
Valsartan Valsartan n=7,622n=7,622
Amlodipine Amlodipine n=7,576n=7,576 p-valuep-value
AngioedemaAngioedema 10 (0∙13%)10 (0∙13%) 10 (0.13%)10 (0.13%) NSNS
Face edemaFace edema 13 (0.17%)13 (0.17%) 24 (0.32%)24 (0.32%) NSNS
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Kaplan-Meier Curves for the Primary Outcome in the Three Study Groups
The ONTARGET Investigators. N Engl J Med 2008;10.1056/NEJMoa0801317
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The ONTARGET Investigators. N Engl J Med 2008;10.1056/NEJMoa0801317
Discontinuation of Study Medications and Selected Reasons for Permanent Discontinuation
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1. ONTARGET establishes outcome equivalence for Ramipril and Telmisartan.
MESSERLI’s Take Home Lessons from ONTARGET, ACCOMPLISH
and HYVET
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1. ONTARGET establishes outcome equivalence for Ramipril and Telmisartan.
2. Outcome equivalence seems likely (but not proven) for ARBs and ACEI as a class.
MESSERLI’s Take Home Lessons from ONTARGET, ACCOMPLISH
and HYVET
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Dual Blockade of the RAS Addition of ARB to Maximal Recommended Dose
of ACEI
Mean age = 42 y; mean duration of diabetic nephropathy = 13 y.*Nephropathy defined as persistent albuminuria >300 mg/24 h.ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blocker; RAS = renin-angiotensin system.Jacobsen P et al. Kidney Int. 2003;63:1874-1880.
Double-blind, randomized, crossover trial
24 patientsType 1 diabetics with
nephropathy*
Irbesartan 300 mg/d Irbesartan 300 mg/d
Placebo Placebo
Day 1 Week 8 Week 16
Measurements:• Primary end point: albuminuria• Secondary end points:
− glomerular filtration rate (GFR)− 24-hour blood pressure
40 mg of enalapril for >3 months
R
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Addition of ARB to MaximumRecommended Dose of ACEI
0
200
400
600
Placebo + Enalapril 40 mg/d
Irbesartan 300 mg/d + Enalapril 40 mg/d
25% Reduction(P<.001)
Alb
um
inu
ria
(mg
/24
hr)
Mean reductions in 24-hour blood pressure: irbesartan + enalapril (-8/-4 mm Hg) over placebo + enalapril, (P=.002 and P=.003, respectively, for SBP and DBP). ACEI = angiotensin-converting enzyme inhibitor.Jacobsen P et al. Kidney Int. . 2003;63:1874-1880.2003;63:1874-1880.
After 8 Weeks of Therapy
AVAPRO backup slide.
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NonSense of Dual RAS BlockadeNonSense of Dual RAS BlockadeNonSense of Dual RAS BlockadeNonSense of Dual RAS Blockade
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• “..a combination of ACE inhibitor and ARB should not be used in the ONTARGET type of population. There was a strong trend in ONTARGET toward more dialysis in patients in the combination group, and other side effects were also increased…”
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Mann JE, Schmieder RE et al. Lancet 2008
ONTARGET: Change in eGFR from Run-in (intention to treat analysis)
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Safety and tolerability of ACE inhibitor versus the combination of ACE inhibitor and ARB in LV dysfunction: a systematic review and meta-analysis of randomized controlled trials.
Lakhdar R, Al-Mallah MH, Lanfear DE.
Division of Cardiology, Yale University School of Medicine
J Card Fail. 2008 Apr;14(3):181-8J Card Fail. 2008 Apr;14(3):181-8
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RESULTS: Nine trials that enrolled 18,160 patients met the inclusion criteria
• CONCLUSION:
• The current cumulative evidence suggests that patients with LVD have an increased risk of adverse events... This excess risk, coupled with a lack of mortality benefit, suggests that ARBs should not routinely be added to ACEI therapy in LVD.
J Card Fail. 2008 Apr;14(3):181-8J Card Fail. 2008 Apr;14(3):181-8
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J Am Coll Cardiol, 2009; 53:468-470J Am Coll Cardiol, 2009; 53:468-470
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“Unless data emerge to the contrary, dual RAS blockade is dead until proven otherwise…
Messerli FH, J Am Coll Cardiol, 2009; 53:468-470Messerli FH, J Am Coll Cardiol, 2009; 53:468-470
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““The treatment of the hypertension The treatment of the hypertension continues to be a difficult task in continues to be a difficult task in the present stage of our the present stage of our knowledge, but important studies knowledge, but important studies in progress offer much hope for in progress offer much hope for the future.”the future.”
Paul Dudley White, MD,Paul Dudley White, MD,Heart Disease, Heart Disease, Third Edition Third Edition 19441944
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Columbia UniversityColumbia UniversitySt. Luke’s Roosevelt HospitalSt. Luke’s Roosevelt HospitalDivision of CardiologyDivision of Cardiology
Columbia UniversityColumbia UniversitySt. Luke’s Roosevelt HospitalSt. Luke’s Roosevelt HospitalDivision of CardiologyDivision of Cardiology
FranzFranz H. Messerli, MDFranzFranz H. Messerli, MD