Conflict of Interest This presentation by Franz H. Messerli is sponsored by Boehringer Ingelheim. Therefore any mentioning of a Boehringer Ingelheim product

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.

““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

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 %??

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

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.

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

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 ??

• ““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 … ”

• “… “… 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

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

““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.

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.

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.

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

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

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

•

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 "

http://www.theheart.org/viewAuthorBio.do?primaryKey=113917

http://www.theheart.org/article/769007.do#bib_1

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

Antihypertensive Therapy and Antihypertensive Therapy and

CardioprotectionCardioprotection

??yesyesSecondary Secondary PreventionPrevention

yesyesnonoPrimary Primary PreventionPrevention

DiureticsDiureticsBeta Beta BlockersBlockers

"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…

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

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

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

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

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.

Effects of Telmisartan vs AmlodipineDerived from 24-h ABPM1




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


Effects of Telmisartan vs AmlodipineDerived from 24-h ABPM1




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


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

Effect of ACE-Is on BP at TroughEffect of ACE-Is on BP at Trough( placebo subtracted )( placebo subtracted )



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

Dose Response of ARB Withdrawal RateDose Response of ARB Withdrawal Rate



Dose Response of ARB Withdrawal RateDose Response of ARB Withdrawal Rate



Dose Response of ACE-I Withdrawal RateDose Response of ACE-I Withdrawal Rate


RRRR


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

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%


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


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

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


• 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


• Median time between 1Median time between 1stst attack and ACE-I Rx attack and ACE-I Rx withdrawal: 12 monthswithdrawal: 12 months


Lorenza et al. CMJ, 2006;175:1065

• 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

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

Kaplan-Meier Curves for the Primary Outcome in the Three Study Groups

The ONTARGET Investigators. N Engl J Med 2008;10.1056/NEJMoa0801317

The ONTARGET Investigators. N Engl J Med 2008;10.1056/NEJMoa0801317

Discontinuation of Study Medications and Selected Reasons for Permanent Discontinuation

1. ONTARGET establishes outcome equivalence for Ramipril and Telmisartan.

MESSERLI’s Take Home Lessons from ONTARGET, ACCOMPLISH

and HYVET

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

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

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.

NonSense of Dual RAS BlockadeNonSense of Dual RAS BlockadeNonSense of Dual RAS BlockadeNonSense of Dual RAS Blockade

• “..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…”

Mann JE, Schmieder RE et al. Lancet 2008

ONTARGET: Change in eGFR from Run-in (intention to treat analysis)

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

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Lakhdar%20R%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Lakhdar%20R%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Al-Mallah%20MH%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus



http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Lanfear%20DE%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Lanfear%20DE%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus

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

J Am Coll Cardiol, 2009; 53:468-470J Am Coll Cardiol, 2009; 53:468-470

“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

““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

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

Documents

Conflict of Interest This presentation by Franz H. Messerli is sponsored by Boehringer Ingelheim. Therefore any mentioning of a Boehringer Ingelheim product