HEART FAILURE & Co.
This presentation is the property of its rightful owner.
Sponsored Links
1 / 26

HEART FAILURE & Co. Ninth International Symposium Milano, 17 – 18 aprile 2009 PowerPoint PPT Presentation


  • 59 Views
  • Uploaded on
  • Presentation posted in: General

HEART FAILURE & Co. Ninth International Symposium Milano, 17 – 18 aprile 2009. IL BLOCCO DEL SISTEMA RAAS NEL CONTINUUM CARDIOVASCOLARE DOPO TRENT’ANNI DI ESPERIENZATERAPEUTICA: NON SOLO ROSE E FIORI I sartani non sono inferiori ed insieme possono fare meglio Pasquale Perrone Filardi

Download Presentation

HEART FAILURE & Co. Ninth International Symposium Milano, 17 – 18 aprile 2009

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Heart failure co ninth international symposium milano 17 18 aprile 2009

HEART FAILURE & Co.

Ninth International Symposium

Milano, 17 – 18 aprile 2009

IL BLOCCO DEL SISTEMA RAAS NEL CONTINUUM CARDIOVASCOLARE DOPO TRENT’ANNI DI ESPERIENZATERAPEUTICA: NON SOLO ROSE E FIORI

I sartani non sono inferiori ed insieme possono fare meglio

Pasquale Perrone Filardi

Università Federico II di Napoli


Heart failure co ninth international symposium milano 17 18 aprile 2009

ARBs, morbidity and mortality along the cardiovascular continuum

OPTIMAAL

VALIANT

ELITE II

Val-HeFT

CHARM

LIFE

ONTARGET

TRANSCEND

Ventricular

dilation

Remodeling

DIRECT

Congestive

heart failure

Myocardial

infarction

End-stage micro-vascular and

heart disease

Atherosclerosis

and LVH

NAVIGATOR

RENAAL

IDNT

IRMA-2

MARVAL

Risk factors

Diabetes

Hypertension

Death

VALUE

SCOPE

Adapted from Dzau V, Braunwald E. Am Heart J 1991; 121: 1244–1263


Heart failure co ninth international symposium milano 17 18 aprile 2009

BIOLOGICAL EFFECTS OF RAS

 Bradykinin

Angiotensin I

ACE Inhibitors

Angiotensin II Escape

(Chymase, Cathepsin G, CAGE)

Kininase II

( - )

Inactive Fragments

Angiotensin II

NO, PGI2, HPF

t-PA

B2 Receptor

AT-II

AT-I

Natriuresis, Vasodilation

&

Anti-Inflammatory Effects

Dephosphorylation

Anti-Proliferative Effects

Phosphorylation

CNS Stimulation

Endothelin release

Vasoconstriction

NADPH Oxidase

Inflammation

Aldosteron

Proliferative Effects


Questions

QUESTIONS

  • ROLE OF ARBs IN CARDIOVASCUAR PROTECTION

  • ROLE OF DUAL RAS BLOCKADE IN CARDIOVASCULAR PROTECTION

    TARGET ORGANS

  • HEART

    • Patients at high cardiovascular risk without LV dysfunction

    • Post-MI ischemic dysfunction

    • Patients with chronic LV systolic dysfunction

    • Patients with chronic LV diastolic dysfunction

  • KIDNEY

  • EYE

  • BRAIN


Heart failure co ninth international symposium milano 17 18 aprile 2009

The ONTARGET Trial ProgrammeOutcome:Primario: mortalità CV , IMA, Ictus, ospedalizzazione per scompenso cardiacoSecondario: mortalità CV , IMA, Ictus (outcome HOPE)

ONTARGET

TRANSCEND

NO PLACEBO

YES PLACEBO

Screening

Randomisation (n= 6,000) †

Randomisation (n=23,400) *

Because of an extraordinary effort by investigators in 40 countries, it was possible to complete recruitment for the ONTARGET study in May 2003, seven months ahead of the scheduled timeline.

The ONTARGET trial currently recruited 25,621 patients.

n = 7,800Telmisartan80 mg/day +placebo

n = 7,800Ramipril10 mg/day +placebo

n = 7,800Telmisartan80 mg/day +

Ramipril10mg/day

n = 3,000Telmisartan80 mg/day

n = 3,000Placebo

5.5 Years

Follow-up at 6 weeks

Follow-up at 6 weeks

Follow-up at 6 months for 5.5 years

Follow-up at 6 months for 5.5 years

*planned. Actual = 25,620

†planned. Actual = 5,926

Teo K., et al. Am Heart J 2004;148:52–61


Tempo al primary outcome

Tempo al Primary Outcome

ONTARGET

# at Risk

Yr 1

Yr 2

Yr 3

Yr 4

T

8542

8176

7778

7420

7051

0.25

R

8576

8214

7832

7473

7095

0.20

IS RAS INHIBITION STILL USEFUL IN CONTEMPORARY PATIENTS AT HIGH CARDIOVASCULAR RISK?

0.15

Telmisartan

Cumulative Hazard Rates

Ramipril

0.10

0.05

0.0

0

1

2

3

4

Years of Follow-up


Heart failure co ninth international symposium milano 17 18 aprile 2009

TRANSCEND patients on “2008 standard care, so called placebo arm”, were almost as protected as with ramipril in HOPE

-17% absolute risk reduction

17,8%

14,8%

14%

13%

The Lancet, published on line Aug 31, 2008

N Engl J Med 2000;342:145-53


Transcend primary and key secondary outcomes

TRANSCENDPrimary and Key Secondary Outcomes


Heart failure co ninth international symposium milano 17 18 aprile 2009

Cumulative Hazard Rates

Years of Follow-up

Tempo al Primary Outcome

ONTARGET

# at Risk

Yr 1

Yr 2

Yr 3

Yr 4

0.25

8576

8214

7832

7473

7095

R

8502

8134

7740

7377

7023

T&R

0.20

0.15

Ramipril

0.10

Telmi & Ram

0.05

0.0

0

1

2

3

4


Modifiche della pa mmhg ontarget e hope

Modifiche della PA (mmHg)ONTARGET e HOPE


Heart failure co ninth international symposium milano 17 18 aprile 2009

Dogma Disputed: Can Agressively Lowering Blood Pressure in Hypertensive Patients with Coronary Artery Disease Be Dangerous?

Messerli et al Ann Intern Med 2006


Heart failure co ninth international symposium milano 17 18 aprile 2009

  • ARBs AND DUAL RAS BLOCKADE IN LEFT VENTRICULAR SYSTOLIC DYSFUNCTION

    • Post-ischemic (OPTIMA; VALIANT)

    • Chronic (VAL-HeFT; CHARM)


Heart failure co ninth international symposium milano 17 18 aprile 2009

VALSARTAN, CAPTOPRIL, OR BOTH IN MYOCARDIAL INFARCTION COMPLICATED BY HEART FAILURE, LV DYSFUNCTION OR BOTH

Pfeffer et al for the VALIANT Investigators. N Engl J Med 2003

0.4

Valsartan

Valsartan and Captopril

Captopril

n=14808

f.u. 24.7 m

0.3

0.2

Probability of Event

0.1

p = n.s. for all comparisons

0.0

0

6

12

18

24

30

36

No.at Risk

Months

Valsartan 4909 4464 4272 4007 2648 1437 357

Valsartan and Captopril 4885 4414 4265 3994 2648 1435 382

Captopril 4909 4428 4241 4018 2635 1432 364


Charm overall all cause death

CHARM-Overall All-cause death

%

35

30

945 (24.9%)

Placebo

25

886 (23.3%)

20

Candesartan

15

-9%( p=0,055)

10

HR 0.91 (95% CI 0.83-1.00), p=0.055

Adjusted HR 0.90, p=0.032

5

0

0

1

2

3

3.5

years

ANNUAL MORTALITY: 8.8 % (PL) VS 8.1 % (CANDESARTAN)


Charm overall cv death and non cv death

CHARM-Overall: CV Death and non-CV Death

CV death

HR 0.88 (95% CI 0.79-0.97), p=0.012Adjusted HR 0.87, p=0.006

30

25

Placebo

20

Candesartan

%

15

10

Non-CV death

p=0.45

Candesartan

5

Placebo

0

0

1

2

3

3.5

years

Number at risk

Candesartan 3803

Placebo 3796

Lancet. September 6, 2003


Charm effects on mortality in pts with reduced ef alternative added

CHARM: EFFECTS ON MORTALITY IN PTS WITH REDUCED EF(Alternative + Added)

40

35

30

25

All-cause death (%)

20

15

10

5

0

0

1

2

3

3.5

anni

Placebo

708 (31.0%)

Candesartan

642 (28.0%)

HR 0.88 (95% CI 0.79 – 0.98)

p=0.018

Young et al Circulation 2004; 110: 2618-26


Charm alternative primary outcome cv death or chf hospitalisation

CHARM-Alternative: Primary outcome CV death or CHF hospitalisation

%

50

406 (40.0%)

Placebo

40

334 (33.0%)

30

Candesartan

20

-23%( p=0,0004)

10

HR 0.77 (95% CI 0.67-0.89), p=0.0004Adjusted HR 0.70, p<0.0001

0

0

1

2

3

3.5

years


Most recent and upcoming randomized clinical trials in heart failure

MOST RECENT AND UPCOMING RANDOMIZED CLINICAL TRIALS IN HEART FAILURE

  • TRIALINTERVENTIONRESULTSYEAR

  • PEP-CHFperindoprilNEUTRAL2006

  • EVERESTtolvaptanNEUTRAL2007

  • CORONArosuvastatinNEUTRAL2008

  • ACCLAIMimmunomodulationNEUTRAL2008

  • AnemiadarbopoetinNEUTRAL2008

  • AFCHFrhytm vs rate controlNEUTRAL2008

  • DSGdronaderoneNEUTRAL2008

  • BEAUTIFULivabradineNEUTRAL2008

  • GISSI-HFrosuvastatin, omega-3NEUTRAL2008

  • I-PRESERVEirbesartanNEUTRAL2008

  • EMPHASISeplerenoneongoing

  • TOPCATanti-aldosteroneongoing

  • RED-HFdarbopoetinongoing


Heart failure co ninth international symposium milano 17 18 aprile 2009

  • ACE-Is, ARBs AND DUAL RAS BLOCKADE IN LEFVT VENTRICULAR DIASTOLIC DYSFUNCTION

  • ACE-Is(PEP-CHF)

  • ARBs(I-PRESERVE; CHARM PRESERVED)

  • Dual blockade (no studies)


Heart failure co ninth international symposium milano 17 18 aprile 2009

Left ventricular morphology and function in patients with heart failure with reduced or normal ejection fraction

Maeder et al. Journal of the American College of Cardiology 2009;53: 905-918


Heart failure co ninth international symposium milano 17 18 aprile 2009

EFFECTS OF PERINDOPRIL IN ELDERLY PEOPLE WITH DIASTOLIC HEART FAILURE

Cleland et al for the PEP-CHF Investigators Eur Heart J 2006; 27: 2338–2345


Heart failure co ninth international symposium milano 17 18 aprile 2009

Irbesartan in Patients with Heart Failure

and Preserved Ejection Fraction

I-PRESERVE N Engl J Med 2008;359:2456-67

Death or hospitalization for cardiovascular causes


Heart failure co ninth international symposium milano 17 18 aprile 2009

Angiotensin Receptor Antagonists Trials Across The Whole Spectrum Of Type 2 Diabetic Renal Disease Progression

Prevention

Protection

Microalbuminuria

Proteinuria

ESRD

Cardiovascular morbidity and mortality

Early Stage

Late Stage

End Stage

IRMA 2

MARVAL

IDNT

RENAAL

IRMA 2:Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria

MARVAL: Microalbuminuria Reduction with Valsartan

IDNT:Irbesartan Diabetic Nephropathy Trial

RENAAL: Reduction of Endpoints in NIDDM with the Angiotensin II Receptor Antagonist Losartan

ESRD:End-stage renal disease


Heart failure co ninth international symposium milano 17 18 aprile 2009

Effects of ramipril, telmisartan or both on renal outcomes (dialysis, doubling of serum creatinine, and death) in theONTARGETtrial

Mann et al. The Lancet 2008; 372: 547-553


Direct protect 2 retinopathy regression

DIRECT-Protect 2: Retinopathy regression

0.4

Placebo

Candesartan

0.3

0.2

Cumulative proportion

0.1

p=0.009

0.0

0

1

2

3

4

5

6

Time from randomisation (years)

No at risk

Placebo954812760713510931

Candesartan 9518117556924921000


Conclusions

CONCLUSIONS

  • ARBs (telmisartan) have demonstrated to be as efficacious as ACE-Is in patients at high cardiovascular risk without LV dysfunction, and in patients with post-ischemic (valsartan) and chronic LV systolic dysfunction (valsartan, candesartan)

  • ARBs (candesartan, irbesartan) have not demonstrated to be efficacious in patients with LV diastolic dysfunction, similarly to ACE-Is

  • ARBs (losartan, valsartan, irbesartan) have demonstrated to provide renal protection in patients with pre-clinical and clinical diabetic nephropathy

  • ARBs (candesartan) have demonstrated to induce retinopathy regression in type II diabetics (but needs confirmation)

  • Dual RAS blockade was ineffective and potentially harmful in patients without LV dysfunction and this association should be used with caution and strict surveillance of renal function

  • Dual RAS blockade (valsartan, candesartan) reduces mortality/morbidity in patients with chronic LV systolic dysfunction


  • Login