Value of Endothelin Receptor Inhibition with Value of Endothelin Receptor Inhibition with Tezosentan in Acute Heart Failure StudiesTezosentan in Acute Heart Failure Studies

Value of Endothelin Receptor Inhibition with Value of Endothelin Receptor Inhibition with Tezosentan in Acute Heart Failure StudiesTezosentan in Acute Heart Failure Studies

VERITAS TrialVERITAS TrialVERITAS TrialVERITAS Trial

Presented atPresented atThe American College of Cardiology The American College of Cardiology

Scientific Sessions 2004Scientific Sessions 2004

Presented by Dr. John J. V. McMurrayPresented by Dr. John J. V. McMurray

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IV Tezosentan 5 mg/hr for 30 minutes followed by 1

mg/hr for 24-72hours

n=727

IV Tezosentan 5 mg/hr for 30 minutes followed by 1

mg/hr for 24-72hours

n=727

Primary Endpoint (VERITAS 1 & 2): Change in dyspnea from baseline over the first 24 hours, as assessed by area under the curve

Primary Endpoint (pooled trials): Death or worsening heart failure at 7 days

Primary Endpoint (VERITAS 1 & 2): Change in dyspnea from baseline over the first 24 hours, as assessed by area under the curve

Primary Endpoint (pooled trials): Death or worsening heart failure at 7 days

VERITAS TrialVERITAS TrialVERITAS TrialVERITAS Trial

Presented at ACC 2005Presented at ACC 2005

Placebo5mg/hr for 30 minutes followed by 1

mg/hr for 24-72 hours

n=708

Placebo5mg/hr for 30 minutes followed by 1

mg/hr for 24-72 hours

n=708

1,449 patients with acute heart failure requiring IV therapy And received at least 1 dose of an IV diuretic, age>18 years, dyspnea at rest, enrollment within

24 hours of hospital admission40% female, mean age 70 years

68% patients had EF=29% and ischemic heart disease, 99% used IV loop diuretics, 62% used ACE Inhibitor or angiotensin receptor blockers, 47% used beta-blockers

1,449 patients with acute heart failure requiring IV therapy And received at least 1 dose of an IV diuretic, age>18 years, dyspnea at rest, enrollment within

24 hours of hospital admission40% female, mean age 70 years

68% patients had EF=29% and ischemic heart disease, 99% used IV loop diuretics, 62% used ACE Inhibitor or angiotensin receptor blockers, 47% used beta-blockers

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VERITAS Trial: Primary EndpointVERITAS Trial: Primary EndpointVERITAS Trial: Primary EndpointVERITAS Trial: Primary Endpoint

26.3%

31.9%

26.4%

33.2%

0%

5%

10%

15%

20%

25%

30%

35%

Tezosentan Placebo

26.3%

31.9%

26.4%

33.2%

0%

5%

10%

15%

20%

25%

30%

35%

Tezosentan Placebo

• There was no difference in death or worsening heart failure between the Tezosentan group compared to the placebo group at both 7 and 30 days.

• For the primary endpoint of dyspnea at 24 hours, there was no difference between the treatment groups in either of the VERITAS trials individually or together.

Primary endpoint of death or worsening heart failure at 7 and 30 days

Presented at ACC 2005Presented at ACC 2005

30 days

p=0.617 days

p=0.95

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VERITAS Trial: Adverse EventsVERITAS Trial: Adverse EventsVERITAS Trial: Adverse EventsVERITAS Trial: Adverse Events

40.4%42.4%

0%

10%

20%

30%

40%

50%

Serious Adverse Events

Tezosentan Placebo

40.4%42.4%

0%

10%

20%

30%

40%

50%

Serious Adverse Events

Tezosentan Placebo

Presented at ACC 2005Presented at ACC 2005

p=NS

There was not a significant difference in the number of serious adverse events that occurred

within the Tezosentan group compared to the placebo group.

• Hemodynamic parameters did improve with the tezosentan group group, with a 6mmHg decline in systolic blood pressure over the placebo group at 72 hours and improvements in cardiac index.

•There was no difference in survival at 6 months.

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VERITAS Trial: SummaryVERITAS Trial: SummaryVERITAS Trial: SummaryVERITAS Trial: Summary

• Among patients with acute heart failure, treatment with the endothelin receptor inhibitor tezosentan was associated with no difference in dyspnea by 24 hours or in death or worsening heart failure by 7 days compared with placebo, prompting an early termination of the trials despite no increase in adverse events.

• The lack of clinical benefit occurred despite improvements in hemodynamic parameters, including systolic blood pressure and cardiac index.

• Among patients with acute heart failure, treatment with the endothelin receptor inhibitor tezosentan was associated with no difference in dyspnea by 24 hours or in death or worsening heart failure by 7 days compared with placebo, prompting an early termination of the trials despite no increase in adverse events.

• The lack of clinical benefit occurred despite improvements in hemodynamic parameters, including systolic blood pressure and cardiac index.