The Studies of Oral Enoximone Therapy in The Studies of Oral Enoximone Therapy in Advanced Heart FailureAdvanced Heart Failure

The Studies of Oral Enoximone Therapy in The Studies of Oral Enoximone Therapy in Advanced Heart FailureAdvanced Heart Failure

ESSENTIALESSENTIALESSENTIALESSENTIAL

Presented atPresented atThe European Society of Cardiology Congress The European Society of Cardiology Congress

20052005

Presented by Dr. Marco MetraPresented by Dr. Marco Metra

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Oral Enoximone 25 mg three times daily, up-titrated to 50 mg

three times daily; n=926

Oral Enoximone 25 mg three times daily, up-titrated to 50 mg

three times daily; n=926

Primary Endpoints: 1) Reduction in time to all-cause mortality or cardiovascular (CV) hospitalization in the pooled components; 2) increase in the six minute walk test distance in each component individually; 3) symptomatic improvement on the Patient Global Assessment (PGA) questionnaire in each component individually

Primary Endpoints: 1) Reduction in time to all-cause mortality or cardiovascular (CV) hospitalization in the pooled components; 2) increase in the six minute walk test distance in each component individually; 3) symptomatic improvement on the Patient Global Assessment (PGA) questionnaire in each component individually

ESSENTIALESSENTIALESSENTIALESSENTIAL

Presented at ACC 2005Presented at ACC 2005

Placebo N=928

Placebo N=928

1854 patients who met the following criteria: Age ≥18 years, ischemic or non-ischemic cardiomyopathy, NYHA Class III or IV, one hospitalization or two outpatient visits for treatment of worsening heart failure in prior 12 months requiring the administration of intravenous heart failure therapy, impaired cardiac function (LVEF ≤30%), concomitant treatment with optimal conventional heart failure therapy (beta-blockers and ACE inhibitors or angiotensin receptor

blockers).

1854 patients who met the following criteria: Age ≥18 years, ischemic or non-ischemic cardiomyopathy, NYHA Class III or IV, one hospitalization or two outpatient visits for treatment of worsening heart failure in prior 12 months requiring the administration of intravenous heart failure therapy, impaired cardiac function (LVEF ≤30%), concomitant treatment with optimal conventional heart failure therapy (beta-blockers and ACE inhibitors or angiotensin receptor

blockers).

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ESSENTIAL: Primary EndpointESSENTIAL: Primary EndpointESSENTIAL: Primary EndpointESSENTIAL: Primary Endpoint

458465

400

410

420

430

440

450

460

470

480

490

500

Enoximone Placebo

458465

400

410

420

430

440

450

460

470

480

490

500

Enoximone Placebo

• The primary endpoint of cardiovascular hospitalization or all-cause mortality did not differ significantly between groups

Cardiovascular Hospitalization/All-cause Mortality

P=0.71

Presented at ACC 2005Presented at ACC 2005

www. Clinical trial results.org

ESSENTIAL: Primary EndpointESSENTIAL: Primary EndpointESSENTIAL: Primary EndpointESSENTIAL: Primary Endpoint

10

00

2

4

6

8

10

12

14

16

18

20

Enoximone Placebo

10

00

2

4

6

8

10

12

14

16

18

20

Enoximone Placebo

•Median change in six minute walk distance was significantly different for the enoximone group compared to the placebo group within the North/South America cohort, but did not differ significantly between groups in the European cohort

Median Change in six-minute walk distance (m) from baseline to six months

East/West EuropeP=0.82

North/South AmericaP=0.025

16.515

0

2

4

6

8

10

12

14

16

18

20

Enoximone Placebo

16.515

0

2

4

6

8

10

12

14

16

18

20

Enoximone Placebo

www. Clinical trial results.org

ESSENTIAL: Primary EndpointESSENTIAL: Primary EndpointESSENTIAL: Primary EndpointESSENTIAL: Primary Endpoint

43%46%

0%

10%

20%

30%

40%

50%

Enoximone Placebo

43%46%

0%

10%

20%

30%

40%

50%

Enoximone Placebo

Marked improvement Reported on the Patient Global Assessment (PGA) Questionnaire

29%31%

0%

10%

20%

30%

40%

50%

Enoximone Placebo

29%31%

0%

10%

20%

30%

40%

50%

Enoximone Placebo

North/South America

p=0.79

East/West Europe

P=0.11•There was no significant difference in reported symptomatic improvement in patients treated with enoximone compared with placebo in either the American or European cohorts

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ESSENTIAL Trial SummaryESSENTIAL Trial SummaryESSENTIAL Trial SummaryESSENTIAL Trial Summary

• Among patients with advanced chronic heart failure who were already receiving optimal conventional therapy, treatment with enoximone was not associated with improvements in all-cause mortality or CV hospitalization

• For distance walked in a six-minute walk test, the median change from baseline to 6 months was 10 meters (p=0.025) with enoximone vs. placebo in the North/South America cohort. In the European cohort, the difference was only 1.5 meters with enoximone vs. placebo (p=0.82)

• There was no difference in symptomatic improvement between groups as reported on the Patient Global Assessment Questionnaire.

• Among patients with advanced chronic heart failure who were already receiving optimal conventional therapy, treatment with enoximone was not associated with improvements in all-cause mortality or CV hospitalization

• For distance walked in a six-minute walk test, the median change from baseline to 6 months was 10 meters (p=0.025) with enoximone vs. placebo in the North/South America cohort. In the European cohort, the difference was only 1.5 meters with enoximone vs. placebo (p=0.82)

• There was no difference in symptomatic improvement between groups as reported on the Patient Global Assessment Questionnaire.