impact of isdn-hydralazine on mortality and morbidity of african-american patients with heart...

Impact of ISDN-hydralazine on mortality and Impact of ISDN-hydralazine on mortality and morbidity of African-American patients with Heart morbidity of African-American patients with Heart

FailureFailure

Impact of ISDN-hydralazine on mortality and Impact of ISDN-hydralazine on mortality and morbidity of African-American patients with Heart morbidity of African-American patients with Heart

FailureFailure

A-Heft TrialA-Heft TrialA-Heft TrialA-Heft Trial

Presented atPresented atAmerican Heart AssociationAmerican Heart Association

Scientific Sessions 2004Scientific Sessions 2004

Presented by Dr. A.L. TaylorPresented by Dr. A.L. Taylor

www. Clinical trial results.org

Isosorbide dinitrate (ISDN) plus hydralazine

Tablet containing 20 mg ISDN and 37.5 mg hydralazine (BiDil®, NitroMed) 3X daily. Dosage could be doubled by

enrolling physician. n=518

44.2% female44.8% diabetic

Isosorbide dinitrate (ISDN) plus hydralazine

Tablet containing 20 mg ISDN and 37.5 mg hydralazine (BiDil®, NitroMed) 3X daily. Dosage could be doubled by

enrolling physician. n=518


Primary Endpoint: Weighted composite of all-cause death, first hospitalization for heart

failure, and change in quality of life at a mean follow-up of 10 months

Primary Endpoint: Weighted composite of all-cause death, first hospitalization for heart

failure, and change in quality of life at a mean follow-up of 10 months

A-Heft TrialA-Heft TrialA-Heft TrialA-Heft Trial

Presented at AHA 2004Presented at AHA 2004

Placebo n=532


Placebo n=532


1,050 African-American patients with advanced heart failureNew York Heart Association (NYHA) class 3-4 for > 3 months

LV function < 35% (< 40% if LV dilated per echo)90% receiving diuretics, 69% ACE-inhibitor, 17% angiotensin receptor blocker, 74% beta-blocker

1,050 African-American patients with advanced heart failureNew York Heart Association (NYHA) class 3-4 for > 3 months

LV function < 35% (< 40% if LV dilated per echo)90% receiving diuretics, 69% ACE-inhibitor, 17% angiotensin receptor blocker, 74% beta-blocker


A-Heft Trial: Primary Endpoint A-Heft Trial: Primary Endpoint A-Heft Trial: Primary Endpoint A-Heft Trial: Primary Endpoint

-0.1

-0.5-1

0

0

0

0

0 ISDN-hydralazine Placebo

-0.1

-0.5-1

0

0

0

0

0 ISDN-hydralazine Placebo


Primary Composite Scorep = 0.01

• The primary weighted composite of all-cause mortality, first hospitalization for HF and change in quality-of-life was significantly lower in the ISDN-hydralazine group than in the placebo group at a mean follow-up of 10 months


A-Heft Trial: Primary Endpoint A-Heft Trial: Primary Endpoint A-Heft Trial: Primary Endpoint A-Heft Trial: Primary Endpoint

All-Cause Mortalityp=0.02

6.2

10.2

0

3

6

9

12

%

ISDN-Hydralazine Placebo

All-Cause Mortalityp=0.02

6.2

10.2

0

3

6

9

12

%


First HF Hospitalizationp=0.001

16.4

24.4

0

5

10

15

20

25%

ISDN-Hydralazine Selective Invasive

First HF Hospitalizationp=0.001

16.4

24.4

0

5

10

15

20

25%

ISDN-Hydralazine Selective Invasive


Change in quality-of-life score at 6 months

p=0.02

-5.5

-2.7

-6

-5

-4

-3

-2

-1

0

%


Change in quality-of-life score at 6 months

p=0.02

-5.5

-2.7

-6

-5

-4

-3

-2

-1

0

%


All individual components of the primary composite endpoint were significantly improved with ISDN-hydralazine therapy, namely death, first hospitalization for

heart failure, and change in the quality-of-life score (a larger negative score indicates a better quality of life).


A-Heft Trial: Mortality A-Heft Trial: Mortality A-Heft Trial: Mortality A-Heft Trial: Mortality

6.2

10.2

0

4

8

12

%

ISDN-hydralazine Placebo

6.2

10.2

0

4

8

12

%



Mortality

p = 0.01 • A significant reduction in mortality in the ISDN-hydralazine group began to emerge at 6 months and continued to diverge through follow-up, prompting an early end to the trial


A-Heft Trial: Adverse effects A-Heft Trial: Adverse effects A-Heft Trial: Adverse effects A-Heft Trial: Adverse effects

47.5

29.3

19.2

12.3

05

101520253035404550

headache dizziness

%


47.5

29.3

19.2

12.3

05

101520253035404550

headache dizziness

%


8.7

3.1

12.8

7.0

0

5

10

15

all exacerbation ofCHF

severe exacerbationof CHF

%


8.7

3.1

12.8

7.0

0

5

10

15

all exacerbation ofCHF

severe exacerbationof CHF

%



Adverse events of headache and dizziness were significantly higher in the ISDN-hydralazine group, while the more serious adverse events of exacerbation of CHF were significantly lower in the ISDN-hydralazine group than in the placebo group

p=<0.001

p=<0.001

p=0.04

p=0.005


A-Heft Trial: Summary A-Heft Trial: Summary A-Heft Trial: Summary A-Heft Trial: Summary

• Among African-American patients with advanced heart failure, the primary weighted composite of all-cause death, first hospitalization for heart failure, and change in quality of life was significantly lower in the ISDN-hydralazine group than in the placebo group at a mean follow-up of 10 months

• All individual components of the primary endpoint were significantly improved with ISDN-hydralazine therapy compared to placebo

• The trial was stopped after 1,050 of the planned 1,100 patients had been enrolled due to the significantly lower incidence of mortality in the ISDN-hydralazine group

• This was the first study of this therapy to be conducted solely in African-American patients, a population disproportionately affected by heart failure

• Future studies are warranted for the identification of genetic markers more specific to drug efficacy to replace the broader category of race as a treatment criteria

• Among African-American patients with advanced heart failure, the primary weighted composite of all-cause death, first hospitalization for heart failure, and change in quality of life was significantly lower in the ISDN-hydralazine group than in the placebo group at a mean follow-up of 10 months

• All individual components of the primary endpoint were significantly improved with ISDN-hydralazine therapy compared to placebo

• The trial was stopped after 1,050 of the planned 1,100 patients had been enrolled due to the significantly lower incidence of mortality in the ISDN-hydralazine group

• This was the first study of this therapy to be conducted solely in African-American patients, a population disproportionately affected by heart failure

• Future studies are warranted for the identification of genetic markers more specific to drug efficacy to replace the broader category of race as a treatment criteria

impact of isdn-hydralazine on mortality and morbidity of african-american patients with heart...

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