VHeFT II: VasodilatorHeart Failure Trial

1
V-HeFT II VasodilatorHeart Failure Trial

• Purpose
• To compare the efficacy of the ACE inhibitor
  enalapril with that of hydralazine plus
  isosorbide dinitrate in patients with chronic
  congestive heart failure
• Reference
• Cohn JN, Johnson G, Ziesche S et al. A
  comparison of enalapril with hydralazineisosorbid
  e dinitrate in the treatment of chronic
  congestive heart failure. N Engl J Med
  199132530310.

2
V-HeFT II VasodilatorHeart Failure Trial-
TRIAL DESIGN -

• Design Multicenter, randomized, double-blind
• Patients 804 patients, aged 1875 years, with
  evidence of cardiac dysfunction in association
  with reduced exercise tolerance, receiving
  digoxin and diuretic therapy patients with MI in
  previous 3 months or angina pectoris limiting
  exercise excluded
• Follow up and primary endpoint Primary
  endpoint all-cause mortality. Mean 2.5 years
  follow up.
• Treatment Patients randomized to either
• Enalapril 10 mg twice daily, placebo matching
  hydralazine and placebo matching isosorbide
  dinitrate, or
• Hydralazine 75 mg and isosorbide dinitrate 40 mg,
  both four times daily, and placebo matching
  enalapril

3
V-HeFT II VasodilatorHeart Failure Trial-
RESULTS -

• Mortality in enalapril arm, compared with
  hydralazineisosorbide
• significantly lower at 2 years (18 vs. 25,
  P0.016)
• lower over entire trial period (0.55.7 years),
  but not significantly so (32.8 vs. 38.2, P0.08)
• differences attributed to significantly fewer
  sudden deaths
• Left ventricular ejection fraction significantly
  higher in both arms over 3 years (P0.0001), and
  significantly more so with hydralazineisosorbide
  than with enalapril at 13 weeks (P0.026)
• O2 consumption at peak exercise levels
  significantly increased above baseline by
  hydralazineisosorbide at 13 weeks and 6 months
  (by 0.6 and 0.8 mL/kg/min, respectively, both
  Plt0.0001) but not by enalapril, declining after 1
  year
• Incidence of hypotension and cough significantly
  higher with enalapril headache significantly
  higher with hydralazineisosorbide

4
V-HeFT II VasodilatorHeart Failure Trial-
RESULTS continued-
Cumulative mortality
Cumulative
0.75
mortality
0.50
0.25

0
0
12
24
36
48
60
Months after randomization
Cohn et al. N Engl J Med 1991 32530310.

5
V-HeFT II VasodilatorHeart Failure Trial-
RESULTS continued-
Cause of death
Hydralazine

isosorbide
Enalapril (n403)
dinitrate (n401)
P
Deaths
Cumulative
Deaths
Cumulative
No. ()
mortality,
No. ()
mortality,
All
0.08




153
132









Other
7
11



Percentage of cardiac deaths
Cohn et al. N Engl J Med 1991 32530310.
6
V-HeFT II VasodilatorHeart Failure Trial-
RESULTS continued-
Mean change in left ventricular ejection fraction
Change in
0.05
ejection fraction
0.04
0.03
0.02
Enalapril
0.01
Hydralazine


isosorbide
0
dinitrate
13 weeks
1 year
2 years
Time after randomization
Cohn et al. N Engl J Med 1991 32530310.
7
V-HeFT II VasodilatorHeart Failure Trial-
SUMMARY -

• In patients with chronic congestive heart
  failure
• Enalapril conferred greater reduction in
  mortality than hydralazineisosorbide for at
  least 2 years, due to lower incidence of sudden
  death
• Treatment with either enalapril or
  hydralazineisosorbide increased left ventricular
  ejection fraction
• Hydralazineisosorbide increased O2 consumption
  at peak exercise levels for the first year