IPRESERVE: Irbesartan in heart failure with PRESERVEd ejection fraction

1
I-PRESERVE Irbesartan in heart failure with
PRESERVEd ejection fraction

• Purpose
• To evaluate the effect of the angiotensin-recepto
  r blocker irbesartan on mortality and
  cardiovascular morbidity in patients with heart
  failure and a preserved left ventricular ejection
  fraction.
• Reference
• Massie BM, Carson PE, McMurray JJ, et al. for
  the I-PRESERVE Investigators. Irbesartan in
  patients with heart failure and preserved
  ejection fraction. N Engl J Med
  200835924562467.

2
I-PRESERVE Irbesartan in heart failure with
PRESERVEd ejection fraction - TRIAL DESIGN -

• Design
• Multicenter, multinational, randomized,
  double-blind, placebo-controlled trial.
• Patients
• 4128 patients who were 60 years old and who had
  symptomatic heart failure in New York Heart
  Association class II, III or IV, and a left
  ventricular ejection fraction of 45.
• Follow-up and primary endpoint
• The primary endpoint was a composite of death
  from any cause or hospitalization for a
  cardiovascular cause (heart failure, myocardial
  infarction, unstable angina, arrhythmia or
  stroke). Mean follow-up was 49.5 months.
• Treatment
• Irbesartan 300 mg daily or matching placebo.

3
I-PRESERVE Irbesartan in heart failure with
PRESERVEd ejection fraction - TRIAL DESIGN
continued -
Baseline characteristics
Irbesartan
Placebo
(n2067)
(n2061)
Mean age (years)
72
72
Female sex ()
59
61
White race ()
94
93
NYHA class
II
21
22
III
77
76
IV
3
3
137/79
136/79
Mean blood pressure (mm Hg)
Mean ejection fraction
0.59
0.60
Cause of heart failure ()
Ischemia
26
24
Hypertension
64
63
Heart failure hospitalizations within previous 6
months ()
44
44
Massie et al. N Engl J Med 200835924562467.
4
I-PRESERVE Irbesartan in heart failure with
PRESERVEd ejection fraction - RESULTS -

• The primary endpoint occurred in 742 patients
  (36) in the irbesartan group and in 763 patients
  (37) in the placebo group.
• The hazard ratio for the primary endpoint was
  0.95 for irbesartan versus placebo (p0.35).
• There were no significant differences between the
  study groups for the individual components of the
  primary endpoint or for any pre-specified
  secondary endpoint.
• The neutral effect of irbesartan treatment was
  consistent across all pre-specified subgroups.
• Irbesartan was well tolerated and was not
  associated with an excess of adverse events in
  comparison with placebo.

5
I-PRESERVE Irbesartan in heart failure with
PRESERVEd ejection fraction - RESULTS continued -
Kaplan-Meier curves for the primary
endpointdeath from any cause or hospitalization
for cardiovascular causes
No. at risk Irbesartan Placebo
2067 2061
1640 1618
1088 1051
1812 1808
1513 1466
1929 1921
1569 1539
816 776
1730 1715
1291 1246
497 446
Massie et al. N Engl J Med 200835924562467.
6
I-PRESERVE Irbesartan in heart failure with
PRESERVEd ejection fraction - RESULTS continued -
Primary and secondary endpoints

No. of patients with event
Irbesartan (n2067)
Placebo (n2061)
Hazard ratio
p value
Primary composite endpoint
742
763
0.95
0.35
Components of the primary endpoint
Death
221
226
1.00
0.98
Hospitalization for cardiovascular cause
521
537
0.95
0.44
Secondary endpoints
Death from any cause
445
436
1.00
0.98
Death or hospitalization for heart failure
428
438
0.96
0.51
Death from a cardiovascular cause
311
302
1.01
0.92
Hospitalization forworsening heart failure
325
336
0.95
0.50
Hospitalization for any cause
1152
1126
1.02
0.64
Median change in score on theMLHF scale at 6
months
8
7
0.85
Median change in NT pro-BNPat 6 months (pg/ml)
13
2
0.14
Abbreviations MLHF, Minnesota Living with Heart
Failure scaleNT pro-BNP, plasma N-terminal pro
B-type natriuretic peptide.
Massie et al. N Engl J Med 200835924562467.
7
I-PRESERVE Irbesartan in heart failure with
PRESERVEd ejection fraction - SUMMARY -

• In patients with heart failure and a preserved
  ejection fraction, treatment with the
  angiotensin-receptor blocker irbesartan did not
  improve mortality or cardiovascular morbidity in
  comparison with placebo.