Download Massie - 3320 I-PRESERVE Trial Irbesartan in

Massie - 3320
I-PRESERVE Trial
Irbesartan in heart failure with preserved EF
Co-PIs: Barry Massie and Peter Carson
Executive Committee
M. Komajda, R. McKelvie, J. McMurray, M. Zile, M. Donovan,
C. Staiger, A. Ptaszynska, C. Staiger
On Behalf of the I-PRESERVE Committees and
Investigators
Background
Massie - 3320
• Approximately 50% of heart failure patients have preserved EF (≥ 45%),
and this proportion is growing.
• In the US, HFPEF is responsible for approximately 500,000 heart failure
hospitalizations and 25,000 deaths.
• HFPEF affects primarily women and older patients, and in contrast to low
EF heart failure, hypertension is the primary underlying condition and CAD
is relatively infrequent.
• Currently no evidence-based treatment to improve patient outcomes.
• Objective
• To determine whether treatment with the angiotensin receptor blocker
irbesartan reduces mortality and morbidity in patients with HFPEF.
• Primary endpoint: All cause mortality and protocol-specified CV
hospitalizations (for heart failure, MI, stroke, arrhythmia).
• Secondary endpoints:
–
–
–
–
HF death or hospitalization
QOL (Minnesota)
Death, MI or stroke
CV death
Massie - 3320
I-PRESERVE Entry Criteria
Age 60 years
Current HF symptoms
LVEF 0.45
NYHA class II - IV
 CHF hosp. 6 months
NYHA Class III/IV
 CXR congestion
 ECG (LVH, LBBB)
 Echo (LVH, LAE)
Exclusions: Prior EF <40%; ACS or stroke ≤ 3m, hypertrophic or
restrictive CM, pericardial or valvular disease, cor pulmonale, SBP
>160 or <100, Scr >2.5, Hb <11, other conditions limiting life
expectancy, characteristics that might interfere with study protocol.
Massie - 3320
I-PRESERVE Study Design
Irbesartan
75 mg* 150 mg 300 mg
N=4,128
Enrollment
Single-blind
2 weeks
Only 1/3 pts could
enter on an ACEI
R
Forced titration
W2
W4
Maintenance
W8
M6
M 10
M 14–end
Q4 months
Placebo
Randomized, double-blind, placebo controlled trial
Follow-up continued until 1,440 primary endpoints occurred
Massie - 3320
I-Preserve Patient Characteristics
I-Preserve
(n=4,128)
Cohort & Epi Studies
72
75
Women
60%
65-70%
EF
59%
60%
HTN (1° cause)
88%(63%)
80-90% (60%)
Prior MI
23%(25%)
<20% (25%)
CABG/PCI
13%
<20%
Stroke/TIA
10%
na
Atrial fib
29%
20-30%
Diabetes
27%
20-30%
ACE I on entry
25%
Beta-blocker
60%
Spironolactone
18%
Age (mean)
I-PRESERVE: Primary Endpoint Massie - 3320
Death or hospitalization for heart failure, MI,
stroke, or arrhythmia
I-Preserve: Major Secondary
Endpoints
Cardiovascular
mortality
HR 1.02(0.87-1.19)
P=0.85
Massie - 3320
Heart failure death or
hospitalization
HR 1.01 (0.88-1.16)
P=0.89
Irbesartan
n=306
Placebo
N= 296
Placebo
n=445
Irbesartan
n=436
Massie - 3320
I-PRESERVE: Conclusions
• Largest trial conducted in patients with HFPEF, and
successfully enrolled patients similar to those in the
community.
• Irbesartan was unsuccessful in achieving its primary or
secondary outcomes.
• Irbesartan was generally safe and well tolerated.
• Our results are consistent the 2 previous trials in patients
with HFPEF that did not demonstrate a positive effect.
• For this large group of patients there is no specific
evidence-based therapy.
• In order for this field to move forward, a better
understanding of the mechanisms underlying this
syndrome and the potential targets for treatment is
required.