June 2009 Archives

Massie BM. I-PRESERVE. NEJM 4 Dec 2008; 359: 2456-67.

BACKGROUND: 50% of patients with heart failure have an ejection fraction > 45%. The renin-aldosterone-angiotensin system is involved in many processes associated with this syndrome - HTN, LVH, myocardial fibrosis, and vascular dysfunction. Inhibition of this system could possibly serve as a therapeutic intervention.

RESULTS

Randomization: 4564 patients screened, 4128 underwent randomization. 2067 assigned to receive Irbersartan, 2061 received placebo.

Baseline: Mean age 72y, 60% women, hypertensive heart disease 64%, HTN 88%, atrial fibrillation 29%, DM 27%, obese 41%, baseline NT-proBNP 339 pg/mL, diuretic use 83%, beta-blocker use 59%, CCB use 70%, spironolactone use 45%, ACEi use 25%

Primary Outcome: Composite end-point

All patients: 36% vs 37%, no significant differences between the two groups
All subgroups: no significant differences between the two groups

Figure 1

Secondary Outcomes: no significant differences between the two groups

Predetermined subgroup analysis: no significant differences between the two groups

Adverse Events: no significant differences between the two groups

Discussion: At the end of the study, 73% taking beta-blockers, 40% using ACEi which possibly leaves little room for more improvement. 34% discontinued drug use in both groups, consistent with other trials of this duration.

RESULTS 

Randomization: 301 enrolled, 157 to the dexamethasone group, 144 to the placebo group. Intention to treat analysis. In the dexamethasone group, 11 withdrawn, 3 lost to follow-up. In the placebo group, 11 withdrawn, 4 lost to follow-up.

Baseline: headache (94%), fever (81%), neck stiffness (94%). Positive gram stain in 215 patients (74%), positive cultures in 234 patients (78%).

Primary Outcome: Unfavorable Outcome

All patients: ARR 10%, NNT 10, p = 0.03
S. pneumo: ARR 26%, NNT 3.8, p = 0.006 
N. meningitidis: ARR 3%, NNT 33, p = 0.74
Other bacteria: ARR -11%, NNH 9, p = 0.55

Secondary Outcome: Death

All patients: 7% vs 15%, ARR 8%, NNT 12.5, p = 0.04  
S. pneumo: 14% vs 34%, ARR 20%, NNT 5, p = 0.02
N. men: 4% vs 2%, ARR -2%, NNH 50, p = 1.00

Adverse Events: no significant difference in GI bleeding, hyperglycemia, herpes zoster, or fungal infections.