MERIT-HF: Metoprolol CR/XL Randomized Intervention Trial in congestive Heart Failure
Purpose
To determine whether metoprolol controlled/extended release
(CR/XL) once daily, in addition to standard therapy, can lower mortality in patients with decreased ejection fraction and
symptoms of heart failure
Reference
MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic
heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001–7.
MERIT-HF: Metoprolol CR/XL Randomized Intervention Trial in congestive Heart Failure - TRIAL DESIGN -
Design
Randomized, double-blind, placebo-controlled
Patients
3991 patients with left ventricular ejection fraction <0.40 and NYHA class II-IV heart failure, stabilized by optimum standard therapy (any combination of diuretics + ACE inhibitor)
Follow up and primary endpoint
Aim 2.4 years follow up. Primary endpoint all-cause mortality
Treatment
Patients assigned metoprolol received 12.5 (NYHA III-IV) or 25 mg (NYHA II) once daily, increasing over 8 weeks to maximum target dose 200 mg once daily
MERIT-HF: Metoprolol CR/XL Randomized Intervention Trial in congestive Heart Failure - RESULTS -
Study halted at mean follow up of 1 year on recommendation of independent safety committee because predefined criteria met and exceeded:
All-cause mortality significantly lower in metoprolol CR/XL group (145 vs. 217, 34% risk reduction, P=0.0062)
Significantly fewer cardiovascular deaths (128 vs. 203), sudden deaths (79 vs. 132) and death from worsening heart failure (30 vs. 58)
Drug well tolerated, as defined by permanent early discontinuation of treatment (13.9% of metoprolol CR/XL group versus 15.3% placebo)
MERIT-HF: Metoprolol CR/XL Randomized Intervention Trial in congestive Heart Failure - RESULTS continued -
MERIT-HF Study Group.
Lancet
1999;
353
:2001
–
7.
No patients lost to follow up
MERIT-HF trial profile
3991 patients
randomized
2001 patients
placebo
217 patient
deaths
1784 patients alive
1539 patients on treatment
145 patient
deaths
1990 patients
metoprolol CR/XL
1845 patients alive
1614 patients on treatment
MERIT-HF: Metoprolol CR/XL Randomized Intervention Trial in congestive Heart Failure - RESULTS continued -
Cumulative all-cause mortality
MERIT-HF Study Group.
Lancet
1999;
353
:2001
–
7.
Follow up (months)
P = 0.0062 (adjusted for
interim analysis)
P = 0.00009 (nominal)
0
0
3
6
9
12
16
18
21
5
10
15
20
Placebo
Metoprolol CR/XL
Cumulative mortality
(%)
MERIT-HF: Metoprolol CR/XL Randomized Intervention Trial in congestive Heart Failure - RESULTS continued -
MERIT-HF Study Group.
Lancet
1999;
353
:2001
–
7.
0
0.5
1.0
1.5
Relative risk for mortality
Relative risk (95% CI)
Mortality
Metoprolol CR/XL better
Risk
reduction
(%)
Total mortality
Cardiovascular mortality
Sudden death
Death from worsening
heart failure
34
38
41
49
0.0062
0.00003
0.0002
0.0023
P
MERIT-HF: Metoprolol CR/XL Randomized Intervention Trial in congestive Heart Failure - SUMMARY -
Metoprololol CR/XL once daily in addition to optimum standard therapy:
Was well tolerated and did not increase risk in any of subgroups analyzed
Improved survival in clinically stable patients, equating to prevention of 1 death per 27 patients treated per year