MERITHF: Metoprolol CRXL Randomized Intervention Trial in congestive Heart Failure

1
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 199935320017.

2
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 lt0.40 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

3
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, P0.0062)
• 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)

4
MERIT-HF Metoprolol CR/XL Randomized
Intervention Trial in congestive Heart Failure-
RESULTS continued -

MERIT-HF trial profile
3991 patients
randomized
1990 patients
2001 patients
placebo
metoprolol CR/XL
217 patient
145 patient
deaths
deaths
1784 patients alive
1845 patients alive
1614 patients on treatment
1539 patients on treatment
No patients lost to follow up
MERIT-HF Study Group.
Lancet
1999
353
2001

7.
5
MERIT-HF Metoprolol CR/XL Randomized
Intervention Trial in congestive Heart Failure-
RESULTS continued -

Cumulative all-cause mortality
20
Cumulative mortality ()
Placebo
Metoprolol CR/XL
15
10
5
P 0.0062 (adjusted for
interim analysis)
P 0.00009 (nominal)
0
0
3
6
9
12
16
18
21
Follow up (months)
MERIT-HF Study Group.
Lancet
1999
353
2001

7.
6
MERIT-HF Metoprolol CR/XL Randomized
Intervention Trial in congestive Heart Failure -
RESULTS continued -

Relative risk for mortality
Risk
Mortality
Metoprolol CR/XL better
P
reduction
()
Total mortality
34
0.0062
Cardiovascular mortality
38
0.00003
Sudden death
41
0.0002
Death from worsening
49
0.0023
heart failure
0
0.5
1.0
1.5
Relative risk (95 CI)
MERIT-HF Study Group.
Lancet
1999
353
2001

7.
7
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