MERIT-HF Press-Release 11 November, 1998
The beta-blocker metoprolol CR/XL significantly
improves survival in patients with heart failure
MERIT-HF Study shows about 35% reduction in mortality
Adding the beta-blocker metoprolol CR/XL to standard
treatment in patients with congestive heart failure can help to improve survival
and reduce all-cause mortality by about 35 per cent. This preliminary result of
the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF),
the largest heart failure trial ever completed using a beta-blocker, was
presented today at the 71st Scientific Sessions of the American Heart
Association.1-2 The clinically important and highly positive outcome led
the Independent Safety Committee to recommend the early closure of the study;
this took place on 31 October, 1998.
The discovery that beta-blockade could improve cardiac
function in patients with heart failure was done at Sahlgrenska University
Hospital, Göteborg University, Gothenburg, Sweden, in the early 70's.3
Further studies initiated by the Gothenburg Group also indicated that long-term
treatment with the beta-blocker metoprolol could have the potential to improve
prognosis, prolong life and prevent heart transplantation in this deadly
disease.4-6 These findings made the base for the large-scale
international MERIT-HF Study.
Professor Sidney Goldstein, Henry Ford Hospital, Heart
and Vascular Institute, Detroit, Michigan, USA, and Co-Chairman of the MERIT-HF
Executive Committee, who presented the results commented: "The highly
significant decrease in mortality of about 35 per cent associated with
metoprolol CR/XL has important implications for doctors and patients. The
statement made by the Independent Safety Committee that mortality results were
consistent across predefined subgroups is reassuring, as is the statement that
the reduction in the combination of deaths and hospitalisations is consistent
with the mortality results."
"By adding beta-blocker therapy with metoprolol
CR/XL to other standard therapy such as diuretics and ACE-inhibitors many lives
can be saved" said Dr Stephen Gottlieb, the US National Co-ordinator of the
MERIT-HF Study.
Chronic or congestive heart failure is a disease in
which the heart fails to propel the blood normally. As a result the functions of
many organs in the body are disturbed and symptoms such as fatigue and
breathlessness develop. The most frequent underlying causes to chronic heart
failure are previous myocardial infarction and high blood pressure. The disease
is very disabling and the risk to die is considerably increased. Heart failure
is an important and increasing public health problem both in Europe and in the
USA. In the USA it is estimated that there are four to five million people with
heart failure, with 400,000 cases occurring each year.7 Chronic heart
failure results in almost one million hospitalisations each year and is the most
common discharge diagnosis in patients over 65 in both Europe and in the USA. 7-11
3,991 patients in 14 countries (Belgium, Czech
Republic, Denmark, Finland, Germany, Hungary, Iceland, The Netherlands, Norway,
Poland, Sweden, Switzerland, UK, USA) took part in the MERIT-HF Study. The main
aim of the study was to investigate the impact of metoprolol CR/XL compared with
placebo on survival in patients with heart failure. Other important outcome
measures include sudden death and hospitalisation for heart failure, and also
quality of life.2 Full analysis of the MERIT-HF data is now underway.
Professor Åke Hjalmarson, Division of Cardiology,
Sahlgrenska University Hospital, Göteborg University, Gothenburg, Sweden,
and Co-Chairman of the MERIT-HF Study Executive Committee, is the leader of the
group which first proposed and investigated the use of beta-blockers in heart
failure.3-6 He said: "Despite extensive research supporting the
use of beta-blockers in reducing heart attacks and sudden deaths in
post-myocardial infarction, they continue to be underappreciated and
underused.12 The MERIT-HF Study results firmly establish the important
role of the lipophilic beta-blocker metoprolol CR/XL in heart failure, one of
the most common, debilitating and costly cardiovascular conditions. This finding
should lead to a re-appraisal of beta-blockers in cardiovascular medicine
including patients with hypertension as well as patients in the post-MI
situation.12-16
The Independent Safety Committee for MERIT-HF chaired
by Professor Desmond Julian from London, stated in its report that
discontinuation of study medication was similar in the metoprolol CR/XL and
placebo groups. "This shows that the treatment was very well
tolerated", commented Professor Åke Hjalmarson. "We chose to use
metoprolol CR/XL in the MERIT-HF Study because of its favourable tolerability
profile and easy once a day usage.17,18 When treating patients with heart
failure in the past we used the old 50 mg metoprolol tablet 3 times daily. Now
we can give up to one 200 mg metoprolol CR/XL tablet once daily in the morning,
this gives a smooth, sustained effect over 24 hours."17,18 " With
this new high-tech medicine we also hope to reduce side-effects and improve
quality of life, issues that will now be analyzed",19 said Professor
Hjalmarson.
The scientific responsibility for the MERIT-HF study
lies with the International Executive Committee and the International Steering
Committee, the latter including National Co-ordinators from the 14 participating
countries (see separate list enclosed).2
So far information on outcome data is based on the
statement from the Independent Safety Committee. A thorough analysis of all data
from the MERIT-HF Study will now be made by the members of the International
Steering Committee. Results from these analyses will be presented at the ACC
meeting in March, 1999.
Astra AB of Sweden is the sponsor of the MERIT-HF Study
and the inventor and manufacturer of the lipophilic, cardioselective
beta-blocker metoprolol CR/XL. The company plans to file a licence application
for metoprolol CR/XL in heart failure in the second quarter of 1999. Metoprolol
CR/XL is sold under the following trade names: Beloc-Zok® (Germany,
Switzerland), Betaloc ZOK® (Hungary, Poland), Selokeen ZOK® (The Netherlands), Seloken ZOC® (Finland,
Iceland, Sweden), Selozok®
(Belgium), Selo-ZOK® (Denmark, Norway),
Toprol XL® (USA).
References
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Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF): An update
after complete randomization. The International Steering Committee on behalf of
the MERIT-HF Study Group". Paper presented at the 71st Scientific Sessions
of the American Heart Association, Dallas, Texas, 10 November, 1998.
2. The International Steering
Committee on behalf of the MERIT-HF Study Group. Rationale, Design, and
Organization of the Metoprolol CR/XL Randomized Intervention Trial in Heart
failure (MERIT-HF). Am J Cardiol 1997;80 Suppl 9B:54J-8J.
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