"Physicians prescribing metoprolol
instead of carvedilol to save money may be being 'penny-wise
and pound-foolish'", concludes Thomas Delea, one of the
authors of a study on the relevance of the Carvedilol
Or Metoprolol European Trial (COMET) to patient care in
the real world. Mr Delea is a Senior Consultant with Policy
Analysis Inc. in Brookline, MA, and his retrospective
study published in the March 10 issue of the International
Journal of Cardiology compares the risks of mortality
and hospitalization, and the costs of inpatient care for
chronic heart failure (CHF) patients receiving either
metoprolol or carvedilol.
Mr Delea's statement contradicts
earlier studies, such as a Canadian one published in
the September 2001 issue of the American Heart Journal,
which concluded that both metoprolol and carvedilol
prolong life for a relatively low cost. However, according
to the latest study, carvedilol is superior in terms
of benefits as well as cost of care.
COMET'S
RESULTS CONFIRMED
The first set of COMET results, published July 5, 2003
in The Lancet, showed that carvedilol reduced
the relative risk of cardiac mortality by 17% compared
to metoprolol.
However, critics of this earlier
trial suggested that the doses used in the study didn't
produce equivalent beta-blockades because a high dose
of carvedilol (25mg twice daily) was compared with a
low dose of metoprolol (50mg twice daily). This made
it difficult to confirm the claims of the study.
The results of Mr Delea's study
looked to counter those criticisms. "In our study, in
which there were no such constraints on dosing, outcomes
were better with carvedilol," notes Mr Delea. Using
a claims database from a US health benefits company,
the researchers selected 887 carvedilol
and an equal number of metoprolol patients meeting the
inclusion criteria: a prescription for carvedilol or
metoprolol between September 1997 and August 2000; prior
diagnosis of heart failure; prior prescriptions for
a loop diuretic and an ACE inhibitor; and no prior prescriptions
for a beta-blocker. Mean followup duration was 11 months.
The team's findings were consistent
with those of COMET. They showed a 22% reduction in
relative risk of all cause mortality for carvedilol.
Moreover, the expected costs of inpatient care at 36
months were lower and offset the additional cost of
carvedilol for the same period.
The mean doses prescribed were
70mg for metoprolol and 24mg for carvedilol daily. Adjusting
for non-compliance, actual doses for both drugs were
suboptimal at 44mg/day and 14mg/day, respectively.
The authors note that the two
drugs "have been shown to produce nearly equivalent
effects on exercise heart rates (and by implication,
beta blockade) when given in a dosage ratio of less
than 2:1, our results provide additional evidence that
the benefits of carvedilol may extend beyond [beta]
blockade alone." However, Mr Delea cautions, "Our results
may not be generalizable to comparisons of carvedilol
versus metoprolol succinate (extended release)."
Additional COMET results were published
online on March 23 in the European Journal of Heart
Failure. "Switching beta-blockers is a practical,
safe and well-tolerated strategy to optimize treatment
of CHF," note the authors. They also say that patients
who switched to carvedilol showed the lowest rate of
adverse events.
Int J Cardiol Mar10, 2005;99(1):117-24
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