CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 2, March 2012
e12
AFRICA
also placed urgently on the heart transplant list.
Following these arrhythmic events, the patient mentioned
(after repeated questioning) that she had been taking a capsule
for weight reduction which she had not considered as prescrip-
tion medication. The capsule was made up by the pharmacist
on prescription from a doctor at a weight-loss clinic. She had
been on these capsules for more than two years. A copy of the
prescription was obtained. This included liothyronine, metform-
in, hydrochlorothiazide diuretic, sibutramine and fucus (also
known as bladderwrack).
Although the patient remained critically ill for the next 48
hours, she did not require intubation or insertion of the LVAD,
and had no further arrhythmias. She gradually improved and was
weaned off the inotropes and diuretics. Twelve days after admis-
sion an echocardiogram was repeated and showed the ejection
fraction to have risen to 45%, and the valvular regurgitation
to have diminished substantially. The pro-BNP level was now
down to 958 pg/ml. The patient was submitted for programmed
electrical stimulation to see if an arrhythmia was inducible, but
this study was negative. However she was documented to have a
prolonged QTc interval of 0.55 seconds.
She was subsequently discharged home on oral ACE inhibi-
tors, beta-blockers and amiodarone. She was strongly advised
not to take any other medications or supplements. It is planned
to stop the amiodarone after a further two months and then repeat
the stimulation study. The continued need for ACE inhibitors and
beta-blockers will be re-evaluated at follow up.
Discussion
This patient presented with a severe cardiomyopathy in gross
heart failure with malignant arrhythmias. All potential contribut-
ing causes were excluded and it was concluded that the entire
clinical picture could be explained by the adverse effects of
the weight-loss concoction of medication. This case illustrates
the dangers of combination therapy for weight reduction. The
patient was fortunate in that the severe myocardial depression
was reversible, and that she was in an appropriate facility when
she manifested with the malignant ventricular arrhythmias.
The myocardial depression noted could have had a similar
pathogenesis to that of tachycardia-induced cardiomyopathy.
Sibutramine inhibits norepinephrine and serotonin re-uptake,
resulting in an increased energy expenditure.
1
Due to its sympa-
thomimetic effect, it is associated with an increase in blood
pressure and pulse rate.
2
There is a published report of its asso-
ciation with a reversible cardiomyopathy.
3
The patient also had
very rapid atrial fibrillation. This could have been related to the
sibutramine itself, but the exogenous thyroid supplements were
a major aggravating factor.
Sibutramine has also been reported to be associated with
serious arrhythmias.
4,5
In this patient the use of diuretics (and
potential potassium loss) could also have enhanced the poten-
tial for serious arrhythmia, particularly with the documented
QTc prolongation. There was no history of sudden death in the
family nor of syncope, but obviously the substrate for malignant
arrhythmias was present and activated by the concoction of
medication taken.
There is a report of prolonged QT interval associated with
sibutramine that caused resuscitated ventricular fibrillation in
an otherwise health 51-year-old woman.
6
In that case, the QT
interval returned to normal by day two after cessation of the drug
after four months of therapy.
It remains to be seen whether the QT interval will return to
normal in the current case, where the usage of the drug was for
more than two years. Fucus (bladderwrack) can cause thyroid
disorders as it contains high amounts of iodine, and may have
contributed to the suppressed TSH and rapid tachycardias that the
patient had on admission. The Natural Medicines Comprehensive
Database lists fucus as ‘possible unsafe’ when consumed orally.
7
It is also important to note that the package insert for sibutramine
lists hyperthyroidism as a contraindication to its use.
8
Despite
this, the patient was prescribed liothyronine. All of these factors
may have contributed to the markedly suppressed TSH level,
which reflects sub-clinical hyperthyroidism.
The SCOUT study, comparing sibutramine to placebo,
showed more cases of resuscitated cardiac arrest with the active
agent, but this did not reach statistical significance.
9
Sibutramine
was withdrawn from the European market in 2010 and has now
been withdrawn worldwide, primarily due to an increase in non-
fatal myocardial infarction and non-fatal stroke in patients with
pre-existing cardiovascular disease.
10,11
Conclusion
The lessons illustrated in this case highlight that when patients
are considered for pharmacological treatment for weight reduc-
tion, there needs to be a thorough evaluation of the patient and
open discussion about the risks thereof. Close monitoring of
such patients is essential. While the use of sibutramine was
probably directly implicated in the pathogenesis of this case, the
other drugs used in the dispensed capsule were at least actively
contributory. Individually, the agents may certainly be associ-
ated with adverse effects, but their combination is potentially
malignant. There is major concern as to the number of similar
prescriptions that are currently active, and how many other seri-
ous adverse reactions remain unrecorded.
References
1.
Lean M, Finer N. ABC of obesity. Management: part II-drugs.
Br Med
J
2006;
333
: 794–797.
2.
Florentin M, Liberopoulos EN,
et al
. Sibutramine-associated adverse
effects: a practical guide for its safe use.
Obes Rev
2008;
9
: 378–387.
3.
Sayin T, Guldal M. Sibutramine: possible cause of a reversible cardio-
myopathy.
Int J Cardiol
2005;
99
(3): 481–482.
4.
Advisory: Health Canada investigates safety of Meridia (sibutramine).
Ottawa: Health Canada; 2002 Mar 27. Available: http:/www.hc-sc.
gc.ca/English/protection/warngins/2002/2002_21e/htm.
5.
Dietel M. Sibutramine warning: hypertension and cardiac arrhythmias
reported.
Obes Surg
2002;
12
: 422.
6.
Ernest D. Sibutramine-associated QT interval prolongation and cardiac
arrest.
Ann Pharmcother
2008;
42
(10): 1514–1517.
7.
Natural Medicines Comprehensive Database. Stockton, CA 95208,
Therapeutic Research Faculty. 2008:203–205.
8.
MIMS Desk Reference
2010;
45
: 41–43.
9.
James WPT, Caterson ID,
et al
. Effect of sibutramine on cardiovascu-
lar outcomes in overweight and obese subjects.
N Engl J Med
2010;
363
(10): 905–917.
10. Abbott laboratories. Press release. October 2010.
.
com/global/url/pressRelease/en_US/60.5:5/Press_Release_0908.htm.
11. Scheen AJ. Cardiovascular risk-benefit profile of sibutramine.
Am J
Cardiovasc Drug
2010;
10
(5): 321–334.
