Correspondence Worsening myopathy associated with ezetimibe in a patient with McArdle disease

Transcription

Correspondence Worsening myopathy associated with ezetimibe in a patient with McArdle disease
Q J Med 2005; 98:461–464
Correspondence
Worsening myopathy associated
with ezetimibe in a patient with
McArdle disease
and aspirin was started. His lipid profile
slightly improved (Table 1) but remained above
recommended levels according to his estimated
cardiovascular risk score. Given the absence of
muscular symptoms and the low level of creatine
kinase (CK), we added ezetimibe 10 mg/day to his
therapy. For the first three months it was well
tolerated. CK levels slightly increased, with no
weakness or muscular cramps. The patient
remained stable for 20 weeks, when he started to
complain of fatigue, with impairment of exercise
tolerance. Four weeks later, CK levels dramatically
increased, and the patient eventually reported
slight myoglobinuria and severe weakness. No
drugs other than those scheduled had been taken,
and he had carefully avoided physical exertion
during this period. Ezetimibe was discontinued,
and the patient recovered uneventfully. CK levels
returned to previous values after 4 weeks, and the
patient remains stable 6 months later.
Table 1 Clinical and biochemical profile at baseline and development
Total cholesterol
HDL cholesterol
LDL cholesterol
Triglycerides
CK
Creatinine
Clinical
symptoms
Baseline
8 weeks
12 weeks
16 weeks
20 weeks
24 weeks
(ezetimibe
stopped)
28 weeks
287
34
199
271
837
0.80
No
232
35
160
183
3261
0.90
No
224
39
150
176
1047
0.90
No
240
38
162
201
4360
1.00
No
245
38
172
177
3100
1.00
Mild
weakness
237
38
163
181
21370
0.90
Severe
weakness
Myoglobinuria
316
36
NA
337
1123
0.90
Fatigue
Normal values: total cholesterol 110–200 mg/dl; triglycerides 45–200 mg/dl; HDL-c 40–80 mg/dl; LDL-c 60–155 mg/dl;
CK 25–190 U/l; creatinine 0.5–1.30 mg/dl. NA, not applicable.
The Author 2005. Published by Oxford University Press on behalf of the Association of Physicians.
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Sir,
McArdle disease (MD) is the most common
disorder of muscle carbohydrate metabolism,
caused by mutations in the gene that encodes
myophosphorylase.1 Only striated muscles are
involved, hence the clinical picture of exercise
intolerance, muscle cramps and myoglobinuria
secondary to rhabdomyolysis. This predisposition
to rhabdomyolysis may exclude the use of certain
drugs in MD patients. Ezetimibe, an inhibitor of
intestinal cholesterol absorption, is well tolerated,
and no adverse muscular effects have been reported
to date.2
An overweight 45-year-old White man,
diagnosed with MD by biochemical profile and
muscular biopsy, with essential hypertension,
type 2 diabetes mellitus, hypercholesterolemia
and hypertryglyceridemia suffered a non-Q-wave
myocardial infarction. Treatment with low fat
and low calorie diet, insulin, ramipril, bisoprolol
462
Correspondence
Myotoxicity is a well known side-effect of
statins, with a reported incidence of 1–7%.3 No
cases of rhabdomyolysis due to monotherapy
with ezetimibe have been described. However,
myopathy triggered by ezetimibe in patients
taking statins has been documented in two
patients.4 Although MD is a known cause of
rhabdomyolysis, the present case strongly suggests
that myotoxicity may be elicited by ezetimibe,
and poses the question of whether ezetimibe may
trigger muscular damage by mechanisms that are
presently unknown.
J. Perez-Calvo
Servicio de Medicina Interna
Hospital Clinico Universitario ‘‘Lozana Blesa’’
Zaragoza
Spain
F. Civeira-Murillo
Hospital Universitario ‘Miguel Servet’
Zaragoza
Spain
References
1. Lebo RV, Gorin F, Fletterick RJ, Kao FT, Cheung MC,
Bruce BD, et al. High-resolution chromosome sorting
and DNA spot-blot analysis assign McArdle’s syndrome in
chromosome 11. Science 1984; 225:57–9.
2. Bays HE, Moore PB, Drehobl MA, Rosenblatt S, Coth PD,
Dujovne CA, et al. Effectiveness and tolerability of ezetimibe
in patients with primary hypercholesterolemia: pooled analysis
of two phase studies. Clin Ther 2001; 23:1209–30.
3. Evans M, Rees A. The myotoxicity of statins. Curr Opin Lipidol
2002; 13:415–20.
4. Fux R, Mo¨rike K, Gundel UF, Hartmann R, Gleiter CH.
Ezetimibe and statin associated myopathy. Ann Intern Med
2004; 40:671–2.
doi:10.1093/qjmed/hci074
Discordant public and professional
perceptions on transparency in
healthcare
Sir,
Transparency is becoming a major issue in healthcare.1,2 Recent work shows substantial differences
between views of physicians and those of the public
Figure 1. Effect of a disclosure policy upon hospital
image, as perceived by the public and by physicians.
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Ana Cabello
Departamento de Anatomı´a Patolo´gica
Hospital Universitario ‘12 de Octubre’
Madrid
Spain
e-mail: mibh-jperez@hcu-lblesa.es
on medical errors:3 while the public views open
reporting as a very effective way of reducing errors,
physicians prefer confidentiality. We conducted a
survey to evaluate the potential contribution of a
disclosure policy to hospital image. Our findings
shed additional light on the discordance of opinions
between physicians and the public.
We conducted a phone survey (in Hebrew,
Russian and Arabic) of a representative sample
of the Israeli public (n ¼ 570) using random-dial
software. Respondents were asked to predict the
effects of a transparency policy upon public image
of hospitals and doctors, and also to what extent
physicians report mistakes.
In addition, we conducted 115 face-to-face
interviews of physicians with questions similar
to those of the public survey, in three major
teaching hospitals (two from Israel, one from the
US). They included 53 residents, 54 attending
physicians (from internal medicine, surgery and
gynecology), six department heads and two hospital
directors.
The majority of the public indicated that an
open disclosure policy would enhance the image
of hospitals (Figure 1). By contrast, a majority of
physicians predicted that disclosing mistakes would
damage the image of the hospital (p50.001 vs.
the public). American and Israeli physicians had
similar distribution of opinions.
Since Israel has a markedly heterogeneous
population, we examined whether ethnic or social
groups might have different answers. In all subgroups, including Russians, Arabs, and people with
low or high levels of education, the majority
consistently responded that transparency would
benefit hospital image.
Both the public and physicians thought that
disclosure to patients of individual mistakes by