Transcript Background and Objective

Background and Objective
• In the recently reported Simvastatin and Ezetimibe
in Aortic Stenosis (SEAS) trial, the combination of
ezetimibe/simvastatin (E/S) was associated with a
significantly increased risk of cancer compared to
placebo, causing widespread public concern.
• We examined the rates of cancer adverse event
reports filed with the US Food and Drug
Administration (FDA) of patients on ezetimibe or
E/S, and compared these to reports with other
potent cholesterol-lowering drugs.
Alsheikh-Ali and Karas JCL 3(2):138-142, 2009
Methods
• We tabulated all adverse event reports listing
‘‘cancer’’ or ‘‘malignancy’’ filed with the FDA (July
2004 to March 2008) of patients taking ezetimibe
or E/S, and compared those to reports of patients
taking simvastatin, atorvastatin, or rosuvastatin.
• We calculated rates for such reports per million
prescriptions. A secondary analysis examined
cancer reports as a proportion of all reported
adverse events for each medication.
Alsheikh-Ali and Karas JCL 3(2):138-142, 2009
Results
• Prescriptions for all drugs totaled 559 million
(approximately 52 and 55 million prescriptions of
ezetimibe and E/S, respectively), and cancer
adverse event reports totaled 2334.
• There were 2.9 and 1.3 cancer-associated adverse
event reports per million ezetimibe or E/S
prescriptions, respectively, compared to a range of
3.1 to 5.1 per million prescriptions for the other
drugs.
Alsheikh-Ali and Karas JCL 3(2):138-142, 2009
Results
• Findings were similar when only reports listing the
drug as ‘‘suspect’’ were considered.
• The proportions of reports listing cancer relative to
all adverse event reports were 2.0% and 1.9% for
ezetimibe and E/S, respectively, compared to a
range of 1.3% to 3.9% for the other drugs.
Alsheikh-Ali and Karas JCL 3(2):138-142, 2009
Results
Table 1: Characteristics of cancer associated adverse event reports.
Ezetimibe
Simvastatin
Ezetimibe/
Simvastatin
Atorvastatin
Rosuvastatin
Total prescriptions (millions)
52.1
139.2
55.1
266.5
45.7
Total cancer adverse event
reports
151
705
73
1264
141
65 ± 11
67 ± 10
64 ± 11
66 ± 11
66 ± 11
Gender (% male)
43
54
49
52
54
Fatal outcome (%)
6
21
10
20
11
Breast
15
11
5
15
10
Lung
14
17
18
15
10
GI
20
22
16
16
23
Renal
9
7
15
8
11
Skin
11
11
11
8
7
Blood
16
21
21
19
28
Other
15
11
14
19
11
Age
Cancer site (%)
Alsheikh-Ali and Karas JCL 3(2):138-142, 2009
Results
*P < 0.01 versus ezetimibe/simvastatin
†P < 0.01 versus ezetimibe
Alsheikh-Ali and Karas JCL 3(2):138-142, 2009
Results
*P < 0.01 versus ezetimibe/simvastatin
†P < 0.01 versus ezetimibe
Alsheikh-Ali and Karas JCL 3(2):138-142, 2009
Results
Table 2: Rates of cancer associated adverse event reports in patients treated
with the combination ezetimibe/simvastatin and other potent cholesterol
lowering drugs (rate per million prescriptions).
Ezetimibe
Simvastatin
Ezetimibe/
Simvastatin
Atorvastatin
Rosuvastatin
All cancer adverse event
reports
2.9
5.1
1.3
4.7
3.1
Suspect only
0.5
0.7
0.3
1.7
1.4
Non-suspect only
2.4
4.4
1.0
3.0
1.7
Excluding first year of E/S
approval in US (7/20053/2008)
3.1
4.9
1.4
4.9
2.9
Excluding first year of E/S
approval in US and 2008
(7/2005-12/2007)
3.0
5.0
1.4
4.8
2.8
Alsheikh-Ali and Karas JCL 3(2):138-142, 2009
Conclusions
• This large-scale post-marketing analysis of
reported adverse events does not support
that ezetimibe or E/S increase the risk of
cancer.
Alsheikh-Ali and Karas JCL 3(2):138-142, 2009