CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 6, November/December 2010
338
AFRICA
Opinions in Hypertension Management
ARBs and risk of cancer: international and South African expert comment
The suggestion from a recent meta-anal-
ysis that angiotensin receptor blockers
(ARBs) are associated with an increase
in new cancer occurrence but not
cancer deaths,
1
has resulted in the initia-
tion of a safety review of this class of
drugs by both the FDA (Federal Drug
Administration) and the EMA (European
Medicines Authority) in accordance with
good regulatory practice. This was also
advocated by Dr Steve Nissen in his edito-
rial comment.
2
In the interim, a review of
the published meta-analysis plus input
from Boehringer-Ingelheim is pertinent to
clinical practice.
Meta-analysis of randomised
control trials
1
This meta-analysis pooled the published
randomised, controlled trials of ARBs
and found that ARB use may be associ-
ated with a modest increased risk of new
cancers – predominantly lung cancer.
Patients who were randomly assigned to
receive ARBs had an increased risk of
new cancer occurrence compared with
patients in the control groups (7.2 vs 6.0%,
risk ratio 1.08, 95% CI, 1.01–1.15). When
analysis was limited to those trials (LIFE,
ONTARGET and TRANSCEND) where
cancer was a pre-specified endpoint, the
risk ratio was 1.11 (95% CI, 1.04–1.18,
p
=
0.001). The authors concluded that
the findings of the meta-analysis warrant
further investigation.
The meta-analysis reviewed 60 trials
and included published and available
FDA data from nine different trials (Table
1) to assess overall cancer risk and risk
of specific solid-organ cancers associated
with ARBs plus ACE inhibitor therapy,
compared with ACE inhibitors alone.
Cancer was a pre-specified endpoint of
special interest in three of the five trials
that included new cancer data for analysis
of cancer occurrence (LIFE, ONTARGET
and TRANSCEND).
In the ONTARGET andTRANSCEND
trials, information on the occurrence of
malignancies was also collected prospec-
tively in more detail than usual for trials
of cardiovascular outcomes, thereby plac-
ing the spotlight on telmisartan which
was the study drug in 30 014 (85.7%)
of the ARB-treated patients included in
the meta-analysis. The association of
ARBs with the occurrence of solid-organ
cancers, new lung, prostate and breast
cancer from the meta-analysis is summa-
rised in Table 2.
Comment from Boehringer
Ingelheim
Boehringer-Ingelheim commented that
peer-reviewed meta-analyses of aggregate
published data such as that of Sipahi
et
al
.
1
have their appropriate place in scien-
tific research. However, these publica-
tions have well-recognised limitations,
including the following:
•
the analyses did not include the indi-
vidual patient data for any of the trials
•
the trials were not designed to explore
cancer outcomes
•
the adjudication of cancer diagnoses
was not uniform among included stud-
ies
•
the analyses did not consider the laten-
cy for the malignancies
TABLE 1. RANDOMISED CONTROLLED TRIALS OFANGIOTENSIN RECEPTOR BLOCKERS THAT REPORTED CANCER DATA
Condition studied
Mean or
median
duration,
years
Number
of
patients Study drug
Control
History of cancer
at baseline (%)
Study
drug Control
Trials with data on new cancer, new specific solid-organ cancers, and cancer death
LIFE (2002)
Hypertension
4.8 9 193 Losartan up to 100 mg (
n
=
4605)
Atenolol up to 100 mg
(
n
=
4588)
NA NA
ONTARGET
(2008)
Cardiovascular disease* or
diabetes with end-organ damage
4.7 25 620 Telmisartan 80 mg (
n
=
8542) or Telmisar-
tan 80 mg
+
ramipril 5 mg (
n
=
8502)
Ramipril 5 mg
(
n
=
8576)
6.3
6.3
TRANSCEND
(2008)
ACE inhibitor-intolerant patients
with cardiovascular disease* or
diabetes, with end-organ damage
4.7 5 926 Telmisartan 80 mg (
n
=
2954)
Placebo (
n
=
2972)
4.9
4.9
PROFESS (2008) Recent (
<
90 days) ischaemic
stroke
2.5 20 332 Telmisartan 80 mg (
n
=
10146)
Placebo (
n
=
10186)
NA NA
Trials with data on new specific solid-organ cancers and cancer death
CHARM-Overall
programme (2003)
Heart failure
3.1 7 599 Candesartan up to 32 mg (
n
=
3803)
Placebo (
n
=
3796)
7.1
6.4
Trials with new-cancer data only
TROPHY (2006) Pre-hypertension
3.6
787 Candesatran 16 mg (
n
=
391)
Placebo (
n
=
381)
NA NA
Trials with cancer death data only
VAL-HEFT
(2001)
Heart failure
1.9 5 010 Valsartan up to 120 mg twice daily
(
n
=
2511)
Placebo (
n
=
2 499)
NA NA
OPTIMAAL
(2002)
Acute myocardial infarction
2.7 5 477 Losartan up to 50 mg daily (
n
=
2 744)
Captopril up to 50 mg
three times daily
NA NA
VALIANT (2003) Acute myocardial infarction
2.1 14 626 Valsartan up to 80 mg twice daily
(
n
=
4 885) or Valsartan up to 40 mg twice
daily
+
captopril up to 25 mg three times
daily (
n
=
4 862)
Captopril up to 25 mg
three times daily
(
n
=
4 879)
NA NA
ACE
=
angiotensin converting enzyme. NA
=
not available. *Includes coronary, peripheral, or cerebrovascular disease
