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28
VOLUME 9 NUMBER 1 • MARCH 2012
EVIDENCE IN PRACTICE
SA JOURNAL OF DIABETES & VASCULAR DISEASE
Rivaroxaban reduces stroke in atrial fibrillation
R
ivaroxaban, a direct factor Xa inhibitor, may
provide more consistent and predictable
anticoagulation than warfarin in patients with
atrial fibrillation (AF) who are at increased risk
of stroke.
The ROCKET AF (Rivaroxaban Once Daily
Oral Direct Factor Xa Inhibition Compared
with Vitamin K Antagonism for Prevention of
Stroke and Embolism Trial in Atrial Fibrillation)
was a double-blind multicentre trial in which
14 264 patients with non-valvular AF at
increased risk for stroke were randomly
assigned to treatment with rivaroxaban 20 mg
or dose-adjusted warfarin.
The study demonstrated that rivaroxaban
was non-inferior to warfarin in prevention of
stroke or systemic embolism. In the primary
analysis, the primary endpoint of ischaemic/
SAJDVD recommended action
Rivaroxaban may provide an oral alternative to war-
farin in the prevention of stroke in patients with AF.
It is not currently licensed in Europe for this indica-
tion. Xarelto
®
(rivaroxaban) is licensed for prevention
of venous thromboembolism in adults undergoing
elective hip or knee replacement surgery.
Reference
Patel M, Mahaffey K, Garg J,
et al.
Rivaroxaban
versus warfarin in nonvalvular atrial fibrillation.
N Engl J Med
2011; published online 10 August,
10.1056/NEJMoa1009638.
PRIMARY ENDPOINT IN INTENTION-TO-TREAT POPULATION
Rivaroxaban
Warfarin
patients (
n
) Events (
n
) Event rate* patients (
n
) Events (
n
) Event rate* HR (
p
value)
7 081
269
2.1
7 090
306
2.4
0.88 (0.75–
1.03)
p
< 0.001
*
n
/100 patient-years
haemorrhagic stroke or systemic embolism
occurred in 188 patients in the rivaroxaban
group (1.7% per year) and in 241 in the
warfarin group (2.2% per year) (hazard ratio
[HR] in the rivaroxaban group, 0.79; 95% CI,
0.66 to 0.96;
p
< 0.001 for non-inferiority).
In the intention-to-treat analysis, the primary
endpoint occurred in 269 patients in the
rivaroxaban group (2.1% per year) and in 306
patients in the warfarin group (2.4% per year)
(HR 0.88; 95% CI: 0.74–1.03;
p
< 0.001 for
non-inferiority;
p
= 0.12 for superiority).
There was no significant between-group
difference in the riskofmajor bleedingalthough
intracranial and fatal bleeding occurred less
frequently in the rivaroxaban group. Major
and non-major clinically relevant bleeding
occurred in 1 475 patients in the rivaroxaban
group (14.9% per year) and in 1 449 in the
warfarin group (14.5% per year) (HR 1.03;
95%CI: 0.96 –1.11;
p
= 0.44), with significant
reductions in intracranial haemorrhage (0.5%
vs 0.7%,
p
= 0.02) and fatal bleeding (0.2% vs
0.5%,
p
= 0.003) in the rivaroxaban group.
Rivaroxaban is currently licensed for pre-
vention of venous thromboembolism in adults
undergoing elective hip or knee replacement
surgery.
Originally from
PCCJ
2011;
4
(4): 144.
Metformin usage may protect women against pancreatic cancer
SAJDVD recommended action
Extended-release metformin, which also
reduces gastrointestinal side effects and
improves patient adherence,
3
could be
considered earlier for at-risk women
with a clinical history predisposing to the
development of type 2 diabetes, based
also on reducing cancer risk.
I
n a case–control study of 2 800 patients
with newly diagnosed pancreatic cancer,
the risk of developing pancreatic cancer was
significantly reduced in women receiving
metformin therapy for a few years.
1
Pancreatic cancer is relatively rare as far
as cancers go, but it progresses quickly. Most
people do not survive more than a couple
of years after diagnosis. Research has sug-
gested that people with pancreatic cancer
may have an increased risk of diabetes, but
it is unclear how diabetes and the drugs
used to treat it may affect pancreatic cancer
risks in previously cancer-free people.
To help answer that question, Dr Chris-
toph Meier of the University Hospital, Basel
in Switzerland and his colleagues consulted
a database of more than eight million people
in the UK, including about 2 800 who were
diagnosed with pancreatic cancer between
1995 and 2009. For each of those people,
they found another six of the same age and
gender that didn’t have pancreatic cancer,
to serve as a comparison group.
Using records from primary-care doc-
tors, the researchers determined how many
people in the pancreatic cancer and cancer-
free groups had previously been diagnosed
with diabetes and were on an antidiabetes
drug, such as metformin or sulfonylureas,
which included glimepiride and glyburide.
One in nine people with pancreatic
cancer had a prior diagnosis of diabetes,
compared to about one in 12 in the cancer-
free comparison group. According to their
medical records, 2% of people with pan-
creatic cancer had been taking metformin
long-term before they were diagnosed,
compared to 1.6% of the group without
cancer – a difference that could have been
due to chance.
But when the researchers separated the
records by gender, they found that signifi-
cantly fewer women with a new diagnosis
of pancreatic cancer had been taking met-
formin for at least a few years, compared
to cancer-free women. That was after the
researchers had already taken into account
whether women were overweight or obese
and if they smoked or drank alcohol.
The association in one gender but not
the other was ‘somewhat unexpected’,
according to Meier’s team, and there is no
clear biology-based way to explain why met-
formin might help protect women against
pancreatic cancer, but not men.
The findings were reversed for insulin
and sulfonylureas in the study population.
Significantly more people with pancreatic
cancer had a history of long-term use of
those drugs than cancer-free people.
Importantly, metformin is the first-line
oral medication recommended for type 2
diabetes. A recent review of two clinical
trials using metformin has shown the poten-
tial of using higher doses of metformin to
improve control in diabetic patients without
increasing gastrointestinal effects.
2
References
Bodmer,
1.
et al
. Use of antidiabetic agents and the risk
of pancreatic cancer: a case-control analysis.
Am J
Gastroenterol
, online 31 Jan 2012.
Hirst J, Farmer A, Ali R, Roberts NW, Stevens RJ.
2.
Quantifying the effect of metformin treatment and
dose on glycaemic control.
Diabetes Care
2012;
35
:
446–454.
Jabbour S,
3.
et al
. Extended release metformin –
increased GI tolerability, with once-daily dosage
– improve patient adherence – increase glucose
control.
Postgrad Med
2011;
123
(1): 15–23.