DRUG TRENDS
SA JOURNAL OF DIABETES & VASCULAR DISEASE
132
VOLUME 7 NUMBER 3 • SEPTEMBER 2010
Aspirin in primary prevention: focus on people with diabetes
A
n expert consensus view on the use of aspirin
in patients with diabetes has just been pub-
lished and provides an excellent overview of aspi-
rin trials in diabetic patients.
1
Reviewing all the evidence of aspirin in pri-
mary prevention, the consensus statement by
the American Diabetes Association, the Ameri-
can Heart Association and the American College
of Cardiology Foundation concludes that aspirin
has a significant effect on reducing cardiovascular
events (RRR of about 10%) and that the extent of
reduction is dependent on the underlying cardio-
vascular risk.
While consensus statements in general risk
introducing compromise, the recommendations
of these societies are clear. They point out that
further evidence from ongoing trials such as
ACCEPT D (Aspirin and simvastatin Combination
for Cardiovascular Events Prevention Trial in Dia-
betes) and ASCEND (A Study of Cardiovascular
Events iN Diabetes) may alter the consensus view.
Their recommendations are:
• Use low-dose (75–162 mg/day) aspirin for
prevention in adults with diabetes and no
previous history of vascular disease who are
at increased risk for cardiovascular disease
(CVD) (10-year risk of CVD events over 10%)
and who are not at increased risk for bleeding
(based on a history of previous gastrointestinal
bleeding or peptic ulcer disease or concurrent
use of other medications that increase bleed-
ing risk, such as NSAIDS or warfarin). Those
adults with diabetes at increased risk for CVD
include most men over the age of 50 and
women over 60 years who have one or more
of the following additional major risk factors:
smoking, hypertension, dyslipidaemia, family
history of premature CVD and albuminu-
ria (ACCF/AHA class IIa, level of evidence: B)
(ADA level of evidence: C).
• Aspirin should not be used for CVD preven-
tion in adults with diabetes at low CVD risk
(men under 50 years of age and women under
60 with no major additional CVD risk factors;
10-year CVD risk under 5%) as the poten-
tial adverse effects from bleeding offset the
potential benefits (ACCF/AHA class III, level of
evidence: C) (ADA level of evidence: C).
• Low-dose (75–162 mg/day) aspirin use for
prevention might be considered for those with
diabetes at intermediate CVD risk (younger
patients with one or more risk factors, or
older patients with no risk factors, or patients
with 10-year CVD risk of 5–10%) until further
research is available (ACCF/AHA class IIb, level
of evidence: C) (ADA level of evidence: E).
Importantly, the statement points out that car-
diovascular risk must be accurately defined and
also that blood pressure and lipid management,
and smoking cessation strategies should be intro-
duced first. This will reduce cardiovascular risk
and also the number of patients with diabetes
requiring aspirin therapy.
The recommendationnotes that not all diabetes
patients have high cardiovascular risk, as was pro-
posed inearlier guidelines, suchas theNCEP, 2001.
2
Preventing cardiovascular events
and stroke
Interestingly, the US Preventative Services Task
Force (USPSTF) recommendations on the benefits
and harm of aspirin for primary prevention of vas-
cular disease, including cardiovascular and cere-
brovascular disease, also noted that aspirin should
be used cautiously in women (whether diabetic or
not) under the age of 60 years at low risk (under
5%) as primary prevention.
3
The ADA/AHA/ACC
consensus recommendations regard the balance
of benefit and risk for aspirin usage in diabetic
men at low cardiovascular risk (less than 5%)
as being reached at a younger age of 50 years,
compared to the USPSTF calculation of reaching
a balanced benefit–risk for cardio- and cerebro-
vascular events for men under the age of 60 years
at 4 to 5% cardiovascular risk.
J Aalbers, Special Assignments Editor
1.
Pignone M, Alberts MJ, Colwell JA, Cushman M,
Inzucchi SE, Mukherjee D,
et al
.
J Am Coll Cardiol
2010; 55(25). Published online. Doi:10.1016/j.
jacc.2010.04.003.
2.
Expert panel on detection, evaluation and
treatment of high blood cholesterol in adults.
J Am
Med Assoc
2001;
285
: 2486–2497.
3.
US Prevention Services Task Force.
A Intern Med
2009;
150
(6): 396–413.
Erectile dysfunction and diabetes: a prelude to cardiovascular disease
E
rectile dysfunction (ED) occurs in 80% of dia-
betic men over 60 years of age, due to both
endothelial and neurological abnormalities. Early
and vigorous glucose control may prevent erectile
dysfunction. In addition, early statin use and the
use of phosphodiesterase type 5 (PDE5) inhibi-
tors may help to preserve the endothelial func-
tion in diabetic men, according to a recent expert
committee review of the worldwide literature
concerning erectile dysfunction, coronary artery
disease and diabetes.
1,2
The presence of erectile dysfunction in
younger diabetic men may point to increased risk
of coronary artery disease (CAD) and therefore
should be treated, while also aggressively lower-
ing other risk factors such as alcohol, smoking,
inactivity and overweight.
In a study of 2 306 diabetic men in China with
no clinical evidence of CAD (27% suffered from
ED at baseline), over a median course of four
years, ED was an independent predictor of CAD
with a hazard ratio (HR) of 1.58 after adjustment
for confounding factors.
3
In a second European study evaluating erectile
dysfunction as a predictor of major cardiovascular
events, the researchers also investigated which
other factors predicted cardiovascular events and
mortality. A group of 291 diabetic men with silent
CAD detected angiographically were followed up
for a period of four years.
The presence of erectile dysfunction, as
expected, was significantly related to an increased
risk of major cardiovascular events. Of more inter-
est was that in men with both CAD and ED, statin
and PDE5 use was associated with a lower risk of
major events. Statin use significantly reduced risk,
while use of PDE5 inhibitors approached signifi-
cance (HR 0.68; 95% CI: 1.46–1.01;
p
=
0.056).
In choosing which PDE5 inhibitor to use in
diabetic patients, vardenafil has been shown to
achieve a significantly higher success rate in dia-
betic men than its competitors.
1
Sildenafil and
tadalafil have shown an average success rate in
diabetic patients of 60 to 64% compared to pla-
cebo, whereas vardenafil has shown that erectile
function improved in 72% of diabetic patients
compared to placebo.
Vardenafil has a shorter half-life than sildena-
fil, which has a peak effect from one to 12 hours.
Vardenafil’s shorter half-life has advantages in the
therapeutic treatment of erectile dysfunction, but
has less value as a once-a-day preventative treat-
ment for endothelial dysfunction. It is normally
administered in 5-, 10- and 20-mg doses with a
recommended starting dose of 10 mg. Adverse
effects are generally mild; there is no impairment
of exercise ability in patients with stable CAD who
have been carefully assessed. None of the PDE5
inhibitors have been shown to increase myocar-
dial infarction rates.
In addition, PDE5 inhibitors provide benefit in
treating pulmonary hypertension and have shown
some encouraging results in heart failure, which
may contribute to their wider use in these patient
groups.
J Aalbers, Special Assignments Editor
1.
Gazzaruso C, Solerte SB, Pujia A, Coppola A,
Vezzoli M, Salvucci F,
et al
.
J Am Coll Cardiol
2008;
51
: 2040–2044.
2.
Jackson G, Montorsi P, Adams MA, Anis T, El-Sakka
A, Miner M,
et al
.
J Sex Med
2010;
7
: 1608–1626.
DOI:10.1111/j.1743-6109.2010.01779.x.
3.
Ma RC, So WY, Yang X, Yu LW, Kong AP, Ko GT,
et
al
.
J Am Coll Cardiol
2008;
51
: 2045–2050.
