Discussion
Our study showed that in a large real-world cohort of aspirin users,
nearly one-fourth of the patients were receiving the drug for primary
prevention. The other main findings of our study were: 1- female
patients were more likely to be prescribed aspirin for primary
prevention compared to males; 2- aspirin was prescribed more often for
primary prevention than secondary prevention by specialists other than
the cardiologists and cardiovascular surgeons; 3- the rate of
inappropriate use of aspirin was high according to both ESC and USPTF
guidelines in the real-world practice; 4- independent predictors of
inappropriate aspirin use were female sex, oral anticoagulant use and
heart failure in primary prevention patients and older age, smoking,
hypertension, diabetes mellitus were associated with appropriate use of
aspirin.
Although aspirin has been used in the secondary prevention of
atherosclerotic events for more than 40 years (16), it has acquired a
negative image in primary prevention trials which showed that aspirin
did not reduce the overall mortality and did not have a net benefit
(10-12).
However, there are different recommendations between the European and
American guidelines regarding the use of aspirin in primary prevention.
The ESC guidelines recommended that aspirin should not be used for
primary prevention and subjects without clinical manifestations of CVD
should not take aspirin (class III, level A) (6).
The USPTF guidelines recommended that low-dose aspirin might be
considered in persons of 40 to 70 years of age who were at higher CVD
risk but not at increased bleeding risk (class IIb, level A), whereas it
should not be routinely administered in subjects aged >70
years (class III, level B) and should be avoided in subjects of any age
at increased risk of bleeding (class III, level C) (8). The presence of
such differences between the guidelines usually leads to physicians
having different treatment recommendations for patients without overt
CVD. However, indications and the appropriateness of aspirin use were
not well studied among Turkish patients. In the awareness, efficacy,
safety, and time in the therapeutic range of warfarin in the Turkish
population study (WARFARIN-TR) all consecutive patients using warfarin
were enrolled to evaluate the prevalence of the inappropriate
combination of aspirin and warfarin therapy (17). Although performed on
a very different patient population, the WARFARIN-TR study revealed that
one-fifth of patients who receive warfarin were receiving aspirin
inappropriately (17).
Data is very limited about patterns of inappropriate aspirin use in
Turkey but studies from Europe (18) and the US (19,20) have previously
documented overutilization of aspirin for primary prevention. Manes and
colleagues screened 20,599 patients in Italy and determined 400 patients
were on treatment with aspirin for primary prevention (18). The authors
found an overprescription of aspirin in 18% of the 400 patients. In a
cross-sectional study, individuals aged 30–79 years in the Marshfield
Epidemiologic Study Area were analyzed in the US (19). This study showed
that 19% of the 16,922 individuals who were not clinically indicated
for aspirin therapy for primary CVD were regular aspirin users (19). In
the last study, 68,808 patients receiving aspirin for primary prevention
were assessed in the US and inappropriate aspirin use frequency was
detected in 11.6% of the study cohort (20). However, all of these
studies performed before the publication of large randomized clinical
trials (10-12) examining the use of aspirin in primary prevention, and
all of these studies used different definitions for inappropriate
aspirin use such as a 10- year risk of a CVD event <6% or a
cardiovascular risk <1.0 event/100 patients/year. In our
study, we used the definitions of current guidelines and found that
inappropriate aspirin use frequency was 100% according to ESC and 71%
according to USPTF guidelines. The current study also showed that 56%
of the primary prevention group were female. (The current study is
comprised of 56% female in the primary prevention group.) We also
detected that aspirin was usually preferred and initiated by specialists
other than cardiologists and cardiovascular surgeons in the primary
prevention group.
Prevalence of aspirin use in primary prevention of cardiovascular
disease was found 23.4% among adults 40 years or older in the National
Health Interview Survey from the US. Of those 22.8% were using aspirin
without a physician’s recommendation. Of note older age, male sex, and
cardiovascular risk factors (hypertension, hyperlipidemia, diabetes, and
smoking) were statistically significantly associated with aspirin use in
this study (21). Similarly, our study showed female sex, oral
anticoagulant use and heart failure were independent predictors of
inappropriate aspirin use, and older age, smoking, hypertension,
diabetes mellitus were associated with appropriate use of aspirin.
The results of the ASSOS study revealed the overuse of aspirin in
low-risk patients despite the recent introduction of randomized
controlled trials and international guidelines, suggesting the need for
improved management of patients who had no overt CVD.