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.