The prevalence and correlates of low dose aspirin use for cardiovascular prevention among patients with diabetes mellitus at the Jimma Medical Center, Ethiopia

¹Department of Internal Medicine, Jimma University, Jimma, Ethiopia, ²Department of Internal Medicine, Adama Hospital Medical college, Adama, Ethiopia, ³Department of Internal Medicine, Mettu Karl Hospital, Mettu University, Mettu, Ethiopia, ⁴School of Pharmacy, College of Public Health and Medical Sciences, Jimma University, Jimma, Ethiopia, ⁵College of Public Health and Medical Sciences, Jimma University, Jimma, Ethiopia

^&Corresponding author
Kedir Negesso Tukeni, Department of Internal Medicine, Jimma University, Jimma, Ethiopia

Introduction    

The burden of cardiovascular disease (CVD) is substantial in patients with diabetes mellitus (DM), who have a two-to four-fold increase in the incidence of cardiovascular events compared with age- and sex-matched, non-diabetic persons [1]. The prevalence of DM increased from 108 million (4.7%) in 1980 to 425 million (8.5%) in 2017, and it is estimated to be 629 million by 2045 [2]. Morbidity and mortality of CVD in patients with type 2 DM have a risk of death from cardiovascular causes that is two to six times that among persons without DM, and among white Americans the age-adjusted prevalence of coronary heart disease is twice as high among those with type 2 DM as among those without DM [3]. Diabetes-related CVD complications are on the rise, that associated with cardiovascular risk factors. Coronary heart disease (CHD) may affect 5% to 8% of type 2 diabetic patients and cardiomyopathies, up to 50% of all patients. Close to 15% of patients with stroke have diabetes, and up to 5% of diabetic patients present with cerebrovascular accidents at diagnosis [4].

In 2015, the Ethiopian Diabetes Association (EDA) and International Diabetic Federation (IDF) reported almost the same number of people living with diabetes in the country, 1.33 million and 1.30 million respectively [5]. Various studies were conducted to assess the prevalence of CVD in patients with DM in Ethiopia. The overall prevalence of CVD among T2DM patients was 42.51% in Harari regional state of Ethiopia [6], 15.29% in Jimma Medical Center (JMC) [7]. A systematic review conducted from institutional and community-based studies with 5% prevalence of CVD in patients with DM reported [8].

Aspirin has been shown to be effective in reducing cardiovascular morbidity and mortality in high-risk patients with previous myocardial infraction (MI) or stroke (secondary prevention) [9]. In the primary prevention trials, aspirin allocation yielded a 12% proportional reduction in serious vascular events [10]. With its therapeutic dosage of 75-162 mg/day may be considered as a primary prevention strategy in those with Type 1 or Type 2 diabetes who are at increased cardiovascular risk [11]. However, its net benefit in primary prevention among patients with no previous cardiovascular events is more controversial both for patients with diabetes and for patients without diabetes [12]. An association between increases in aspirin dose and risk of adverse events has been confirmed in multiple studies, whereas no such dose relationship has been identified for efficacy. This suggests that following the rapid, acute inhibition of platelet COX-1 with 160 to 325 mg of aspirin, every effort should be made to minimize the long-term dosage [13]. Aspirin has been considered underutilized despite its beneficial effects in primary and secondary prevention of CVD in patients with diabetes mellitus [14]. Therefore, this paper assessed the prevalence of low dose aspirin utilization and its associated factors in patients with DM at Jimma Medical Center, Ethiopia.

Methods     

Study design and setting: a prospective observational hospital-based study was conducted at Jimma Medical Center, Ethiopia, from October 1, 2020 to November 15, 2020. Jimma Medical Center is a tertiary teaching hospital located in Jimma Town, Oromia region of Ethiopia, serving a population of over 20 million population catchment areas. The medical center has over 1500 healthcare providers, serving about 160,000 outpatients, 11,000 emergency cases and more than 4700 deliveries per year. The diabetic clinic is among the follow-up clinics serving for about 1300 patients with diabetes. The hospital provides coronary care services, dialysis and higher imaging services including computed tomography (CT) and magnetic resonance imaging (MRI).

Data collection: a structured data collection format, which was tested for consistency prior to the data collection, was used including the socio-demographic characteristics (age, sex, chart number, marital status, level of education, monthly income, and area of residence) and clinical profiles such as duration of DM, history of CVD and co-administered medications. The charts of the study population were collected and reviewed after cross-checking chart number with that on the registration book. Additionally, patients were also interviewed to get the missed data from the charts. The data collectors were used personal protective equipment like alcohol-based hand sanitizer, and face mask to reduce the risk of transmission of Coronavirus disease (COVID-19) during data collection.

Data analysis: data were analyzed using EpiData manager version 4.6 and then STATA version 16.0. Demographic characteristics of the study subjects were analyzed descriptively. Categorical data was analyzed using frequencies (n) and percentages (%) and represented in graphs and pie charts. Continuous data were analyzed using mean (SD) for normally distributed data or median (IQR) for skewed data. Chi-square, Fischer's exact, students were used in bi-variate analysis while binary logistic was used to conduct multivariate analysis. Fischer's exact was used when cell frequency was less than five (n<5) while Chi-square test was used for cell frequency (n>5). Significance level required was <0.05. Odds ratio was used to show direction of association between the independent and dependent variables.

Study limitation: included that patient may not properly remember their age and this may change the recommendations for use of aspirin as the indication for primary prevention of Atherosclerotic cardiovascular disease (ASCVD) is dependent on age. Moreover, we used a cross-sectional observational study design and cannot draw conclusions related to temporal use of low dose aspirin of any observed associations.

Ethical consideration: ethical clearance was obtained from the Institutional Review Board (IRB) of the Institute of Health, Jimma University. Written informed consent was obtained from the study participants before starting the data collection process. All patients were granted the right to withdraw from the research at any time. The confidentiality and privacy of patients were assured throughout the study period by removing the identifiers from the data collection tools using different codes. Neither the data records nor the extracted data were used for any other purpose.

Results     

Socio-demographic characteristics: among 388 patients with diabetes included in the study, 268 (69.1%) of the participants were male, and the mean age was 48.8 [48.2, 51.4] years. The majority of the patients were from the rural side of Jimma, Ethiopia, and about 28.6% (111) had no formal education (Table 1).

Clinical characteristics: about a third (30.9%) of the patients were having 5-9 years history of diabetes mellitus, while nearly half (48.7%) patients had a history of hypertension. About 27 (6.9%) of the patients were having history of heart attack, ischemic stroke or peripheral arterial disease (Table 2).

Prevalence and pattern of low dose aspirin utilization: among patients with diabetes on follow up, 183 (47.2%) were utilizing low dose aspirin. The largest proportions (24.2%) of participants taking low dose aspirin were in the age group of 50-64 years. Among those taking low dose aspirin, male accounts 35% (136) and most of those patients with hypertension, about 32.2%, were using low dose aspirin (Table 3). In general, among 388 patients with diabetes, 80 (20.6%) of them had indication to use low dose aspirin for the primary and secondary prevention of cardiovascular events. However, only 59 (73.8%) of patients were using it appropriately. From the 183 patients provided with low dose aspirin, 103 (56.3%) were provided without clear indication as per active international guidelines. In the subgroup of patients with diabetes and having indication for secondary prevention of cardiovascular events, 7 (25.9%) of them were not provided with the medication (Table 4).

Prevalence and correlates of inappropriate utilization of low dose aspirin: reasons for not using low dose aspirin in indicated cases: among patients with diabetes mellitus with low dose aspirin is indicated but not taking, the most commonly cited reason is lack of prescribing by the healthcare providers, while other factors like upper gastrointestinal problems, availability of the drug, cost of the medication (affordability), and bleeding related to the drug are also commonly cited (Figure 1). Duration of the diabetes Mellitus, age of the patients, presence or absence of lipid abnormalities, presence or absence of hypertension, and chronic kidney disease/albuminuria also affect the utilization of low dose aspirin after controlling other confounding effects. Accordingly, Patients who live 10–14 years with diabetes were six times more likely [AOR 6.25 (95% C.I. 2.33, 16.75)] to utilize a low dose aspirin as compared to those living with diabetes for less than 2 years. In terms of age group, those in the age group of 40–49 years, 50–64 years, and 65 years above were 3.99, 7.28, and 8.51 more likely to utilize a low dose of aspirin as compared to those under 30 years of age respectively. Participants who have a history of hypertension were about twice more likely [AOR 1.97 (95% C.I 1.11, 3.50)] and those who have dyslipidemia were three times more likely [AOR 3.07 (95% C.I 1.60, 5.90)] to utilize a low dose aspirin compared to their counterparts (Table 5).

Discussion     

This study was conducted on 388 patients with diabetes to assess the use of low dose aspirin and correlates for primary and secondary prevention of cardiovascular disease among patients with diabetes at Jimma Medical Center, Ethiopia, from October to November 2020. Of the all-study patients with diabetes, 188 (47.2 %) of them use low dose aspirin. This is a higher rate than the findings in the analysis of the National Health and Nutrition Examination Survey 2011-2012 conducted in the U.S. to examine the use of aspirin for CVD prevention that showed 40.9% reported being told by their physician to take aspirin, with 79.0% (31.6 % of the total) complying [15]. However, a study conducted in US to assess the use of aspirin in diabetes and non-diabetes participants shows a higher use of aspirin utilization among older adults (61.7%) than this study [16]. This is because of this study was conducted specifically among older patients with a higher risk and hence increased rate of indications that possibly increase the utilization of aspirin use. In China, aspirin utilization was 53.5% which is a higher than this study [17].

Among the 27 patients with diabetes and Atherosclerotic cardiovascular diseases (ASCVD), 20 (74.1%) were on low dose aspirin; which is comparable with the study conducted in US to assess recent self-reported regular aspirin use among adults 35 years or older with diabetes in 2001, which was 74.2% [18]. From this study, 21.3% of patients with diabetes had inappropriate use of low dose aspirin for primary prevention, and this is lower than the study conducted in Turkey, which showed 59.2% of patients were using the medicine inappropriately [19]. However, the inappropriate utilization of aspirin for primary prevention is nearly doubled when compared with the study conducted in US, which was 11.6% [20]. As per ADA (American Diabetic Association) 2020 guideline [12], among the 388 study patients with diabetes, aspirin was indicated for 80 (20.6%) of the patients and 21 (26.2%) of them were not using it, while in 59 (15.2%) of the cases, it was indicated and was prescribed. This result is higher when compared to the study conducted in Saudi Arabia, which showed that from 312 patients, aspirin was indicated for 17.0%, but it was not prescribed; while it was indicated and prescribed in 36.2% of the cases [1]. When compared to the study conducted in India [21], 11% of patients were prescribed with an indication for a primary prevention which is similar with this study, which showed 10.6%; however, 10% of the patients were not utilized despite indicated for a primary prevention, which is higher than this study (3.6%) and there was no documentation for the reasons not using aspirin while this study found that 55.2% of patients were reasoned out as “not prescribed”.

In this study, older age, longer duration of diabetes mellitus, dyslipidemia and hypertension were associated with more likely utilization of low dose aspirin. A similar study done in US, among both in low and high-risk individuals for primary and secondary prevention, higher age groups were more likely to utilize a low dose of aspirin as compared to their counterparts [AOR 5.29 (95% C.I. 3.64, 7.69)] [15] which is similar to this study as age group was found to be a significant predictor of using a low dose aspirin, [AOR 8.51 (95% C.I. 5.86, 13.85)]. The increase in the prevalence of aspirin use in older populations with diabetes over recent decades may be due to a multitude of factors. Before 2019, aspirin was recommended for older than 50 years without an upper cutoff age limit [22-24]. With the updated guideline of the ADA in 2019, aspirin use was discouraged for primary prevention in adults older than 70 years despite aspirin could be considered for patients with high CVD risk and low bleeding risk [12]. In the same year, the American College of Cardiology (ACC) and the American Heart Association (AHA) released updated guidelines that recommended against routine aspirin use for primary prevention in adults older than 70 years [25]. Duration of diabetes was significantly influencing low dose aspirin utilization. This could be due to detection of risk factors as indications to use low dose aspirin through time during follow-ups. Patients with a history of hypertension were about twice more likely to utilize a low dose of aspirin compared to non-hypertensive patients with diabetes. This is due to its potential increased risk factor for CVD. As study showed the effect of aspirin in patients with hypertension and diabetes mellitus, there was a 51% reduction in major cardiovascular events in target group ≤80 mm Hg compared with target group ≤90 mm Hg (p for trend=0·005) [26].

Conclusion     

About a fifth percent of patients with diabetes mellitus were utilizing low dose aspirin, despite only a quarter of them were having indications for prevention of cardiovascular diseases. Moreover, about a quarter of patients with diabetes mellitus were not prescribed for low dose aspirin despite there were indications as per active guidelines. Therefore, there is a need for healthcare providers to critically assess the need of low dose aspirin in patients with diabetes mellitus for the prevention of cardiovascular events.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Kedir Negesso Tukeni, Eyob Girma Abera and Nigatu Asfaw Regassa: contributed to conceptualization, design, investigation, analysis and write-up of the first draft. Kedir Negesso Tukeni, Ebrahim Umer Mohammed, Bedaso Negesso Tukeni and Eyob Girma Abera: participated in the design, data curation drafting, interpretation and edition of the data and supervision. Kedir Negesso Tukeni and Eyob Girma Abera: were involved in the design, supervision and edition of the manuscript. All authors reviewed and edited the manuscript and approved the final version of the manuscript.

Acknowledgments     

We are grateful to Jimma Medical Center Diabetic follow-up clinic staffs and other healthcare professionals working in the clinic for their kind cooperation throughout the study period.

Tables and figure     

Table 1: socio-demographic characteristics of patients with diabetes mellitus on follow up at Jimma Medical Center, Southwest Ethiopia, in 2020.

Table 2: clinical characteristics of patients with diabetes mellitus on follow-up at Jimma Medical Center diabetic clinic, Southwest Ethiopia, in 2020

Table 3: pattern of use of low dose aspirin use among patients with diabetics on follow up at Jimma Medical Center diabetic clinic, Southwest Ethiopia, in 2020

Table 4: client's adherence to American Diabetic Association (ADA) 2020 guidelines to use low dose aspirin

Table 5: a multi-variable logistic regression model of low dose aspirin use among patients with diabetics on follow up at Jimma Medical Center diabetic clinic, Southwest Ethiopia, in 2020

Figure 1: reason for not using low dose aspirin in indicated case in patients with diabetes mellitus

References