The effect of socioeconomic disadvantage on prescription of guideline-recommended medications for patients with acute coronary syndrome: systematic review and meta-analysis

Acute coronary syndrome (ACS) is a high-risk form of coronary atherosclerosis, consisting of myocardial infarction (MI) and unstable angina (UA). About 1.4 million people are hospitalised with a diagnosis of ACS every year in the United States [1]; in Australia, more than 95,000 are hospitalised each year with a readmission rate within 6 months of about 20% [2, 3]. To reduce the risk of recurrence or death, recommended treatment guidelines for optimal treatment are in place [4‐7]. An important part of these guidelines is the prescription of recommended medications at discharge from hospital. The recommended medications include aspirin and antiplatelet, which prevent blood to clot; beta blocker and angiotensin co-enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB), which are blood pressure lowering medications; and statin/lipid lowering therapy, which are cholesterol lowering medications [8, 9]. These evidence-based medications have been proven to reduce the risk of mortality and major adverse cardiovascular events, with further risk reduction when used in combination, and are recommended to be taken long-term [4‐7, 10, 11]. However, studies suggest that there are social subgroups that receive optimal treatment less often [12‐16].

World Health Organisation (WHO) reports that social factors such as socioeconomic status (SES) can influence patients’ treatment of illness as well as health [17]. Previous studies found that patients with low SES have significantly higher risk of an outcome or death due to a chronic disease, including chronic obstructive pulmonary disease outcomes, cardiovascular disease [18‐20]. Similar results were found for ACS, where the lowest SES group had the highest rates of MI and death due to coronary heart disease [21]. When it seems appropriate for those with ACS and low SES to be treated more rigorously compared to those with high SES, some studies have reported that patients in the lowest SES group were disadvantaged in receiving some guideline recommended discharge medication prescriptions [12‐16]. However, there were also evidence suggesting that patients receive comparable rate of prescription across the SES groups [13‐15, 22, 23].

Therefore, to better understand whether the treatment gap exists between the SES groups in patients with ACS, we aimed to synthesise results from studies that reported on the effect of SES on discharge prescription of medications for patients with ACS.

Pre-specified methods for this systematic review were registered in the International prospective register of systematic reviews (PROSPERO) Registry (registration no.: CRD 42016048503). Studies were eligible for review if the participants were patients with a diagnosis of ACS, stratified by patients’ SES and the studies reported the rate or the odds of any of the prescription of guideline-recommended ACS medications (aspirin, antiplatelet, ACEi/ARB, beta blocker and/or statin/lipid-lowering therapy) at hospital discharge. Due to the nature of the question, only observational studies were included. There were no language or date restrictions. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used to report this systematic review [24].

Of 252 articles found from the initial search, 14 articles were assessed in full-text and seven articles met the eligibility criteria to be included in the systematic review (Fig. 1). The measures of SES included income, education, deprivation score and country income level (Table 1). Characteristics of the seven articles are shown in Table 1. Two of the studies analysed different medications from one dataset [12, 22]. One study focused on international variations, and countries were compared according to SES; in this instance, the outcomes for the country with the low/middle SES was compared to that with the high as stratified in the original article [18]. Four studies focused on population subgroups within regions and compared neighbourhoods within these regions [12, 14, 22, 23]. Two studies reported patient level SES [13, 16]. In total, the seven articles included ACS 41,462 patients in the lowest and highest SES groups together, of which 20,986 were from the lowest group. Of the total, 392 patients were stratified by country level income, and 127 of those were from the lowest income countries [15]. In regards to the outcomes reported, five articles examined the prescription of aspirin [12‐15, 23], five articles on beta blocker [12‐15, 23], three articles on ACE [12, 13, 15], three articles on lipid lowering therapy [15, 16, 22] and two articles on combination of medications [12, 15].

The current systematic review has assessed and analysed seven articles that compared the likelihood of prescription of guideline-recommended medications (aspirin, beta blocker, lipid-lowering therapy and ACEi) to ACS patients between the SES groups at hospital discharge. We found that individual/neighbourhood level SES had an effect on the prescription of beta blocker, statin and ACEi, but not aspirin. Beta blocker and statin were 16% and 20% less likely, respectively, to be prescribed to the lowest SES group than to the highest SES group. In contrast, ACEi was 13% more likely to be prescribed to patients in the lowest SES group compared to those in the highest SES group. The study that compared between the country level SES showed similar results, where the lowest SES group were less often prescribed beta blocker and lipid lowering therapy but more often prescribed ACEi than the highest SES group [15].

The opposing effect of SES on two blood pressure lowering medications (ACEi and beta blocker) was an interesting finding given that both medications are indicated for patients with hypertension and heart failure. It is widely known that ACS risk factors, including hypertension, heart failure and diabetes, are more prevalent in patients with low SES [26, 27], which was also found in the studies included in this review. Although ACEi and beta blocker are both similarly effective in controlling blood pressure [28], ACEi is recommended for patients with hypertension, diabetes and kidney disease, whereas, the use of beta blockers has been discouraged in patients with diabetes due to the masking of hypoglycaemic symptoms [29]. The increased prevalence of comorbidities in lower SES groups may be one of the reasons why ACEi was more often prescribed to the lowest than the highest SES group.

Three of the seven studies included in this review have explored the effect of a second socioeconomic measure, which also showed that patients with lower SES tended to receive prescriptions to recommended medication less often compared to those with higher SES. Gerber et al. reported a significant proportional difference in the percentage prescribed beta blockers between those with <12 years (32%) and ≥12 years (38%) of education [13]. However, the prescriptions of aspirin and ACEi were comparable (80% vs. 83% and 22% vs. 20%, respectively). After adjustment, Foraker et al. found that patients with Medicaid (predominantly those with low income) were less likely to receive aspirin (OR (95% CI): 0.92 (0.87, 0.98)) and composite medications (0.94 (0.88, 1.00)), although the prescription of composite medications were marginally significant with the upper CI on 1.00 [12]. The likelihood of being prescribed beta blocker and ACEi were not statistically significant. Kawecka-Jaszcz et al. explored the effect of employment on the prescription of lipid-lowering therapy, and found that the proportion of those who were prescribed lipid-lowering medication was lower by 8% for the unemployed than for the employed, however, the difference was not significant (39% vs. 47%; p > 0.05) [16]. Although the percent difference between the SES groups varied slightly between the socioeconomic measure used in the meta-analyses and the second socioeconomic measure, the results were comparable between different measures of SES. Regardless of the type of the SES, the rate of aspirin, beta blocker and lipid-lowering therapy prescriptions were lower for patients in the lowest SES group, whereas, the rate of ACEi prescription was higher for patients in the highest SES group.

ACS, being a disease with a high incidence of recurrent adverse clinical events, has recommended guidelines and clinical pathways in place to help clinicians provide optimal treatment to every patient. However, despite these inclusive recommendations, applicable to all patients, it is unclear as to why variation in the prescription of guideline-recommended medications between the SES groups is often found in studies. Reasons might include physicians’ clinical management that varies to accommodate patients’ financial status to lessen their burden, as was reported to have been done in primary care [30]. Further investigation would be needed to find factors that cause the discrepancy in the prescription of recommended medication at discharge to be able to find ways to provide equitable care for all patients and prevent a secondary event.

There were limitations to this review. First, the reviewed studies used observational data, which may be subject to reporting bias. Second, we could only compare between the lowest and the highest SES groups in the meta-analysis as some studies reported only two SES groups, therefore could not use complete data from all studies. Third, the studies being observational, comparison of likelihoods of the outcome after adjusting for covariates would have been ideal, however, due to the limited number of studies that aimed to find the effect of SES on the prescription of medications, studies with unadjusted data have also been included in the meta-analysis. Fourth, also because of the small number of studies found for this systematic review, the definitions and types of SES (deprivation score, income and education) and the level of SES (individual, neighbourhood and country) varied across the studies. Although subgroup analysis for the different types of SES could not be done, the results from the studies that reported the effect of two different types of SES on prescription of medications suggests that the different types of SES may not affect the study results greatly. Fifth, the studies included for this review may be limited due to our refined search terms. Sixth, the power to test for asymmetry and heterogeneity was substantially low with only 2–4 studies for each meta-analysis [31, 32].

Prescriptions of guideline-recommended secondary prevention medications at discharge varied according to the SES of patients. Patients from the lowest SES group were less often prescribed beta blocker and statin, but more often prescribed ACEi compared to those from the highest SES group. Adherence to guidelines and policies needs to be promoted to reduce the discrepancies between the lowest and the highest SES groups.