37 Prevalence of secondary prevention medication use in South America 2 cardioprotective medications have a low cost (like aspirin), and in Argentina, Chile and Brazil, four of the medication classes (antiplatelets, beta-blockers ACEI , and statins) studied in this review are available free of charge (12,73,79). Some studies remark that although medications may be affordable, not all of them are always available in the public sector (48,76,77,81). The higher medication use in the higher SES patients may be explained by affordability and access to private healthcare (8,48,77,81). Health care setting Our meta-regression showed that health care setting was independently associated with the use of beta-blockers, antiplatelet drugs, aspirin and statin. In particular, in comparison to tertiary centers, the use of these medications was lower in primary care and community settings; use of antiplatelet drugs was lower in public centres; and use of aspirin was lower in cardiac rehabilitation settings. These findings are in line with previous results showing medication prevalence to be lower in studies conducted in primary care settings compared to those conducted in tertiary hospitals (8,59,81). This may in part be due to overestimation of medication utilization prevalence in tertiary level clinical settings. First, patients attending tertiary centres may be older or more severely ill. Academic and tertiary hospitals have more capacity to provide active follow-up to patients compared to centres where care may be more fragmented. Therefore, patients attending academic or tertiary level centres for follow-up after an event may receive more specialized advice and prescriptions than patients attending a primary care facility, resulting higher rates of medication use.(59,81). Furthermore, it has been suggested that studies conducted in tertiary care settings may not include individuals without access to care (4). Therefore, it is important to consider the setting of the study when interpreting results from research on prevalence of medication use. Strengths This review summarizes evidence of a large number of studies from South America published in English, Spanish and Portuguese between 2000 and 2021. The comprehensive search included any article that contained data on any of the cardioprotective medication assessed in secondary prevention of CHD: anti-platelet drugs, lipid-lowering drugs, antihypertensive agents (beta-blockers, ACE-inhibitors, ARBs, diuretics, and nitrates), oral hypoglycaemics and insulin. We included articles from regional and international databases, and from a variety of settings (public and private centres, academic/ tertiary centres and community settings, and urban and rural areas). In light of the results of this review, which shows that care setting may influence the estimation of medication use prevalence, it is especially valuable that our review includes studies conducted in various settings. In total, this review pooled the prevalence of use of cardioprotective medication of 23938 participants. Most of the articles included in this review had a low or moderate risk of bias, indicating low risk of bias for the pooled estimate. Limitations
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