Abstract
Patients who have experienced an acute coronary syndrome (ACS) are at very high risk of recurrent atherosclerotic cardiovascular disease (CVD) events. Dyslipidaemia, a major risk factor for CVD, is poorly controlled post ACS in countries outside Western Europe and North America, despite the availability of effective lipid-modifying therapies (LMTs) and guidelines governing their use. Recent guideline updates recommend that low-density lipoprotein cholesterol (LDL-C), the primary target for dyslipidaemia therapy, be reduced by ≥ 50% and to < 1.4 mmol/L (55 mg/dL) in patients at very high risk of CVD, including those with ACS. The high prevalence of CVD risk factors in some regions outside Western Europe and North America confers a higher risk of CVD on patients in these countries. ACS onset is often earlier in these patients, and they may be more challenging to treat. Other barriers to effective dyslipidaemia control include low awareness of the value of intensive lipid lowering in patients with ACS, physician non-adherence to guideline recommendations, and lack of efficacy of currently used LMTs. Lack of appropriate pathways to guide follow-up of patients with ACS post discharge and poor access to intensive medications are important factors limiting dyslipidaemia therapy in many countries. Opportunities exist to improve attainment of LDL-C targets by the use of country-specific treatment algorithms to promote adherence to guideline recommendations, medical education and greater prioritisation by healthcare systems of dyslipidaemia management in very high risk patients.
Video Abstract
Similar content being viewed by others
Avoid common mistakes on your manuscript.
A systematic literature review of dyslipidaemia management after acute coronary syndrome (ACS) was conducted in patients outside Western Europe and North America |
Dyslipidaemia control post ACS is suboptimal |
Recent guidelines have lowered cholesterol targets for these patients |
High-intensity dyslipidaemia therapy is available but is prescribed infrequently |
Poor access to, and lack of reimbursement for, newer medications limits treatment |
Introduction
Dyslipidaemia is a major risk factor for atherosclerotic cardiovascular disease (CVD) and reducing low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-modifying therapy (LMT) [1, 2]. CVD may manifest clinically as an acute coronary syndrome (ACS), including myocardial infarction (MI) and unstable angina (UA). The very high risk of recurrent events post ACS makes control of CVD risk factors a priority in these patients. It is important to determine whether patients with ACS are receiving optimal treatment in clinical practice, and to consider opportunities for improving goal achievement. Guidelines recommend LMT to achieve specified LDL-C targets for secondary prevention [1, 2]. Large observational studies of patients with dyslipidaemia, conducted predominantly in Western Europe and North America, indicate that achievement of LDL-C targets is generally poor, particularly among patients at higher CVD risk [3,4,5,6]. Studies of lipid management in countries outside of these regions show similar results [7, 8]. This article will examine the current state of dyslipidaemia management in patients with ACS in regions outside Western Europe and North America. Strategies for improving LDL-C control in this patient group will be examined, and the potential impact of recent clinical trial data and changes to treatment guidelines will be discussed.
Key Guideline Recommendations
The American Heart Association (AHA)/American College of Cardiology (ACC) guidelines state ≥ 50% reduction in LDL-C as the primary goal of therapy post ACS, but recommend intensification of LMT if LDL-C remains ≥ 1.8 mmol/L (approx. 70 mg/dL) [9]. The American Association of Clinical Endocrinologist and American College of Endocrinology guidelines propose a target LDL-C of < 1.4 mmol/L (55 mg/dL) for patients at “extreme risk”, which include patients post ACS with additional risk factors such as early onset of CVD (age < 55 years in men; < 65 years in women), diabetes, chronic kidney disease (CKD) or heterozygous familial hypercholesterolaemia (HeFH) [10]. The target of < 1.4 mmol/L (55 mg/dL) is also recommended in guidelines in Taiwan for patients with ACS and diabetes [11]. Recently, the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) lowered their recommended LDL-C goal for all patients post ACS from < 1.8 mmol/L (70 mg/dL) to < 1.4 mmol/L (55 mg/dL) and an LDL-C reduction of ≥ 50%, and to < 1.0 mmol/L (< 40 mg/dL) for patients with CVD on maximally tolerated statins who experience a second vascular event within 2 years [2].
Most dyslipidaemia guidelines recommend high-intensity statin as first-line LMT post ACS; however, some local guidelines in Asia, e.g. China, recommend against the use of high-intensity statins, including post ACS and in patients with very high risk CVD [12]. Ezetimibe is recommended as second-line therapy when LDL-C goal is not achieved with maximal tolerated statin alone [1, 13], supported by the findings of the IMPROVE-IT trial [14]. Further intensification of LMT with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors is recommended post ACS in patients not at LDL-C goal with a statin–ezetimibe combination [1, 13]. The efficacy of PCSK9 inhibitors for reducing CVD events post ACS in patients treated with maximally tolerated statin therapy was established by the ODYSSEY OUTCOMES and FOURIER studies [15, 16].
Supporting Data
Systematic Literature Review
A systematic literature search of Embase and PubMed databases was conducted. The search aimed to identify observational studies and systemic literature reviews (SLRs) reporting lipid management data in patients with ACS in 28 countries outside Western Europe and North America (Electronic Supplementary Appendix for included countries). The publication date range was restricted to 1 January 2009 to 13 February 2019 for the standard databases, and to the 2 years prior to the search date (13 February 2019) for conference abstracts (via Embase). Further details of the methods and strings used are provided in the Electronic Supplementary Methods and Tables S1 and S3 in the Electronic Supplementary Material. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
A total of 2946 articles were identified (Fig. S1 in the Electronic Supplementary Material). After full-text screening, 68 articles met the pre-determined search criteria and were included in the final database. The included studies account for 17 countries of interest. Of the 68 studies, 61 were reported as journal articles and seven as meeting abstracts. No SLRs or meta-analyses were identified. The included studies were 32 prospective cohort studies, 15 retrospective cohort studies, 17 non-comparative studies, three cross-sectional studies, and one case–control study.
Online Panel Discussion
In June 2019, a panel consisting of seven renowned experts (cardiologists) from Colombia, Egypt, Israel, Mexico, South Africa, Taiwan and the United Arab Emirates was convened via an online discussion platform (Within3; https://www.within3.com). All panel members were authors on previous publications on dyslipidaemia in patients with ACS and were identified via a literature search. Potential panel members were invited on the basis of their willingness and availability to participate in the online discussion. All are co-authors of this paper. Informed by the findings of the SLR conducted in February 2019 and other supportive data, including local published studies and their personal experience, the panel considered the current state of dyslipidaemia management post ACS in regions outside Western Europe and North America. The panel discussion took place during three online sessions: 3 June to 2 July 2019, 15 August to 3 September 2019 and October 1 to 14 2019, facilitated by open-ended questions (Electronic Supplementary Appendix) relating to the findings of the SLR, and on current dyslipidaemia management practices, barriers to treatment and opportunities for improved lipid control in each expert’s country.
Limitations
The SLR included studies published in English only, and did not include those conducted in a wider patient population with dyslipidaemia that may have included patients with ACS. Consequently, the search may not have been fully representative of all studies reporting data for dyslipidaemia management in patients with ACS. The patient populations and healthcare systems in these countries are heterogenous, with substantial historical, cultural, economic, genetic, lifestyle and religious differences. This heterogeneity contributes to the variability of the data and limits cross-country comparisons; however, it reflects the variation in dyslipidaemia management in patients with ACS in the real-world setting. The countries represented by the panel was a subset only (seven countries) of those examined in studies identified by the SLR; therefore, the panel’s opinions and experience may not have fully reflected the state of dyslipidaemia management in all countries examined. Many of the studies identified by the SLR were performed before current guidelines were published and their findings may be based on previous recommendations for LMT and LDL-C targets. In particular, the ESC/EAS guidelines for dyslipidaemia management [2] were updated after the SLR was conducted.
Current State of Dyslipidaemia Management Post ACS in Countries Outside Western Europe and North America
Use of Guidelines
Information on the clinical guidelines followed, recommended LDL-C targets, LMTs commonly prescribed and details of the healthcare professional responsible for dyslipidaemia management post ACS was provided by members of the expert panel for their countries. These data were summarised and tabulated (Table 1).
The panel indicated that, in most countries represented, physicians follow recommendations of the ESC/EAS [13], AHA/ACC [9] and/or local consensus statements based on these recommendations. It should be noted that the panel discussion was initiated prior to publication of the 2019 update of the ESC/EAS guidelines [2]. In line with the AHA/ACC and previous ESC/EAS recommendations [13], an LDL-C target of < 1.8 mmol/L (70 mg/dL) was reported for most countries, although a lower target of < 1.3 mmol/L (50 mg/dL) had been adopted in Colombia [17], and the goal for patients post ACS with diabetes in Taiwan was < 1.4 mmol/L (55 mg/dL) [11]. The regional consensus statement on dyslipidaemia treatment in Mexico recommends a target of < 2.6 mmol/L (100 mg/dL); however, the panel member reported that following publication of the ODYSSEY-OUTCOMES study [15], current perception in Mexico is to treat to an LDL-C target of < 1.8 mmol/L (70 mg/dL) post ACS.
The panel noted that, in most countries, treatment algorithms based on the guidelines are employed to guide treatment decisions; the algorithm for Colombia has been published [17]. In some of the experts’ countries, long-term management post discharge for ACS was the responsibility of a specialist (e.g. cardiologist, endocrinologist, internist); however, follow-up for dyslipidaemia management was most often conducted by the general practitioner or primary care physician, who may be less familiar with the treatment algorithms and may prescribe lower than recommended doses of statin therapy.
Achievement of LDL-C Goals
Of studies included in the SLR, 25 reported data on LDL-C parameters post ACS and these are summarised in Table 2. LDL-C goal achievement rate was reported in 20 of these studies, and generally indicated suboptimal control of dyslipidaemia in this patient population. Rates of LDL-C goal achievement reported 1 month after ACS ranged from 56.1% to 83.5% (three studies). Studies reporting LDL-C goal achievement 1 year post ACS (five studies) reported rates of between 19.8% and 64.6%.
Use of LMT
Rates of statin use are provided for each study included in the SLR in Table S3 in the Electronic Supplementary Material and are summarised by country/region in Table 3. The majority of patients were treated with a statin after ACS. In most studies reporting statin use in hospital or at discharge, at least half of patients were taking statins (Table 3); 20/36 (56%) and 16/33 (48%) of studies reported rates of statin use of ≥ 90% in hospital and at discharge, respectively (Table S3 in the Electronic Supplementary Material). Of studies reporting statin use in hospital or at discharge, 11 reported rates of statin use at ≥ 1 subsequent time point; nine of these (82%) observed a reduction in rates of statin use over time (Table S3 in the Electronic Supplementary Material). Eight studies reported rate of statin use 1 year after ACS, with rates ranging from 59.4% to 87.0% (Table 3). A study of patients with ST-elevation MI (STEMI) in Turkey observed a lower mean LDL-C ± standard deviation in patients who continued taking statin medication after hospital discharge (2.69 ± 1.22 mmol/L, n = 79) compared with patients who discontinued statins (3.23 ± 0.99 mmol/L, n = 29) [18]. Studies reporting the rates of statin use according to type of ACS (STEMI, non-STEMI, UA) [19,20,21,22,23,24,25,26,27] generally reported similar rates for use in hospital and at discharge.
Use of High-Intensity LMT Statin Therapy
Few studies included in the SLR reported rates of high-intensity statin therapy post ACS; in those that did, rates varied widely between studies (Table 4). Low rates of ezetimibe use (≤ 11.3%) were reported (across six studies; Table 4), particularly after discharge from hospital.
Studies assessing LDL-C goal achievement demonstrate that, although patients on intensive LMT were more likely to achieve their LDL-C goal, target attainment rates were still suboptimal. For example, 57.3% of patients treated with high-potency statins in a study in Hong Kong (n = 2850) did not achieve LDL-C goal 12 months post ACS compared with 63.4% of patients treated with non-high-potency statins [28]. Consistent findings were noted in a study of 1026 patients with ACS in Turkey, in which patients treated with high-intensity statin therapy were more likely to achieve LDL-C targets compared with patients prescribed lower doses of statins; however, LDL-C goal achievement was still low (≤ 45.2%) [29]. A further study of 2034 Chinese patients with ACS receiving LMT but not at LDL-C goal reported that 71.5% of these patients were receiving intensive statin therapy [30]. A retrospective cohort study of 202 patients with ACS in China demonstrated that patients were more likely to achieve LDL-C goal if they were receiving ezetimibe plus statin (69.1%, P = 0.007) or intensive statin therapy (67.9%, P = 0.047) compared with moderate-intensity statin (46.9%) [31]. Consistent results were reported for a prospective cohort study in 84 Chinese patients with type 2 diabetes, which noted greater LDL-C goal achievement with statins plus ezetimibe (77%) compared with statins alone (45%) at 1 month post ACS [32].
Gaps in the Evidence
No studies included in the SLR reported rates of PCSK9 inhibitor use. Few studies examined patient subgroups that may be at increased risk of CVD compared with the post-ACS population as a whole. Two studies indicated that LDL-C goal achievement rates may be lower among patients with familial hypercholesterolaemia (FH). Auckle et al. [33] reported poorer LDL-C goal achievement (< 1.8 mmol/L or > 50% reduction) with moderate potency LMT at 1 year post STEMI in patients with possible FH compared with those without FH (18.7% vs. 51.4%) in China. In a separate study, patients (n = 3224) from the GULF COAST registry (2012–2013) were stratified by FH status (probable, possible or unlikely) [34]. Rates of statin use were similar in the three groups at discharge (96–98%) and at 1 year post ACS (93–96%); however, goal attainment rates differed between the groups (P < 0.001); 23% of patients in whom FH was unlikely achieved their LDL-C goal, compared with 13% and 12% of patients with probable and possible FH, respectively.
Impact of Recent Developments in Dyslipidaemia Management
Recent guidelines for the treatment of dyslipidaemia specify lower LDL-C targets for patients at very high risk of CVD than previous recommendations. Treating patients with ACS to an LDL-C target of < 1.4 mmol/L (55 mg/dL) is supported by the findings of the IMPROVE-IT [14], ODYSSEY-OUTCOMES [15] and FOURIER [16] studies. In IMPROVE-IT, addition of ezetimibe to high-dose simvastatin in patients with ACS lowered LDL-C to a mean of 1.4 mmol/L (53.2 mg/dL) and reduced CVD event rate compared with placebo without evidence of harm [14]. The benefit of ezetimibe on CVD event rate appeared to emerge after 1 year of treatment, was statistically significant at 7-year follow-up, and was particularly pronounced in elderly patients and in those with diabetes mellitus. The ODYSSEY-OUTCOMES trial is the only study to investigate the effects of a PCSK9 inhibitor in patients with ACS. It examined the effect of alirocumab in patients with ACS and LDL-C ≥ 1.8 mmol/L (70 mg/dL), non-high-density lipoprotein cholesterol ≥ 2.6 mmol/L (100 mg/dL) or apolipoprotein B ≥ 80 mg/dL despite statin therapy [15]. Addition of alirocumab lowered mean LDL-C to 1.24 mmol/L (48 mg/dL) at 12 months and reduced major CVD events and total mortality by 15% compared with placebo after a 2.8-year follow-up. FOURIER was conducted in statin-treated patients with stable coronary heart disease, peripheral artery disease or prior stroke and LDL-C ≥ 1.8 mmol/L (70 mg/dL) [16]. Patients treated with the PCSK9 inhibitor evolocumab had a mean LDL-C of 0.78 mmol/L (30 mg/dL) after 48 weeks of treatment. At follow-up (median 2.2 years), the risk of CVD events was reduced by 15% with evolocumab compared with placebo. On the basis of the findings of these studies, lowering the LDL-C goal for patients with ACS to < 1.4 mmol/L (55 mg/dL) would be expected to reduce the risk of recurrent events. Given the low attainment of higher LDL-C goals reported post ACS in the studies included in the SLR, these more stringent targets are unlikely to be met with current clinical practice, and greater use of intensive LMTs will be required.
The low rates of high-potency statin and ezetimibe use in the studies included in the SLR suggest that LMT is often not intensified in clinical practice. Despite recommendations of previous guidelines for LMT to achieve specified LDL-C targets, lipid testing and high-intensity statin use are often infrequent after ACS [35]. Current guidelines include clearer recommendations for the measurement of LDL-C during the course of ACS and for intensification of LMT [2, 9], which may encourage optimal dyslipidaemia management.
Lipoprotein(a) (Lp[a]) is an indicator of increased CVD risk and may identify patients at premature risk of ACS. The ESC/EAS guidelines recommend that measurement of Lp(a) should be considered at least once during an adult’s lifetime to identify those with very high inherited levels (> 180 mg/dL) [2]. These patients have a lifetime risk of CVD equivalent to that of patients with HeFH [36], and may therefore be candidates for aggressive LMT. An analysis of data from the FOURIER study demonstrated the potential benefit of PCSK9 inhibitors for reducing CVD risk in patients with elevated Lp(a) [37]. Evolocumab produced a significant reduction in Lp(a) levels (median 26.9% reduction at 48 weeks), and patients with higher baseline Lp(a) levels derived greater absolute CVD risk reductions from evolocumab treatment compared with those with lower baseline Lp(a).
Knowledge Gaps and Research Needs
Whether the LDL-C target for patients with ACS and other very high risk patients should be lowered further, e.g. < 1.3 mmol/L (50 mg/dL) is the subject of ongoing debate. The ESC/EAS guidelines state that an LDL-C goal of < 1.0 mmol/L (< 40 mg/dL) may be considered for patients with CVD who experience a second vascular event within 2 years while taking maximally tolerated statin-based therapy [2]. However, the panel reported that many physicians may be reluctant to treat to such low LDL-C levels because of long-term safety concerns, and further evidence of the safety of treating to very low LDL-C targets is needed.
Guidelines recommend the addition of ezetimibe in patients not at LDL-C goal with maximally tolerated statins, followed by further intensification with a PCSK9 inhibitor if needed to achieve LDL-C goal [2, 9]. The current recommendation of reserving treatment with PCSK9 inhibitors for patients not at LDL-C goals on a statin–ezetimibe combination is based on the wider availability and lower cost of ezetimibe, rather than on clinical evidence. The ODYSSEY-OUTCOMES and FOURIER trials allowed enrolment of patients treated with a statin–ezetimibe combination at baseline; however, most patients included were not treated with ezetimibe [15, 16]. These studies established the clinical efficacy of PCSK9 inhibitors in statin-treated patients; however, the efficacy of ezetimibe first followed by PCSK9 inhibitors for intensification of LMT post ACS has not been examined in randomised controlled trials, and further studies are needed. Newer LMTs, such as bempedoic acid and inclisiran, are currently in clinical development; however, their efficacy for reducing CVD risk has yet to be established in clinical trials [38].
The role of PCSK9 in the initial phase after ACS is poorly understood. Studies have shown a positive association between PCSK9 levels and severity of coronary artery lesions in patients with ACS [39,40,41], highlighting the potential importance of PCSK9 inhibitors immediately after ACS for neutralising these increased levels. The ESC/EAS guidelines state that PCSK9 inhibitors may be considered early upon admission for ACS in patients with LDL-C not at goal despite already taking a statin at the maximally tolerated dose [2]. The EVOPACS study (n = 308) examined the efficacy of evolocumab initiated on top of atorvastatin 40 mg during the in-hospital phase of ACS in patients with elevated LDL-C (≥ 1.8 mmol/L on high-intensity statin for at least 4 weeks; ≥ 2.3 mmol/L on low- or moderate-intensity statin; or ≥ 3.2 mmol/L on no stable dose of statin) [42]. Most patients (78.2%) were statin-naïve on admission. After 8 weeks, 95.7% of patients achieved an LDL-C goal of < 1.8 mmol/L with evolocumab compared with 37.6% with placebo. More data are required to confirm the findings that PCSK9 levels rise during the acute phase of ACS, to determine the influence of early high-dose statin use on PCSK9 levels during this period and to establish the clinical efficacy for reducing CVD risk of immediate treatment with PCSK9 inhibitors. The possibility of negative pleiotropic effects of early blockade of PCSK9 activity, and the long-term safety and efficacy of early initiation of PCSK9 inhibitors on top of statin–ezetimibe, needs to be established.
Several comorbidities increase CVD risk and may impact on dyslipidaemia management, including diabetes, peripheral artery disease, CKD, heart failure, non-alcoholic fatty liver disease, atrial fibrillation and premature CVD [1, 2]. Few data are available on dyslipidaemia management post ACS in patients with these conditions. In addition, more data are needed on the effects of other factors that may increase CVD risk or make the patient more challenging to treat, including age (elderly and young patients with premature atherosclerosis), menopausal status in women (i.e. pre vs. post menopause), chronic inflammatory disease, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and HIV infection. Given that genetic mutations that impact dyslipidaemia vary between ethnic groups, ethnicity is another important factor, and its effect on LDL-C goal achievement should be studied further. In addition to real-life observational studies in these subgroups, studies are also required to establish the efficacy of intensive LMT in these patient populations.
Barriers to Optimal Dyslipidaemia Management Post ACS
The findings of the SLR demonstrate that, although statins are widely prescribed after ACS, the intensity of therapy is suboptimal and the proportion of patients achieving target LDL-C levels is low. These findings suggest that dyslipidaemia management is often not conducted in line with guideline recommendations, especially in patients at high risk.
Not all patients with ACS are discharged from hospital on a statin. These patients may be less likely to receive subsequent statin therapy from their primary care physician or have their LDL-C level monitored regularly. Frequent monitoring of LDL-C, starting 6–8 weeks after discharge to assess response to therapy [2], is recommended, with intensification of LMT if not at goal [2, 9]. In many countries this may not be possible, and the panel report that monitoring of LDL-C is often not performed, either because physicians follow outdated guidelines, the ACS pathway for follow-up post discharge is not properly organised, follow-up is not arranged or the patient fails to attend. For patients who are followed up, a certain inertia regarding LDL-C control is quite prevalent among physicians intervening post discharge. They may either fail to set LDL-C goals or not monitor progress towards these goals. They may underestimate poor disease control and be uncertain about the need to intervene, accepting higher than recommended LDL-C targets [43, 44]. Primary care physicians may be reluctant to intensify treatment to comply with stringent LDL-C targets because of the perceived lower risk of CVD with time since ACS and the potential for adverse events with LMT. This may be particularly true for patients they perceive as being at higher risk of adverse events, such as the elderly and those with comorbidities in multiple concomitant medications. In addition, physicians often underestimate CVD risk [7], which may result in setting less aggressive LDL-C targets than those recommended for patients post ACS. The TRANSLATE-ACS study conducted in the USA reported that one-third of patients with MI discontinued at least one medication by 6 months post MI, although high rates of statin use (90% vs. 95% at discharge) were noted [45]. Of patients who discontinued statin therapy, 23.3% did so on the physician’s instruction (9.5% because the physician felt it was no longer needed). Advanced age and the presence of comorbidities were associated with reduced persistence with medications.
Poor patient compliance with long-term medication is also a likely factor in reducing the rate of LMT use over time. Poor patient understanding of the importance of dyslipidaemia as a CVD risk factor, lack of acknowledgement of disease severity and reluctance to have treatments intensified may contribute to non-compliance. In the TRANSLATE-ACS study, 26.0% of patients who discontinued statin therapy did so because of side effects, 9.5% did so because of cost and 6.4% did so for other patient-related reasons [45]. Private insurance and cost assistance were associated with higher persistence with medication.
A lack of effective pathways exists in patients with ACS post discharge. No active outreach to patients and no team approach to care post discharge for cardiovascular secondary prevention and LDL-C control are healthcare system factors that may contribute to undertreatment. The lack of a discharge letter with treatment-decision support for primary care physicians is another barrier to effective dyslipidaemia management in primary care. Limited availability and restrictive reimbursement practices are also key healthcare system barriers to intensification of LMT with newer medications. The findings of the SLR indicated a low rate of use of high-intensity statins and ezetimibe. PCSK9 inhibitors were not available in some countries at the time the studies were performed; however, the addition of PCSK9 inhibitors to statin therapy in patients not at goal with statins alone is predicted to improve LDL-C goal achievement rates and clinical outcomes [46]. Generic forms are not available for all LMTs and sometimes health insurance does not cover high-intensity statins or PCSK9 inhibitors.
The high prevalence of CVD risk factors [47,48,49] in certain countries outside Western Europe and North America contributes to premature atherosclerosis and an earlier onset of ACS and higher age-standardised mortality rates from ischaemic heart disease [50] in these regions. This includes the higher prevalence of FH in some regions as a result of founder effects (e.g. Afrikaners in South Africa) or traditional family marriages (e.g. Middle East) [51, 52]. Observational studies have demonstrated the early onset of ACS in these regions. For example, at 51.2 ± 10.3 years, the mean age for first presentation of acute MI in Middle Eastern countries is around 10 years younger than that reported in other regions of the world [49, 53]. The Egyptian CardioRisk project reported that premature ACS was common: of 1681 patients admitted to hospital with ACS, 43% of men were aged < 55 years, and 67% of women were aged < 65 years [47]. A study of South African Asian Indian patients with ACS reported mean ± standard deviation age at presentation as 54.6 ± 10.9 years [52]. Of patients presenting with ACS, 21.9% were aged ≤ 45 years and 54% had a family history of premature MI. Premature CVD comprises a subgroup of patients with ACS who are at extreme risk and deserve a more aggressive lipid-lowering strategy than those of other high-risk subgroups, but which may be challenging to treat.
Improving the Management of Dyslipidaemia After ACS in Countries Outside Western Europe and North America: Expert Panel Recommendations
The promotion of best practice in the management of dyslipidaemia post ACS requires several elements, including the development and use of county-specific consensus statements and treatment algorithms, medical and patient education, and changes in health practices.
LDL-C Goal Post ACS
The panel supports the recommendations of recent guideline updates that recommend lowering LDL-C to < 1.4 mmol/L (55 mg/dL) post ACS.
The ESC/EAS recommendations for FH screening are also supported as well as the use of Lp(a) to identify patients at higher risk of CVD, particularly for patients with premature atherosclerosis and those with a positive family history for CVD.
Combination LMT
All patients with ACS should receive a high-intensity statin therapy, unless contraindicated, regardless of the baseline LDL-C level. The IMPROVE-IT trial showed that in high-risk patients post ACS, ezetimibe 10 mg/simvastatin 40 mg was superior to simvastatin 40 mg alone in reducing long-term CVD events [14]. The 2019 ESC/EAS dyslipidaemia guidelines recommended follow-up of lipid profile within 4–6 weeks with the addition of a PCSK9 inhibitor if LDL-C goal is not achieved despite maximally tolerated statin dose and ezetimibe combination. It may also be reasonable to add a PCSK9 inhibitor during hospitalisation for patients admitted with ACS, who are not at LDL-C goal despite adherence to maximally tolerated LMT.
Use of Country-Specific Treatment Algorithms
Treatment algorithms are beneficial to guide treatment decisions and promote best practice. They define strategies to improve the management of dyslipidaemia and provide clear guidance on how (including dosage) and when patients should be initiated on statins, and when to intensify LMT with ezetimibe and PCSK9 inhibitors. A large study of patients with ACS in China (n = 29,346) supports their use, noting that initiation of a clinical pathway-based, multifaceted quality of care initiative in hospitals improved the use of appropriate therapies for secondary prevention at discharge [54]. Given the differences in healthcare systems and availability of newer LMTs between countries, and between hospitals within countries, treatment algorithms should be developed for the country in which they are to be used and should be tailored at a hospital level. These should be updated as newer therapies become available and guidelines are updated. An example of a country-specific clinical pathway for guiding the use of PCSK9 inhibitors is the one that has been developed for use in Colombia [17].
Improving Outpatient Follow-Up
Follow-up after discharge from hospital is vital to ensure monitoring of LDL-C levels and intensification of LMT for patients not at LDL-C goal. Initiating the appropriate secondary prevention management at discharge and providing a strategy or prescription for intensification of LMT when transferring the patient into primary care will result in a better outcome for the patient. Outpatient follow-up should be arranged prior to discharge, as this practice is associated with higher persistence with medication after ACS [45]. The patient’s lipid profile should be assessed 6–8 weeks post discharge and treatment intensified if LDL-C levels are not at target. Every effort should be made for all patients to be at target LDL-C goals within 6 months post index event. Lipid levels should be monitored at least annually in all patients to ensure that LDL-C levels remain at goal, which also indirectly enables clinicians to evaluate treatment compliance.
Medical Education
Medical education is important to raise awareness among physicians of the short- and long-term benefits of significant lipid lowering in the acute setting. The first medical contact should be trained to routinely measure LDL-C levels and initiate high-dose statin therapy or intensify current LMT with ezetimibe and PCSK9 inhibitors if appropriate. Physician education programmes and scientific symposia are encouraged for medical education, and the increasing use of online resources and social media to facilitate wider access to medical education is supported. Providing feedback to physicians on quality indices of dyslipidaemia management, e.g. annual reporting of statistics on uncontrolled dyslipidaemia from patient registries, is beneficial to encourage greater adherence to guideline recommendations.
Educating the patient in the importance of dyslipidaemia as a CVD risk factor and the benefit of LMT post ACS is a vital aspect of treatment. A study in Taiwan demonstrated that an electronic-based patient and family education system during hospitalisation resulted in higher prescription rates of guideline-recommended therapies including statins, and contributed significantly to adherence to these medications [55].
Prioritising Dyslipidaemia Management Within Healthcare Policy
It is essential that health policymakers recognise the importance of adequate dyslipidaemia management for reducing the risk of CVD in high risk patients. Effective LMTs are available, and reducing LDL-C to below recommended targets has proven clinical benefit for reducing major CVD events. Despite this, many patients remain at elevated risk because of undertreatment. With limited availability and reimbursement of newer medications, physician education is not enough to ensure patients are treated according to best practice recommendations. A global commitment is required to adopt effective LMT as a critical target of healthcare systems to improve prevention of CVD and reduce associated mortality and morbidity.
Conclusion
Recent guidelines have lowered their recommended LDL-C targets for patients with ACS. The new LDL-C goals are based on LDL-C levels achieved in clinical trials with intensive LMT that were associated with a reduced risk of CVD events. Studies reporting attainment of the previously recommended LDL-C goals in countries outside of Western Europe and North America have indicated that dyslipidaemia management is suboptimal in patients with ACS despite the availability of effective LMTs. Undertreatment is common, with few patients treated with high-intensity statins and/or ezetimibe. Greater intensification of LMT after ACS will be needed to achieve the more stringent targets now recommended.
While there is a need for improved medical education in the treatment of dyslipidaemia, a lack of availability and reimbursement of intensive LMTs is a key factor limiting dyslipidaemia management. CVD remains a leading cause of death worldwide, and effective LDL-C control improves clinical outcomes in patients with dyslipidaemia. The gap between guideline recommendations and clinical practice will not be addressed without greater prioritisation of adequate dyslipidaemia therapy by healthcare systems to enable wider access and greater use of intensive LMT.
Change history
09 May 2021
A peer-reviewed video abstract was retrospectively added to this publication
References
Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73:3168–209.
Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41:111–88.
Pearson TA, Laurora I, Chu H, Kafonek S. The lipid treatment assessment project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med. 2000;160:459–67.
Waters DD, Brotons C, Chiang CW, et al. Lipid treatment assessment project 2: a multinational survey to evaluate the proportion of patients achieving low-density lipoprotein cholesterol goals. Circulation. 2009;120:28–34.
Reiner Z, De Backer G, Fras Z, et al. Lipid lowering drug therapy in patients with coronary heart disease from 24 European countries—findings from the EUROASPIRE IV survey. Atherosclerosis. 2016;246:243–50.
Kotseva K, De Bacquer D, Jennings C, et al. Time trends in lifestyle, risk factor control, and use of evidence-based medications in patients with coronary heart disease in Europe: results from 3 EUROASPIRE surveys, 1999–2013. Glob Heart. 2017;12(315–22):e3.
Danchin N, Almahmeed W, Al-Rasadi K, et al. Achievement of low-density lipoprotein cholesterol goals in 18 countries outside Western Europe: the international cholesterol management practice study (ICLPS). Eur J Prev Cardiol. 2018;25:1087–94.
Gitt AK, Lautsch D, Ferrieres J, et al. Cholesterol target value attainment and lipid-lowering therapy in patients with stable or acute coronary heart disease: results from the dyslipidemia international study II. Atherosclerosis. 2017;266:158–66.
Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73:e285–350.
Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017;23:1–87.
Li YH, Ueng KC, Jeng JS, et al. 2017 Taiwan lipid guidelines for high risk patients. J Formos Med Assoc. 2017;116:217–48.
Hu DY. New guidelines and evidence for prevention and treatment of dyslipidemia and atherosclerotic cardiovascular disease in China. Chronic Dis Transl Med. 2017;3:73–4.
Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37:2999–3058.
Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387–97.
Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379:2097–107.
Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713–22.
Colombian Society of Cardiology. Clinical pathway for the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients over 13 years of age. 2017. http://www.scc.org.co/certificaciones/imagenes/Guia-clinica-21-noviembre-2017.pdf. Accessed 23 Aug 2019.
Yamaç AH, Kiliç U. Effect of statins on sirtuin 1 and endothelial nitric oxide synthase expression in young patients with a history of premature myocardial infarction. Turk Kardiyol Dern Ars. 2018;46:205–15.
Yusufali AM, AlMahmeed W, Tabatabai S, Rao K, Binbrek A. Acute coronary syndrome registry from four large centres in United Arab Emirates (UAE-ACS Registry). Heart Asia. 2010;2:118–21.
Iqbal F, Barkataki JC. Spectrum of acute coronary syndrome in North Eastern India—a study from a major center. Indian Heart J. 2016;68:128–31.
Singh A, Singh V, Ranjan R. Survey of assessment and management of coronary heart disease patients (SMART) in India. J Assoc Physicians India. 2017;65:22–6.
Wang R, Neuenschwander FC, Lima Filho A, et al. Use of evidence-based interventions in acute coronary syndrome—subanalysis of the ACCEPT registry. Arq Bras Cardiol. 2014;102:319–26.
Moustaghfir A, Haddak M, Mechmeche R. Management of acute coronary syndromes in Maghreb countries: the ACCESS (ACute Coronary Events—a multinational Survey of current management Strategies) registry. Arch Cardiovasc Dis. 2012;105:566–77.
Zubaid M, Rashed WA, Almahmeed W, et al. Management and outcomes of Middle Eastern patients admitted with acute coronary syndromes in the Gulf Registry of Acute Coronary Events (Gulf RACE). Acta Cardiol. 2009;64:439–46.
Chen KC, Yin WH, Wu CC, et al. In-hospital implementation of evidence-based medications is associated with improved survival in diabetic patients with acute coronary syndrome—data from TSOC ACS-DM Registry. Acta Cardiol Sin. 2018;34:211–23.
Shyu KG, Wu CJ, Mar GY, et al. Clinical characteristics, management and in-hospital outcomes of patients with acute coronary syndrome—observations from the Taiwan ACS full spectrum registry. Acta Cardiol Sin. 2011;27:135–44.
Alhabib KF, Hersi A, Alfaleh H, et al. Baseline characteristics, management practices, and in-hospital outcomes of patients with acute coronary syndromes: results of the Saudi project for assessment of coronary events (SPACE) registry. J Saudi Heart Assoc. 2011;23:233–9.
Yan BPY, Chan CKY, Tse G, et al. How to bridge residual distance to target LDL-C in acute coronary syndrome after initial statin therapy? Eur Heart J. 2017;38:P3681.
Guntekin U, Tosun V, Kilinc AY, et al. ST segment elevation myocardial infarction (STEMI) patients are more likely to achieve lipid-lowering treatment goals: a retrospective analysis of patients presenting with first acute coronary syndromes. Medicine. 2018;97:e12225.
Jiang J, Zhou YJ, Li JJ, et al. Uncontrolled hyperlipidemia in Chinese patients who experienced acute coronary syndrome: an observational study. Ther Clin Risk Manag. 2018;14:2255–64.
Dai YY, Zhang HS, Zhang XG, et al. Statin-ezetimibe versus statin lipid-lowering therapy in patients with acute coronary syndromes undergoing percutaneous coronary intervention. J Thorac Dis. 2017;9:1345–52.
Li L, Zhang M, Su F, et al. Combination therapy analysis of ezetimibe and statins in Chinese patients with acute coronary syndrome and type 2 diabetes. Lipids Health Dis. 2015;14:10.
Auckle R, Su B, Li H, et al. Familial hypercholesterolemia in Chinese patients with premature ST-segment-elevation myocardial infarction: prevalence, lipid management and 1-year follow-up. PLoS One. 2017;12:e0186815.
Al-Rasadi K, Al-Zakwani I, Alsheikh-Ali AA, et al. Prevalence, management, and outcomes of familial hypercholesterolemia in patients with acute coronary syndromes in the Arabian Gulf. J Clin Lipidol. 2018;12(685–92):e2.
Wang WT, Hellkamp A, Doll JA, et al. Lipid testing and statin dosing after acute myocardial infarction. J Am Heart Assoc. 2018;7:460. https://doi.org/10.1161/jaha.117.
Burgess S, Ference BA, Staley JR, et al. Association of LPA variants with risk of coronary disease and the implications for lipoprotein(a)-lowering therapies: a Mendelian randomization analysis. JAMA Cardiol. 2018;3:619–27.
O’Donoghue ML, Fazio S, Giugliano RP, et al. Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk. Circulation. 2019;139:1483–92.
Ray KK, Corral P, Morales E, Nicholls SJ. Pharmacological lipid-modification therapies for prevention of ischaemic heart disease: current and future options. Lancet. 2019;394:697–708.
Schmidt AF, Swerdlow DI, Holmes MV, et al. PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2017;5:97–105.
Bae KH, Kim SW, Choi YK, et al. Serum levels of PCSK9 are associated with coronary angiographic severity in patients with acute coronary syndrome. Diabetes Metab J. 2018;42:207–14.
Dalgic Y, Abaci O, Kocas C, et al. The relationship between protein convertase subtilisin kexin type-9 levels and extent of coronary artery disease in patients with non-ST-elevation myocardial infarction. Coron Artery Dis. 2020;31:81–6.
Koskinas KC, Windecker S, Pedrazzini G, et al. Evolocumab for early reduction of LDL-cholesterol levels in patients with acute coronary syndromes (EVOPACS). J Am Coll Cardiol. 2019;74:2452–62.
Blom DJ, Almahmeed W, Al-Rasadi K, et al. Low-density lipoprotein cholesterol goal achievement in patients with familial hyphercholesterolemia in countries outside Western Europe: the international cholesterol managament practice study. J Clin Lipidol. 2019;13:594–600.
Pijlman AH, Huijgen R, Verhagen SN, et al. Evaluation of cholesterol lowering treatment of patients with familial hypercholesterolemia: a large cross-sectional study in the Netherlands. Atherosclerosis. 2010;209:189–94.
Mathews R, Wang TY, Honeycutt E, et al. Persistance with secondary prevention medications after acute myocardial infarction: insights from the TRANSLATE-ACS study. Am Heart J. 2015;170:62–9.
Yan BP, Chan CK, Tse G, et al. Projected efficacy of statin mono- and combination therapy based on distance from baseline to target LDL-C level in acute coronary syndrome. Value Health. 2018;21:S26.
Reda A, Ashraf M, Soliman M, et al. The pattern of risk-factor profile in Egyptian patients with acute coronary syndrome: phase II of the Egyptian cross-sectional cardiorisk project. Cardiovasc J Afr. 2019;30:87–94.
Juarez-Herrera U, Jerjes-Sanchez C, Renasica II Investigators. Risk factors, therapeutic approaches, and in-hospital outcomes in Mexicans with ST-elevation acute myocardial infarction: the RENASICA II multicenter registry. Clin Cardiol. 2013;36:241–8.
Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937–52.
Roth GA, Johnson C, Abajobir A, et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J Am Coll Cardiol. 2017;70:1–25.
EAS Familial Hypercholesterolaemia Studies Collaboration, Vallejo-Vaz AJ, De Marco M, et al. Overview of the current status of familial hypercholesterolaemia care in over 60 countries—the EAS familial hypercholesterolaemia studies collaboration (FHSC). Atherosclerosis. 2018;277:234–55.
Ranjith N, Pegoraro RJ, Zaah MG. Risk factors associated with acute coronary syndromes in South African Adian Indian patients (the AIR study). J Clin Exp Cardiol. 2011;2:1000163.
Gehani AA, Al-Hinai AT, Zubaid M, et al. Association of risk factors with acute myocardial infarction in Middle Eastern countries: the INTERHEART Middle East study. Eur J Prev Cardiol. 2014;21:400–10.
Wu Y, Li S, Patel A, et al. Effect of a quality of care improvement initiative in patients with acute coronary syndrome in resource-constrained hospitals in China: a randomized clinical trial. JAMA Cardiol. 2019;4:418–27.
Lee CK, Lai CL, Lee MH, et al. Reinforcement of patient education improved physicians’ adherence to guideline-recommended medical therapy after acute coronary syndrome. PLoS One. 2019;14:e0217444.
Al-Sayed N, Al-Waili K, Alawadi F, et al. Consensus clinical recommendations for the management of plasma lipid disorders in the Middle East. Int J Cardiol. 2016;225:268–83.
Alshamiri M, Ghanaim MMA, Barter P, et al. Expert opinion on the applicability of dyslipidemia guidelines in Asia and the Middle East. Int J Gen Med. 2018;11:313–22.
The Egyptian Cardiology Task Force Board members. The Egyptian consensus of dyslipidaemia management. 2017. http://www.mohealth.gov.eg/UserFiles/LibraryFiles/295396.pdf. Accessed 10 Dec 2019.
Klug E, Raal FJ, Marais AD, et al. South African dyslipidaemia guideline consensus statement: 2018 update. A joint statement from the South African Heart Association (SA Heart) and the Lipid and Atherosclerosis Society of Southern Africa (LASSA). S Afr Med J. 2018;108:973–1000.
Lopez MJ, Morales PK, Fontes LRD, et al. Guía de tratamiento farmacológico de dislipidemias para el primer nivel de atención. Rev Mex Cardiol. 2013;24:103–29.
Carvalho LS, Martins NV, Moura FA, et al. High-density lipoprotein levels are strongly associated with the recovery rate of insulin sensitivity during the acute phase of myocardial infarction: a study by euglycemic hyperinsulinemic clamp. J Clin Lipidol. 2013;7:24–8.
Atkins ER, Du X, Wu Y, et al. Use of cardiovascular prevention treatments after acute coronary syndrome in China and associated factors. Int J Cardiol. 2017;241:444–9.
Sobhy M, El Etriby A, El Nashar A, et al. Prevalence of lipid abnormalities and cholesterol target value attainment in Egyptian patients presenting with an acute coronary syndrome. Egypt Heart J. 2018;70:129–34.
Gitt AK, Lautsch D, Ferrières J, et al. Contemporary data on treatment practices for low-density lipoprotein cholesterol in 3867 patients who had suffered an acute coronary syndrome across the world. Data Brief. 2017;16:369–75.
Lee VW, Chau RY, Cheung HY, et al. How low should we target the LDL goal to improve survival for acute coronary syndrome patients in Hong Kong? BMC Cardiovasc Disord. 2015;15:117.
Yan BPY, Chan CKY, Tse G, et al. A paradox of under-treatment of acute coronary syndrome patients with low baseline LDL-C < 1.8 mmol/L. Eur Heart J. 2017;38:P3679.
Lee VW, Wang Y, Wu J, et al. The impact of low-density lipoprotein cholesterol goal attainments on cardiovascular outcomes: a retrospective cohort study in chinese acute coronary syndrome patients. Value Health. 2017;20:A262.
Yan BP, Chiang FT, Ambegaonkar B, et al. Low-density lipoprotein cholesterol target achievement in patients surviving an acute coronary syndrome in Hong Kong and Taiwan—findings from the dyslipidemia international study II. Int J Cardiol. 2018;265:1–5.
Jaywant SV, Singh AK, Prabhu MS, Ranjan R. Statin therapy/lipid lowering therapy among Indian adults with first acute coronary event: the dyslipidemia residual and mixed abnormalities IN spite of statin therapy (REMAINS) study. Indian Heart J. 2016;68:646–54.
Patel JP, Parikh KH, Patel JC, et al. Diabetes and management of lipid level following PCI in acute coronary syndrome patients. Int J Pharm Res. 2010;2:13–20.
Klempfner R, Goldenberg I, Fisman EZ, et al. Comparison of statin alone versus bezafibrate and statin combination in patients with diabetes mellitus and acute coronary syndrome. Am J Cardiol. 2014;113:12–6.
Ozaydın M, Türker Y, Erdoğan D, et al. Effect of previous statin use on the incidence of sustained ventricular tachycardia and ventricular fibrillation in patients presenting with acute coronary syndrome. Anadolu Kardiyol Derg. 2011;11:22–8.
de Matos Soeiro A, de Barros ESPG, Roque EA, et al. Mortality reduction with use of oral beta-blockers in patients with acute coronary syndrome. Clinics (Sao Paulo). 2016;71:635–8.
Filgueiras Filho NM, Feitosa Filho GS, Solla DJF, et al. Implementation of a regional network for ST-segment-elevation myocardial infarction (STEMI) care and 30-day mortality in a low- to middle-income city in Brazil: findings from Salvador’s STEMI Registry (RESISST). J Am Heart Assoc. 2018;7:14.
Gaedke M, Costa JS, Manenti ER, et al. Use of medicines recommended for secondary prevention of acute coronary syndrome. Rev Saude Publica. 2015. https://doi.org/10.1590/s0034-8910.2015049005978.
Maier Gde S, Martins EA. Health care for patients with acute coronary syndrome according to quality indicators. Rev Bras Enferm. 2016;69:757–64.
Nicolau JC, Franken M, Lotufo PA, et al. Use of demonstrably effective therapies in the treatment of acute coronary syndromes: comparison between different Brazilian regions. Analysis of the Brazilian Registry on Acute Coronary Syndromes (BRACE). Arq Bras Cardiol. 2012;98:282–9.
Piegas LS, Avezum A, Guimaraes HP, et al. Acute coronary syndrome behavior: results of a Brazilian registry. Arq Bras Cardiol. 2013;100:502–10.
Santos ES, Baltar VT, Pereira MP, et al. Comparison between cardiac troponin I and CK-MB mass in acute coronary syndrome without ST elevation. Arq Bras Cardiol. 2011;96:179–87.
Soeiro AM, Araújo VA, Vella JP, et al. Is there any relationship between TSH levels and prognosis in acute coronary syndrome? Arq Bras Cardiol. 2018;110:113–8.
Todo MC, Bergamasco CM, Azevedo PS, et al. Impact of coronary intensive care unit in treatment of myocardial infarction. Rev Assoc Med Bras. 1992;2017(63):242–7.
Nazzal C, Frenz P, Alonso FT, Lanas F. Effective universal health coverage and improved 1-year survival after acute myocardial infarction: the Chilean experience. Health Policy Plan. 2016;31:700–5.
Bi Y, Gao R, Patel A, et al. Evidence-based medication use among Chinese patients with acute coronary syndromes at the time of hospital discharge and 1 year after hospitalization: results from the Clinical Pathways for Acute Coronary Syndromes in China (CPACS) study. Am Heart J. 2009;157:509–16.
Hao Y, Liu J, Liu J, et al. Sex differences in in-hospital management and outcomes of patients with acute coronary syndrome. Circulation. 2019;139:1776–85.
Li M, Huang Y, Du X, et al. Impact of prior use of four preventive medications on outcomes in patients hospitalized for acute coronary syndrome—results from CPACS-2 Study. PLoS One. 2016;11:e0163068.
Sun YJ, Li YZ, Jiang DM, et al. Relationship between low-density lipoprotein levels on admission and 1-year outcome in patients with acute ST-segment-elevation myocardial infarction. Kaohsiung J Med Sci. 2013;29:206–13.
Tian L, Yang Y, Zhu J, et al. Impact of previous stroke on short-term myocardial reinfarction in patients with acute ST segment elevation myocardial infarction: an observational multicenter study. Medicine. 2016;95:e2742.
Wang Y, Cong H, Lu C, Liu J, Wu J. Use of secondary prevention medications among patients with acute coronary syndromes in Tianjin, China. Value Health. 2017;20:A276–7.
Poh KK, Ambegaonkar B, Baxter CA, et al. Low-density lipoprotein cholesterol target attainment in patients with stable or acute coronary heart disease in the Asia-Pacific region: results from the Dyslipidemia International Study II. Eur J Prev Cardiol. 2018;25:1950–63.
Siddiqui A, Toaima K, Fakher M, Hamed L, Siddiqui T. Assessment of hospital performance using quality of care indicators in patients with acute ST elevation myocardial infarction (AQcare-STEMI). Eur Heart J Acute Cardiovasc Care. 2018;7:226.
Al-Rasadi K, Al-Zakwani I, Zubaid M, et al. Prevalence, predictors, and impact of low high-density lipoprotein cholesterol on in-hospital outcomes among acute coronary syndrome patients in the Middle East. Open Cardiovasc Med J. 2011;5:203–9.
Al-Jarallah M, Al-Mallah MH, Zubaid M, et al. Trends in the use of evidence-based therapies early in the course of acute myocardial infarction and its influence on short term patient outcomes. Open Cardiovasc Med J. 2011;5:171–8.
Al Saleh AS, Alhabib KF, Alsheik-Ali AA, et al. Predictors and impact of in-hospital recurrent myocardial infarction in patients with acute coronary syndrome: findings from Gulf RACE-2. Angiology. 2017;68:508–12.
Shehab A, Al-Dabbagh B, AlHabib KF, et al. Gender disparities in the presentation, management and outcomes of acute coronary syndrome patients: data from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2). PLoS One. 2013;8:e55508.
El-Hajj MS, Saad A, Al-Suwaidi J. Utilization of evidence-based secondary prevention medications at the time of discharge in patients with acute coronary syndrome (ACS) in Qatar. Curr Vasc Pharmacol. 2016;14:394–403.
Naeem KB, Abdulrazzaq N. Demographics of acute myocardial infarction: experience at a non-PCI (percutaneous coronary intervention) center in Middle East. Eur Heart J Acute Cardiovasc Care. 2018;7:241.
Al-Zakwani I, Zubaid M, Alsheikh-Ali AA, Almahmeed W, Rashed W. Effect of evidence-based cardiac drug therapy on mortality in patients with acute coronary syndrome: findings from the Gulf COAST registry. Cardiovasc Ther. 2018;36:e12463.
Banerjee S, Kumar V, Ramachandran P, Kamath A. Does the pharmacological management of unstable angina vary with age and gender—a descriptive study. J Clin Diagn Res. 2010;4:3150–7.
Dilip C, Cholamugath S, Baby M, Pattani D. Prevalence of cardiovascular risk factors and management practices of acute coronary syndrome in a tertiary care hospital. J Basic Clin Physiol Pharmacol. 2015;26:547–54.
Mohanan PP, Mathew R, Harikrishnan S, et al. Presentation, management, and outcomes of 25,748 acute coronary syndrome admissions in Kerala, India: results from the Kerala ACS Registry. Eur Heart J. 2013;34:121–9.
Pagidipati NJ, Huffman MD, Jeemon P, et al. Association between gender, process of care measures, and outcomes in ACS in India: results from the detection and management of coronary heart disease (DEMAT) registry. PLoS One. 2013;8:e62061.
Sharma KK, Mathur M, Lodha S, et al. Study of differences in presentation, risk factors and management in diabetic and nondiabetic patients with acute coronary syndrome. Indian J Endocrinol Metab. 2016;20:354–8.
Hammer Y, Iakobishvili Z, Hasdai D, et al. Guideline-recommended therapies and clinical outcomes according to the risk for recurrent cardiovascular events after an acute coronary syndrome. J Am Heart Assoc. 2018;7:e009885.
Kopel E, Klempfner R, Goldenberg I, Schwammenthal E. Estimating mortality in survivors of the acute coronary syndrome by the 4-drug score. Cardiology. 2014;127:83–9.
Erlikh AD. Evolution of acute coronary syndrome treatment during last years in Russian hospitals (based on results of RECORDS registries). Circulation. 2017;10:A162.
Griffiths B, Lesosky M, Ntsekhe M. Self-reported use of evidence-based medicine and smoking cessation 6–9 months after acute coronary syndrome: a single-centre perspective. S Afr Med J. 2014;104:483–7.
Lee CH, Fang CC, Tsai LM, et al. Patterns of acute myocardial infarction in Taiwan from 2009 to 2015. Am J Cardiol. 2018;122:1996–2004.
Cheng CC, Huang WC, Chiou KR. Body mass index and outcome of acute myocardial infarction—is there an obesity paradox? Acta Cardiol Sin. 2013;29:413–20.
Nguyen T, Le KK, Cao HTK, et al. Association between in-hospital guideline adherence and postdischarge major adverse outcomes of patients with acute coronary syndrome in Vietnam: a prospective cohort study. BMJ Open. 2017;7:e017008.
Nguyen T, Nguyen TH, Pham HT, et al. Physicians’ adherence to acute coronary syndrome prescribing guidelines in Vietnamese hospital practice: a cross-sectional study. Trop Med Int Health. 2015;20:627–37.
Acknowledgements
Funding
This research was funded by Sanofi. Sanofi were involved in the design of the research and were allowed to review drafts during manuscript development. The design and implementation of the SLR, together with initial analysis of outputs from the SLR, was performed by Doctor Evidence (Santa Monica, CA, USA) with funding from Sanofi and under the direction of the authors. The authors were responsible for further analysis and interpretation of data derived from the SLR. The online panel discussions between the authors were facilitated using the Within3 platform (https://www.within3.com), with access to this platform funded by Sanofi. Ultimate responsibility for opinions, conclusions and data interpretation lies with the authors. Sanofi funded the journal’s rapid service and open access fees.
Authorship
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Medical Writing Assistance
The authors thank Veronique Daclin, MD, from Sanofi for her contribution and Gemma Grundy, BSc, from Sanofi for coordinating the development of this manuscript. Medical writing assistance and editorial support, under the direction of the authors, were provided by Fiona Van, PhD, and Elke Sims, MLangTrans, both of Prime (Knutsford, UK), funded by Sanofi according to Good Publication Practice guidelines (https://annals.org/aim/fullarticle/2424869/good-publication-practicecommunicating-company-sponsored-medical-research-gpp3).
Authorship Contributions
TS contributed to the design of the SLR and the acquisition of the data. AR, WA, ID-M, PH, UJ-H, NR and MU-T contributed to the interpretation of the data and provided their expert opinion during the online discussion forum. All authors critically reviewed the manuscript and approved the manuscript for submission. All authors meet the criteria for authorship.
Disclosures
Ashraf Reda, Wael Almahmeed, Idit Dobrecky-Mery, Po-Hsun Huang, Ursulo Juarez-Herrera, Naresh Ranjith, Tobias Sayre and Miguel Urina-Triana have nothing to disclose.
Compliance with Ethics Guidelines
This review is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Author information
Authors and Affiliations
Corresponding author
Additional information
Digital Features
To view digital features for this article go to https://doi.org/10.6084/m9.figshare.11973354.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
About this article
Cite this article
Reda, A., Almahmeed, W., Dobrecky-Mery, I. et al. A Narrative Review and Expert Panel Recommendations on Dyslipidaemia Management After Acute Coronary Syndrome in Countries Outside Western Europe and North America. Adv Ther 37, 1754–1777 (2020). https://doi.org/10.1007/s12325-020-01302-4
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12325-020-01302-4