From guidelines to practice: LDL-C achievement in very high cardiovascular risk patients – analysis of the EDHIPO MARCA registry

Abstract

Background

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Cardiovascular disease remains the leading cause of morbidity and mortality worldwide, with dyslipidemia playing a key role in its progression. Despite advances in lipid-lowering therapy (LLT), LDL-C (Low-Density Lipoprotein Cholesterol) goal achievement remains suboptimal. This study evaluated LDL-C goal attainment in Colombian patients with very high cardiovascular risk (CVR) due to coronary artery disease (CAD) following ESC/EAS guidelines updates.

Methods

EDHIPO MARCA (Evaluación De adherencia a la terapia HIPOlipemiante en pacientes de Muy Alto Riesgo CArdiovascular) is a retrospective, multicenter study assessing LDL-C goal achievement in patients with CAD. Data were collected from previous coronary angiogram reports and medical records across 11 Colombian healthcare institutions with certified interventional cardiology services. Patients with CAD who had at least one follow-up LDL-C measurement and an LLT prescription within 12 months post-angiogram were included. LDL-C goal attainment was assessed across three periods—2011–2012, 2016–2017, and 2021–2022—corresponding to the updates of ESC/EAS guidelines (2011, 2016, and 2019, respectively). The LDL-C goals were <70 mg/dL for the first two periods and <55 mg/dL for the most recent one. LDL-C was measured or estimated using the Friedewald equation. Descriptive analyses were performed.

Results

A total of 1,788 patients were included, with a median age of 66 years (IQR: 59–74), and 70.7% were male. Hypertension (67.5%) and overweight (40.8%) were the most common comorbidities. At discharge, statins were prescribed in 84.1% (95% CI: 82.4–85.8%) of patients, increasing to 99.1% (95% CI: 98.6–99.5%) at the end of follow-up (median 6.8 months); PCSK9 inhibitors were prescribed in 1.5%, exclusively in 2019. At the end of follow-up, 36.6% (95% CI: 34.3%, 38.8%) achieved LDL-C goals. By guideline period, goal attainment was 12.1% (95% CI: 5.4%, 18.8%) in 2011, 42.3% (95% CI: 37.9%, 46.8%) in 2016, and 36.2% (95% CI: 33.5%, 38.9%) in 2019. By number of follow-ups, LDL-C goal achievement increased from 32.9% (1 follow-up) to 44.0% (4 follow-ups).

Conclusions

Despite widespread LLT use, LDL-C target achievement remains suboptimal. Frequent follow-up and greater use of combination therapy beyond statins may be essential to improve lipid control in very high CVR patients.

Background

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, posing a major global health challenge [1]. Between 1990 and 2019, the number of CVD cases nearly doubled, rising from 272 million to 523 million, alongside an increase in deaths from 12.1 million to 18.6 million during the same period [2]. In 2013, in the United States (US) one person died from CVD every 40 s, while in Europe, atherosclerotic cardiovascular disease (ASCVD) caused over 4 million deaths annually [3, 4]. Coronary artery disease (CAD), a key contributor to CVD, affected 154 million people globally in 2016, accounting for 32.7% of the CVD burden and 2.2% of the total disease burden. Despite medical advances, CAD remains a leading cause of death and a major healthcare challenge [5]. In Latin America, CAD is responsible for 35% of all deaths [6].

Beyond its high mortality rate, Disability-Adjusted Life Years (DALYs) linked to CVD rose from 279.8 million to 393.1 million over the same period [7]. The economic burden of CVDs is also substantial; for instance, the US incurred total costs of $555 billion by 2015, with projections reaching $1.1 trillion by 2035. In low- and middle-income countries, CVD-related costs totaled $3.7 trillion between 2011 and 2015 [1, 8]. Specifically, CAD contributes 185 million DALYs and imposes a significant financial strain, with annual patient costs often exceeding per capita health expenditures. Pooled direct costs range from 4.9 to 137.8% of gross domestic product per capita, averaging 21.7%, underscoring both the economic burden and regional disparities [9].

Among modifiable risk factors for CVD, dyslipidemia is one of the most significant. Hypercholesterolemia, particularly elevated levels of low-density lipoprotein cholesterol (LDL-C), is highly prevalent and is a primary contributor to ASCVD [10]. LDL-C triggers atherosclerosis via arterial lipoprotein retention. Subsequently, Ox-LDL aggravates the process through endothelial dysfunction and plaque destabilization, heightening thrombotic risk [11, 12]. This condition is widespread, for instance, World Health Organization estimates from 2020 indicate that hypercholesterolemia presented a prevalence of 54% in Europe and 48% in the Americas [13]. Elevated LDL-C is particularly concerning in patients with prior cardiovascular events due to their higher risk of recurrence, morbidity, and mortality [14].

Lipid-lowering therapies (LLT) are essential for controlling LDL-C levels and preventing CVDs. Statins remain the cornerstone of LLT; however, newer pharmacological classes, such as proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), have also shown significant success in reducing cardiovascular events [15]. Despite the evidence supporting these therapies and their effectiveness in reducing CVDs, target achievement rates range between 31.1% and 54.0% [16,17,18]. Consistent with global findings, the achievement rate of LDL-C goals among Colombian patients ranges between 43.5% and 56% [19,20,21,22]. Notably, the PURE study, which enrolled 153,996 patients from 17 countries, demonstrated a low use of medications for secondary prevention in CAD, including statins (16.7%), with especially low rates in middle- and low-income countries (26% and 4.5%, respectively) [23].

LDL-C goals have become increasingly stringent with successive updates to the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines. Between 2011 and 2019, the target LDL-C level for very high cardiovascular risk (CVR) patients was lowered from below 70 mg/dL to below 55 mg/dL to optimize health outcomes in this population [3, 24, 25]. Despite these recommendations, recent studies report that only about 20% of patients achieve the LDL-C goal established in the 2019 guideline [26].

Accordingly, evaluating patients at very high CVR in Colombia remains essential to better understand their clinical characteristics and lipid control dynamics. The EDHIPO MARCA (Evaluación De adherencia a la terapia HIPOlipemiante en pacientes de Muy Alto Riesgo CArdiovascular) Registry is a national initiative that evaluates the achievement of LDL-C goals in patients classified as very high CVR due to the presence of CAD [27] undergoing LLT, according to the ESC/EAS guidelines published in 2011, 2016, and 2019, across various healthcare institutions nationwide. Therefore, our study provides valuable insights into lipid management practices at both national and Latin American regional levels (Fig. 1).

Fig. 1

Central figure

Methods and material

Study design

The EDHIPO MARCA Registry is a retrospective, descriptive, and multicenter study designed to evaluate LDL-C goal achievement and the use of LLT in patients at very high CVR due to established CAD. As defined by the 2019 ESC/EAS guidelines, very high CVR includes individuals with documented ASCVD, either clinical or unequivocal on imaging [3]. Accordingly, patients were included based on two criteria: those with angiographic evidence of multivessel coronary disease involving >50% stenosis in two major epicardial arteries fulfilled the imaging definition of ASCVD. In patients with <50% stenosis, inclusion required a clinical indication for coronary angiogram such as non-ST-elevation myocardial infarction (NSTEMI), ST-elevation myocardial infarction (STEMI), unstable angina or stable angina, which are explicitly included in the ESC/EAS definition of very high CVR.

The study reviewed coronary angiogram reports and medical records from multiple high-complexity reference institutions in Colombia. LDL-C goal attainment was assessed across three specific periods—2011–2012, 2016–2017, and 2021–2022—corresponding to the updates of ESC/EAS guidelines (2011, 2016, and 2019, respectively). The study aimed to assess each guideline update along with the following year; however, for the 2019 guideline, the subsequent year was 2020, when the COVID-19 pandemic hindered outpatient follow-up in this population. Therefore, we included the period 2021–2022 instead. Patients were included if they had clinically or imaging-confirmed CAD. Medical follow-up records reporting LDL-C levels for up to one-year after coronary angiogram were assessed. Patients with at least one follow-up record were included, with a maximum of four follow-up assessments per patient. Follow-up windows after coronary angiogram were categorized into 3-month intervals for analysis: 1 day to 3 months, 3 months and 1 day to 6 months, 6 months and 1 day to 9 months, and 9 months and 1 day to 12 months.

Study population and setting

The study population included adult patients who attended healthcare institutions with certified interventional cardiology services participating in the EDHIPO MARCA Registry, conducted in various cities and regions throughout Colombia. The registry was coordinated by the Centro de Investigaciones Clínicas of Fundación Valle del Lili. Eligible patients met the following criteria:

• a. Documented CAD, confirmed either clinically or by coronary angiogram performed in 2011, 2012, 2016, 2017, 2021, or 2022, for any indication;

• b. At least one reported lipid panel, including LDL-C, within 12 months following angiogram; and

• c. Documented prescription of LLT at follow up.

LDL-C was measured directly or estimated using the Friedewald Eq. [28]. When both values were available, the direct measurement was prioritized. If the same patient underwent two coronary angiograms in a single year, only the first was considered. Exclusion criteria included patients requiring dialysis for chronic kidney disease or with uncontrolled hypothyroidism at the time of angiogram, both due to their potential impact on lipid metabolism.

Data collection

Data were retrospectively extracted from medical records at each participating institution, covering sociodemographic characteristics, medical history, coronary angiogram results, lipid profile and LLT. Data collection was conducted using case report forms (CRFs) digitized in the Research Electronic Data Capture (REDCap) system, ensuring participant anonymity and data security. Follow-up information was collected at 3-month intervals over a 12-month period.

Statistical analysis

A descriptive initial analysis was performed on baseline characteristics and achievement of LDL-C goals as defined in the 2011, 2016, and 2019 ESC/EAS guidelines. This analysis corresponds to an assessment of the first 1,788 patients, based on a review of 10,872 medical records as of the data cutoff. The study uses a non-probabilistic convenience sampling approach, with an expected total sample size of 5,000 patients, distributed across at least 10 high-complexity institutions in Colombia. Each participating center is expected to contribute approximately 300 to 500 patients, depending on the availability of eligible cases. LDL-C goals were defined according to the respective ESC/EAS guidelines periods: <70 mg/dL for the 2011 and 2016 guidelines, and <55 mg/dL for the 2019 guideline. Frequencies and proportions were used for categorical variables, while measures of central tendency and dispersion were reported for quantitative variables. Normality of distribution was assessed using the Kolmogorov-Smirnov test. All statistical analyses were conducted using RStudio 2024.12.0 + 467 (R Foundation for Statistical Computing, Vienna, Austria). Figures were created using Python (matplotlib library, version 3.x).

Results

For this analysis, 1,788 patients from 11 medical institutions in Colombia were included. The median age was 66 years (IQR: 59–74), with a similar age distribution across all guidelines-based groups. Most of the population was male, comprising 70.7% of the sample (Table 1).

Regarding comorbidities, hypertension (HTN) was the most prevalent, affecting 67.5% of patients overall. Its prevalence was particularly high among patients in the 2011 ESC/EAS guideline group, where 75.8% had HTN. The overall prevalence was 40.8% for overweight, 18.9% for obesity, and 27.4% for diabetes mellitus (DM). Overweight increased from 28.6% in the 2011 group to 33.3% in the 2016 group, then declined to 27.9% in the 2019 cohort. Obesity rose steadily from 12.1% in the 2011 group to 14.9% and 20.9% in the 2016 and 2019 cohorts respectively. DM increased from 22% in the 2011 group to 29.9% in the 2016 group, before decreasing to 26.4% in the 2019 cohort. Comorbidities with lower frequencies are described in Additional file 1, Table S1.

Among the clinical indications for performing coronary angiogram, NSTEMI had the highest representation (29.1%), with a slight increase in the 2011 guideline group (35.2%). Unstable angina followed in frequency (24.9%), also peaking in the 2011 guideline group (35.2%). STEMI accounted for 20.7%, with some fluctuation across guidelines and being higher (23.6%) in the 2016 guideline cohort. Stable angina represented 12.9% of the indications, showing greater variation and an increase to 18.3% in the 2016 guideline group (Table 1).

LLT prescribed at discharge after the coronary angiogram varied across the different guidelines periods evaluated. Statins were the most frequently prescribed LLT, with an overall usage of 84.1%, reaching a peak of 89.3% in the 2016 guideline group. High-intensity statin regimens were prescribed in 91% of cases, following an upward trend and peaking at 96.9% under the 2019 guideline period. Ezetimibe use was limited overall (5.5%) but increased in the 2019 guideline group (7.9%). Fibrates were prescribed to 1.2% of patients, predominantly in the 2019 guideline group (1.3%). PCSK9i were rarely used, with a prescription rate of 0.4% exclusively under the 2019 guideline group. Notably, 4.7% of patients were discharged without any LLT, with the highest proportion observed in the 2019 guideline cohort (5.7%) (Table 1).

Table 1 Baseline characteristics of patients stratified by ESC/EAS guidelines groups

At the final follow-up visit (median time: 6.8 months; IQR 3.7–9.9), 36.6% (95% CI: 34.3–38.8%) of patients had achieved LDL-C goals. The highest proportion was observed in the ESC/EAS 2016 group (42.3%, 95% CI: 37.9–46.8%), followed by the 2019 guideline group (36.2%, 95% CI: 33.5–38.9%). Among patients with one follow-up (n = 1,084), 32.9% achieved LDL-C goals, with the highest proportion in the ESC/EAS 2016 group (41.1%). With two follow-ups (n = 503), 41% of patients achieved goals, with the ESC/EAS 2019 group showing the greatest improvement (42.3%). For patients with three (n = 176) and four (n = 25) follow-ups, the overall proportions achieving LDL-C goals were 45.5% and 44%, respectively. When assessed according to the ESC/EAS 2019 guideline, these proportions were 44.7% and 44.4%, respectively. A detailed breakdown of these findings is provided in Table 2.

The relative change in LDL-C, defined as the difference between the last and first available measurements during follow-up after coronary angiogram, became more pronounced with a higher number of follow-up measurements across the total population. This pattern was observed in both the 2011 and 2019 guidelines cohorts. In the 2011 guideline group, the relative change indicated a reduction of 0.3% after two follow-ups, which became more marked after three follow-ups, reaching 7.7%. In the 2019 guideline cohort, the reduction progressed from 5.6% after two follow-ups to 9.8% after three and reached 31.1% after four follow-ups — representing the most substantial LDL-C reduction among all cohorts (Table 2).

Among the total cohort, overall goal achievement ranged from 33.1% in the first follow-up window (first trimester post-coronary angiogram) to 37% and 36.7% in the third and fourth windows, respectively. Patients following the ESC/EAS 2016 guideline consistently demonstrated the highest achievement rates across all follow-up windows, with 44.2% in the first window, 45.3% in the second, 40.2% in the third, and 40.6% in the fourth. In contrast, patients under the ESC/EAS 2011 guideline had the lowest achievement rates, particularly in the later windows, with values as low as 6.7% in the final follow-up window. Achievement for the ESC/EAS 2019 group was moderate and like the overall cohort, ranging from 30.4 to 38.6% (Table 2).

Table 2 LDL-C goal achievement by guideline group, follow-up number and timing

Regarding LDL-C levels, the mean LDL-C in the total population at the end of follow-up was 73.5 mg/dL (± 33.8). Differences were observed between groups, with the highest level in the 2011 guideline group (95.8 mg/dL ± 31.3) and the lowest in the 2019 guideline group (69.5 mg/dL ± 32.3). Among patients who achieved LDL-C goals, the mean LDL-C level was 44.4 mg/dL ± 12.4, with the lowest concentration observed in those treated under the 2019 guideline (41.5 mg/dL ± 10.4) and the highest in the 2011 guideline group (52.2 mg/dL ± 13.6). In patients who did not reach LDL-C goals, the mean LDL-C concentration was 90.3 mg/dL, with the highest levels appearing in both 2011 (101.8 mg/dL) and 2016 guidelines groups (100.9 mg/dL), while the lowest concentration was found in the 2019 group (85.4 mg/dL) (Fig. 2).

Fig. 2

LDL-C levels based on goal achievement at the end of follow-up. ESC/EAS: European Society of Cardiology/European Atherosclerosis Society, LDL-C: low-density lipoprotein cholesterol

Across the guidelines groups, statins remained the most prescribed medication at the end of follow-up, covering 99.1% of cases. High-intensity statin regimens were prescribed in 89.8% of patients, with the highest proportion observed in the 2019 guideline group (95.2%). Atorvastatin was the most widely used statin overall (57.1%), followed by rosuvastatin (38.7%). In the 2011 guideline group, statin use reached 100%, with lovastatin as the predominant choice (58.2%), followed by atorvastatin (31.9%). By 2016, 99.6% of patients received statins, with atorvastatin (85.2%) and rosuvastatin (13.1%) as the main choices. Lovastatin use dropped to just one patient (0.2%) in the 2016 guideline group. In the 2019 guideline cohort, statin prescriptions remained high at 98.9%, though atorvastatin use declined to 48% as rosuvastatin increased to 51.2% (Table 3).

Regarding dosage patterns, the most common statins prescribed were atorvastatin and rosuvastatin, which showed distinct temporal trends. Among patients receiving treatment before the coronary angiogram, atorvastatin 40 mg/day was the most frequently used dose (68.7%), though its use declined at discharge (47.0%) and then rose again at follow-up (56.1%). In contrast, atorvastatin 80 mg/day showed a marked increase from pre-coronary angiogram (10.9%) to discharge (47.8%), followed by a reduction at follow-up (36.3%). For rosuvastatin, the highest dose (40 mg/day) was already common before the angiogram (67.1%) and increased progressively at discharge (79.9%) and follow-up (82.5%). Dosing patterns for other statins are detailed in Fig. 3, and non-statin LLT are presented in Table S2 of the supplementary material.

Among non-statin LLT, ezetimibe was the most frequently prescribed (17.2% overall) at the end of follow-up, with an uptake at 4.4% in 2011, 3.8% in 2016, and 23.4% in 2019. Fibrates were infrequently prescribed, accounting for 2.2% of overall cases, with fenofibrate being the most common fibrate in all evaluated guidelines groups (100%, 63.6% and 96.4% for 2011, 2016 and 2019 ESC/EAS guidelines, respectively). PCSK9i were only prescribed in the 2019 guideline cohort, accounting for 2.2% of those patients and 1.5% of the total population, with alirocumab being the most prescribed (55.6%). Omega-3 fatty acids were minimally prescribed, totaling only 0.5% (Table 3).

Table 3 LLT at the end of follow-up across ESC/EAS guidelines periods

Fig. 3

Heatmap of statin utilization by dose and timepoint. Pre-CA: Pre-Coronary Angiogram

Discussion

Our study provides a comprehensive evaluation of LDL-C goal achievement in very high CVR Colombian patients. To our knowledge, this is one of the largest studies in Colombia and Latin America assessing this outcome in patients with CAD, offering valuable insights into current national and regional practices. While statins remain the primary LLT, lipid management has gradually expanded with greater use of ezetimibe and PCSK9 inhibitors. However, the implementation of non-statin therapies remains limited, despite their importance in achieving stricter LDL-C targets. Our findings also highlight the role of follow-up frequency in optimizing LLT effectiveness. Despite these considerations, LDL-C goal achievement remains suboptimal.

Our cohort predominantly consisted of elderly patients, consistent with well-established evidence identifying age as a major risk factor for atherosclerosis [29]. Studies such as the START registry and DA VINCI study closely align with our findings [30, 31]. Additionally, the male predominance in our cohort is similar to the sex distribution in those studies [30, 31]. Men are known to exhibit a higher prevalence and extent of atherosclerotic plaque, while women often present with diffuse disease, complicating diagnosis and potentially lowering its reported prevalence [32]. This sex distribution, also observed in Colombian cohorts, appears to have clinical implications, as male patients appear to exhibit higher MACE outcomes [33]. Lastly, the high prevalence of HTN, overweight, obesity, and DM in our cohort supports their well-established association with ASCVD [34, 35].

Discharge after a coronary angiogram is a key moment to optimize LLT management, and it is recommended to initiate high-intensity statins as soon as possible, regardless of baseline LDL-C levels [36]. Nevertheless, a significant proportion of patients do not receive this therapy upon discharge, missing a crucial opportunity for secondary prevention [37]. In our cohort, 84.1% of patients were prescribed statins at discharge, a higher rate than in a retrospective US study across 12 hospitals, where only 70.8% received statins within 21 days of an acute coronay syndrome (ACS) event. Notably, just 48.9% received high-intensity statins in that study, reflecting significantly lower use [38]. Despite high statin prescription rates at discharge, many patients did not reach LDL-C targets, suggesting that factors such as access or adherence may play a role. Nonetheless, the increasing use of high-intensity statins—peaking in the 2019 guideline group—likely reflects growing physician awareness and implementation of ESC/EAS recommendations.

At follow-up, most patients in our cohort were also receiving statins, mainly high-intensity regimens, underscoring their central role in long-term lipid management. This aligns with large studies like a Swedish cohort of 26,768 patients with established ASCVD, where statins remained the cornerstone therapy—used in 82% within 90 days of discharge and 86% after one year [39]. In our cohort, statin and high-intensity regimen use were higher—likely influenced by the inclusion criteria, which required LLT prescription after follow-up angiogram. Nonetheless, both cohorts showed a steady increase in high-intensity statin use, suggesting a broader shift toward improved implementation of the guidelines. Notably, the widespread use of lovastatin in Colombia and its subsequent decline could be related to its initial inclusion in the national healthcare coverage system, followed by the later incorporation of more effective statins that enabled better achievement of LDL-C goals [40].

A decline in high-dose atorvastatin, simvastatin, and lovastatin use was observed over time. This pattern may reflect clinical adjustments in response to hepatic or muscular adverse effects, prompting physicians to reduce dosing in some patients [41]. Notably, 80 mg/day doses of simvastatin and lovastatin were prescribed in some patients. Given that the cohort included individuals treated as early as January 2011, before the FDA’s warning issued in June of that year, the use of high doses may be explained by the fact that these prescriptions preceded the updated safety recommendations [42].

Despite guideline consensus supporting ezetimibe and PCSK9i combined with high-intensity statins to improve LDL-C goal achievement, its use remains low in routine care [43]. The DA VINCI study, for example, reported that only 9.3% and 1.2% of patients were on ezetimibe or PCSK9i, respectively [31, 44], highlighting the gap between ESC/EAS guidelines recommendations and real-world implementation, particularly in very high CVR populations. These therapies are also underused in Colombia, with a national study showing that only 0.8% of 103,624 eligible patients received ezetimibe [45]. Similarly, analysis of government health data identified only 7,431 PCSK9i prescriptions between 2019 and 2021, despite the high prevalence of CVD in the country [46, 47]. In contrast, an Italian study found that 74.5% of patients received ezetimibe combination therapy, suggesting that a more structured healthcare system may facilitate its use. In contrast, PCSK9i use remained low, highlighting the global challenge of adopting this newer therapy [48]. Nevertheless, part of the limited uptake may also be explained by the inclusion of years prior to PCSK9i availability in our analysis period.

These dynamics may be partly explained by systemic factors such as fragmentation of the healthcare system, disparities between insurance schemes, and out-of-pocket costs, all of which may ultimately impact prescribing practices [49, 50]. For instance, a Colombian study reported that 11.3% of elderly patients received at least one potentially inappropriate cardiovascular medication, according to the Beers criteria, which encompass several commonly used drugs in older adults [51]. In a separate analysis, 15.9% of patients with CVD had potential prescribing omissions based on STOPP/START criteria [52]. These results reveal persistent gaps in the quality of prescribing even for basic cardiovascular therapies, raising concerns about the feasibility of implementing more complex treatment strategies or drug combinations, such as ezetimibe or PCSK9i.

Although statin use was high, with a substantial proportion receiving high-intensity regimens, LDL-C goal achievement at the last follow-up remained relatively low and varied depending on the guideline used, aligning with several reports showing suboptimal LDL-C target attainment worldwide. The START registry reported a target attainment rate of 58.1%, which, although higher than in our study, remained suboptimal. Notably, when applying the more stringent 2019 guideline threshold, this rate dropped to 38%, closely aligning with the proportion observed in our cohort [30]. A multicenter cross-sectional study from Portugal involving 8,288 patients with ASCVD reported significantly lower LDL-C goal achievement compared to our findings, with only 18% and 7% of patients meeting the 2016 and 2019 ESC/EAS thresholds, respectively [53]. Similarly, a study of 650 post-myocardial infarction patients found that just 34% and 11.7% reached LDL-C goals of 70 mg/dL and 55 mg/dL, respectively—both lower than in our study [54]. Comparable findings were reported in the INTERASPIRE study, an international study of patients with coronary heart disease conducted across 14 countries. Despite 86% receiving LLT, only 16.2% of Colombian participants achieved the LDL-C goal of < 55 mg/dL [55]. Finally, a study of 5,888 patients found a similar pattern in primary and secondary prevention for those at very high CVR. In this study, target achievement also declined from 2016 to 2019, regardless of statin intensity or the addition of non-statin therapies like ezetimibe and PCSK9i [31].

In the US, a cohort of patients with CAD followed after coronary angiogram demonstrated LDL-C goal achievement rates under the 2016 ESC/EAS guideline of 53.9% at three months, 57.6% at six months, and 53.2% at 12 months. For the stricter 2019 ESC/EAS guideline, the rates were 32.8%, 27.3%, and 32.5% at three, six, and 12 months, respectively, reflecting stability over time for the 2016 threshold and minor fluctuations for the 2019 threshold [56]. Similarly, in our cohort, LDL-C target achievement rates under the 2016 ESC/EAS guideline were 44.2% at three months, 45.3% at six months, and 40.6% at 12 months. For the stricter 2019 ESC/EAS guideline, the rates were lower, starting at 30.4% at three months and increasing slightly to 36.5% at six months and 38.6% by 12 months. These results demonstrate the sustained difficulty in achieving LDL-C targets that persists over time, particularly under more stringent guidelines, while showing relatively stable achievement patterns throughout the follow-up period.

However, the number of follow-up measurements performed during that period appears to play a crucial role in achieving LDL-C goals in patients with CAD. In a cohort reported by Waldeyer et al., with a median follow-up of 353 days, 42% had only one LDL-C measurement, while 29% had two and 29% had three, reflecting a relatively balanced distribution across these groups [57]. A different pattern emerged in our population, where 60.6% of patients had only one follow-up measurement, 28.1% had two, 9.8% had three, and just 1.4% had four follow-ups in a 12-month period. Despite these variations, a clear trend was observed in both study populations: the proportion of patients achieving LDL-C targets increased progressively with the number of follow-ups, reaching 45.5% with three follow-ups in our population and 44.7% in the previously mentioned study. Moreover, greater reductions in LDL-C levels were observed as follow-up frequency increased. For example, in patients without CVR stratification, more frequent LDL-C monitoring was associated with a reduction of 12.9 mg/dL in men and 13.5 mg/dL in women after six follow-up visits [58]. Similarly, in post-ACS patients, those who underwent more frequent follow-up during the first year achieved substantially better LDL-C control at one year compared to those with only a single 12-month visit [59]. These findings underscore the importance of regular LDL-C monitoring as a key determinant of goal achievement.

Despite the importance of follow-up frequency in achieving LDL-C targets, adopting frequent monitoring strategies may entail substantial healthcare costs. Even the Canadian Cardiovascular Society’s conservative approach—testing every 3–5 years or annually depending on risk—would require 3.6 million extra tests and 52.2 million Canadian dollars [60]. In contrast, for very high CVR patients such as those in our cohort, the ESC/EAS 2019 guidelines advocate more frequent assessments, which could place an even greater financial burden on healthcare systems [3]. Nonetheless, given its value in achieving LDL-C goals, follow-up frequency warrants further investigation and optimization to improve its cost-effectiveness.

LDL-C levels play a crucial role in reducing CVR and improving long-term outcomes in patients with CAD. In a retrospective study of 1,360 patients treated for MI, the average LDL-C level one year after discharge was 72 ± 23 mg/dL in the total population, a value similar to that observed in our cohort (73.5 ± 33.8 mg/dL). Among patients who achieved LDL-C goals, the levels were lower in our cohort (44.4 ± 12.4 mg/dL) compared to the previous study (52 ± 11 mg/dL); conversely, among those who did not reach targets, LDL-C levels were higher in our cohort (90.3 ± 30.6 mg/dL vs. 84 ± 21 mg/dL) [61]. While overall LDL-C levels were similar between cohorts, patients who achieved therapeutic targets in our study had a favorable lipid profile.

The low LDL-C goal achievement rates may stem from several factors, with patient adherence being a key one. Research shows that about 50% of patients with chronic illnesses do not take their medications as prescribed [62, 63]. Common reasons for discontinuation or refusal include fear of side effects, perceived adverse effects, and concerns about statin safety—factors that likely compromise LLT adherence and LDL-C control [41]. In addition, unhealthy lifestyle habits may substantially affect LDL-C control. A multicenter study across 27 countries involving 8,261 patients with CAD found that 19% had a history of smoking, with 55% being persistent smokers. Moreover, 32% were obese, and 41% had no intention to lose weight within six months. Regarding physical activity, 42% did not engage in regular exercise and had no plans to start [64]. The low availability and accessibility of statins in upper and lower middle-income countries, as well as in South America, may impact goal attainment and should be carefully considered, given their association with MACE outcomes and increased all-cause mortality [23, 65, 66]. Additionally, the COVID-19 pandemic may have worsened this issue in 2021–2022 by disrupting healthcare services and limiting medication access [67, 68]. Finally, factors such as inadequate statin intensity, clinical inertia, and ineffective patient-physician communication may also impact these observations [53].

Furthermore, a consistent decline in LDL-C goal achievement has been observed when applying the stricter 55 mg/dL threshold, both in our study and in others. Despite well-established recommendations, meeting the LDL-C goal set by the 2019 ESC/EAS guideline remains challenging with conventional statin therapy, even when combined with ezetimibe. Data from the SWEDEHEART registry, which included over 25,000 recent MI patients, assessed the efficacy of various LLT. A Monte Carlo simulation showed that only 20% of patients on high-intensity statins achieved the LDL-C goal, rising to 28.5% with ezetimibe. Notably, adding PCSK9i in eligible patients increased achievement to approximately 90% [69]. Real-world data from the DA VINCI study support these findings, showing that among very high CVR patients, the decline in LDL-C goal achievement from the 2016 to 2019 guidelines was less pronounced in those receiving PCSK9i [31].

While these results highlight the efficacy of advanced LLT, authors suggest that achieving the 2019 LDL-C target would require widespread use of non-statin therapies, such as PCSK9i, in very high CVR patients. However, it would pose significant financial constraints, particularly for resource-limited healthcare systems [70, 71]. This could relate to our findings, where—despite a gradual increase in PCSK9i prescriptions over the years—their use remains relatively low compared to statin monotherapy. In fact, the limited availability of these agents in Colombia may further hinder LDL-C goal achievement, reflecting trends reported in previous studies and underscoring the broader challenges of implementing non-statin therapies in low- and middle-income settings.

Strengths and limitations

One strength of this study is its multicenter design, involving institutions from various regions of Colombia, and its relatively large sample size, which enhances the generalizability of findings. The 12-month follow-up with multiple measurements allows for a comprehensive assessment of LDL-C goal achievement and LLT use over time. The application of ESC/EAS guidelines ensures comparability with international studies. By analyzing three distinct time periods aligned with successive ESC/EAS guideline updates—reflecting evolving LDL-C targets, while applying consistent patient selection criteria—this study captures period effects reflecting changes in real-world clinical practice, while minimizing cohort effects. In a country where research resources are often limited, this study also reflects a significant national effort to establish collaborations and generate local evidence in CVR management. This research provides valuable insight into LLT usage and LDL-C control and may serve as a foundation for future large-scale registries and studies in similar healthcare systems.

However, this study has several limitations. First, the use of a non-probabilistic sampling approach limits the representativeness of the sample. This is an initial analysis based on an interim dataset, as patient recruitment is still ongoing. Additionally, the variables were obtained from medical records, which may contain incomplete or inaccurate information, potentially affecting data reliability. Given our inclusion criteria, there was significant heterogeneity in the number of follow-up visits among patients. The study was also limited to high-complexity centers in Colombia, which may restrict the external validity of the findings, particularly regarding their applicability to primary or secondary care settings and to other regions. Moreover, the limited inclusion of patients from the 2011 ESC/EAS group—likely due to data traceability issues—may have reduced the representativeness of that period. Furthermore, LDL-C was measured either directly or estimated using the Friedewald equation, potentially introducing variability in lipid profile assessments, particularly in patients with elevated triglyceride levels. LLT adherence and its potential determinants were not assessed, which may be relevant factors influencing LDL-C goal achievement. Finally, the absence of data from 2020 due to the COVID-19 pandemic limits the assessment of its actual impact on LDL-C control in patients managed under the 2019 ESC/EAS guideline.

Conclusions

Despite widespread LLT use, LDL-C goal achievement remains suboptimal, particularly under the more stringent 2019 ESC/EAS guideline. Those findings highlight the ongoing challenge of optimizing lipid control, emphasizing the importance of adherence, follow-up monitoring, and potentially greater use of combination therapies. The observed trend of improved LDL-C reduction with more follow-up assessments suggests that consistent patient monitoring plays a crucial role in treatment success. Future research should explore strategies to enhance adherence and evaluate the impact of emerging LLT in real-world clinical practice.