Uncontrolled Low-density Lipoprotein Cholesterol Research Articles

Real-World Exploration of LDL-Cholesterol Management in Patients with Atherosclerotic Cardiovascular Disease

BackgroundAlthough guidelines recommend low-density lipoprotein cholesterol (LDL-C) to be <70mg/dL in patients with atherosclerotic cardiovascular disease (ASCVD), the rate of achieving this goal remains suboptimal. We sought to understand real world contemporary practice patterns of LDL-C management in patients with ASCVD, and whether LDL-C testing influenced management across US health systems. MethodsA retrospective cohort study utilizing electronic medical record data from five health systems participating in the CardioHealth Alliance was performed on patients with an LDL-C measurement in 2021 and prior ASCVD. Multivariable regression modeling was used to determine the relationship of clinical factors with achievement of guideline directed LDL-C target. Changes in lipid lowering therapy (LLT) after LDL-C testing were also described. ResultsAmong 216,074 patients with ASCVD, 129,886 (60.1%) had uncontrolled LDL-C (i.e. ≥70 mg/dL). Compared with participants with controlled LDL-C (<70mg/dL), those with uncontrolled LDL-C were more frequently female (50.9% vs 35.1%), or Black (13.7% vs. 10.3%), and less commonly had coronary artery disease as the form of vascular disease (73.0% vs. 83.5% %), heart failure (21.3% vs. 29.1% %), diabetes (34.1% vs. 48.2%), atrial fibrillation (19.3% vs. 26.1%), or chronic kidney disease (25.1% vs. 32.2%). In multivariable analyses, the factors most strongly associated with failure to achieve LDL-C control were female sex (RR 1.13 [95% CI 1.12-1.14] p <0.001) and Black race (1.15 [1.14-1.17] p <0.001). Among the 53,957 (41.5%) of those with uncontrolled LDL-C ≥70 mg/dL not on lipid lowering therapy (LLT) at baseline, only 21% were initiated on any LLT within 6 months of the uncontrolled LDL-C value. ConclusionsWithin five diverse large health systems in the CardioHealth Alliance, more than half of the patients with ASCVD had uncontrolled LDL-C with significant disparities based on sex and race at baseline. The vast majority were not initiated on any lipid lowering therapy within 6 months of an elevated test result indicating persistent gaps in care that will likely worsen health inequities in outcomes. This highlights the urgent need for implementation efforts to improve equitable care.

EFFECT OF LOW-DENSITY LIPOPROTEIN (LDL) CHOLESTEROL VALUE ON NON-PROLIFERATIVE DIABETIC RETINOPATHY (NPDR) IN PATIENTS WITH TYPE II DIABETES MELLITUS (T2DM): A SYSTEMATIC REVIEW

Introduction &amp; Objectives : Type 2 Diabetes Mellitus (T2DM) is a metabolic disease in which the body is unable to control blood sugar levels and is characterized by hyperglycemia caused by lack of insulin action. One of the most common microvascular complications of DM that can cause blindness to sufferers is Diabetic Retinopathy (DR). One of the risk factors that can exacerbate the progression of T2DM is the level of Low-Density Lipoprotein (LDL). However, there are still differences of opinion in several studies if LDL has a significant role in the occurrence of DR. This study aimed to determine whether there is a relationship between the value of LDL cholesterol and the occurrence of Non-Proliferative Diabetic Retinopathy.&#x0D; Methods : Systematic review utilizing MeSH terminology and PICO methods were done for information extraction of online database, including PubMed, and Google Scholar by utilizing the following keyword “Low-Density Lipoprotein”, “Non-Proliferative Diabetic Retinopathy”, “Diabetes Melitus”. The extracted studies were then analyzed using the New-Castle Ottawa Scale (NOS).&#x0D; Results : In total, 2 eligible studies (103 subjects) were found. Dornan et al., stated that total cholesterol levels were higher in NPDR Patients (5.1 +/- 0.7 mmol/l, p ? 0,02) and Mursi et al., shows that in patients with uncontrolled LDL cholesterol, NPDR was found (53,7%, p &lt; 0,015). NOS was used to evaluate the quality of the studies and all studies showed to be in good quality.&#x0D; Conclusion : According to the results of this systematic review, there is a significant correlation between the degree of diabetic retinopathy and LDL cholesterol.

Quantifying the 'distance to LDC-goal' in patients at very high cardiovascular risk with hyperlipidaemia in Germany: a retrospective claims database analysis.

This study quantified the 'distance to LDL-C goal' in patients at very high cardiovascular risk with uncontrolled hyperlipidaemia. 'Distance to LDL-C goal' was defined as the percentage by which low-density lipoprotein cholesterol (LDL-C) levels needed to be reduced to achieve the LDL-C goals specified in the 2016 or 2019 European Society of Cardiology/European Atherosclerosis Society guidelines. This retrospective analysis using data from the IQVIA Disease Analyzer database included patients who were predominantly treated by a primary care physician, diabetologist or cardiologist between 2014 and 2018, with a diagnosis of hyperlipidaemia and an initial LDL-C measurement (index event) and one or more cardiovascular risk factors. The primary outcome was to assess the proportion of patients with uncontrolled hyperlipidaemia and to classify the 'distance to LDL-C goal' in these patients. Data from 32,963 patients were analysed (n = 27,159, n = 3873 and n = 1931 patients in the primary care physician, diabetology and cardiology cohorts, respectively). Most patients had uncontrolled LDL-C levels (⩾70 mg/dL; ⩾1.8 mmol/L) at index (91.0%, 86.4% and 94.0% of patients in the primary care physician, diabetology and cardiology cohorts, respectively). Analysis of the 'distance to LDL-C goal' indicated that approximately one-third of patients in each cohort required an LDL-C level reduction of up to 50% relative to index to achieve their LDL-C goal (35.8%, 43.7% and 28.4% of patients in the primary care physician, diabetology and cardiology cohorts, respectively). LDL-C control was not achieved at 36 months post-index in most patients with uncontrolled LDL-C levels (86.8%, 81.7% and 90.2% of patients in the primary care physician, diabetology and cardiology cohorts, respectively). LDL-C levels were uncontrolled in most patients with hyperlipidaemia. Analysis of the 'distance to LDL-C goal' showed that most patients required a substantial LDL-C level reduction to achieve their LDL-C goal.

Long-term secondary prevention and outcome following acute coronary syndrome: real-world results from the Swedish Primary Care Cardiovascular Database.

Most studies of treatment adherence after acute coronary syndrome (ACS) are based on prescribed drugs and lack long-term follow-up or consecutive data on risk factor control. We studied the long-term treatment adherence, risk factor control, and its association to recurrent ACS and death. We retrospectively included 3765 patients (mean age 75 years, 40% women) with incident ACS from 1 January 2006 until 31 December 2010 from the Swedish Primary Care Cardiovascular Database of Skaraborg. All patients were followed until 31 December 2014 or death. We recorded blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), recurrent ACS, and death. We used data on dispensed drugs to calculate the proportion of days covered for secondary prevention medications. Cox regressions were used to analyse the association of achieved BP and LDL-C to recurrent ACS and death. The median follow-up time was 4.8 years. The proportion of patients that reached BP of <140/90 mm Hg was 58% at Year 1 and 66% at Year 8. 65% of the patients reached LDL-C of <2.5 mmol/L at Year 1 and 56% at Year 8; however, adherence to statins varied from 43% to 60%. Only 62% of the patients had yearly measured BP, and only 28% yearly measured LDL-C. Systolic BP was not associated with a higher risk of recurrent ACS or death. Low-density lipoprotein cholesterol of 3.0 mmol/L was associated with a higher risk of recurrent ACS {hazard ratio [HR] 1.19 [95% confidence interval (CI) 1.00-1.40]} and death HR [1.26 (95% CI 1.08-1.47)] compared with an LDL-C of 1.8 mmol/L. This observational long-term real-world study demonstrates low drug adherence and potential for improvement of risk factors after ACS. Furthermore, the study confirms that uncontrolled LDL-C is associated with adverse outcome even in this older population.

Abstract 16059: Real-World Exploration of Low Density Lipoprotein Cholesterol Management in Patients With Atherosclerotic Cardiovascular Disease

Introduction: Although guidelines recommend low-density lipoprotein cholesterol (LDL-C) to bel &lt;70mg/dL in patients with atherosclerotic cardiovascular disease (ASCVD), implementation of these recommendations remains low. Research Question: To understand LDL-C management nationally and identify gaps or disparities in guideline directed care. Methods: A retrospective cohort study utilizing electronic medical record data from five health systems participating in the CardioHealth Alliance and PCORnet® was performed on patients with a LDL-C measurement in 2021 and prior ASCVD. Multivariable regression modeling was used to determine the relationship of clinical factors with guideline directed LDL-C targets. Results: Among 216,074 ASCVD participants, only 86,188 (40%) had LDL-C &lt;70 mg/dL. Compared with participants with uncontrolled LDL-C (≥70mg/dL), those with LDL-C &lt;70 mg/dL tended to be male (64.9% vs 49.1%), White (87.3% vs 83.9%), had coronary artery disease (83.5% vs 73.0%), heart failure (29.1% vs 21.3%), diabetes (48.2% vs 34.1%), and atrial fibrillation (26.1% vs 19.3%). Among those with LDL-C ≥70 mg/dL not on lipid lowering therapy (LLT) at baseline (n=53,957 [41%]), only 20% were initiated on any LLT within 6 months of the elevated LDL-C value. Several factors were associated with not achieving LDL-C &lt;70 mg/dL (Figure) including female sex (RR 1.13 [95% CI 1.12-1.14] p &lt;0.001), Black race (1.15 [1.14-1.16] p &lt;0.001), and Hispanic ethnicity (1.04 [1.01-1.06] p=0.007). Additionally, prior Lp(a) testing was associated with reaching LDL-C target (0.87 [0.82-0.92], p&lt;0.001). Conclusions: Within five large U.S. health systems, only 40% of ASCVD patients achieved target LDL-C of &lt;70 mg/dL. Patients who were female, Black, and/or Hispanic were particularly unlikely to achieve target, highlighting significant disparities. Multidisciplinary and inclusive approaches from health system to community may be needed to improve LDL-C care nationally.

Efficacy of Generic Formation of Ezetimibe in Patients with High Cardiovascular Risk Receiving High-Potency Statin

Background: Ezetimibe has been recommended to add on statin therapy when maximally tolerated statin cannot achieve low-density lipoprotein cholesterol (LDL-C) target. However, the safety and efficacy of generic formulation of ezetimibe has rarely been reported. Objective: To examine efficacy of branded generic ezetimibe in patients with high cardiovascular risk receiving high-potency statin. Materials and Methods: The present study was a prospective cohort study in adult patients with high cardiovascular risk receiving atorvastatin 40 mg/day, but the LDL-C level was still higher than 70 mg/dL. Branded generic ezetimibe 10 mg once daily (MiBEAZ™) was added on the highpotency statin therapy as a combination treatment. Lipid parameters were evaluated three months after ezetimibe treatment. Results: Of the 61 patients, mean age was 62.4±11.5 years, and 33 (54.1%), were male. Coronary artery disease was reported in 58 patients or 95.1%. The median baseline of LDL-C was 95.0 mg/dL (IQR 79.5, 108.5). At 3-month follow-up, total cholesterol and LDL-C levels were significantly decreased by branded generic ezetimibe add-on therapy. The relative change of LDL-C reduction was 26.3% (IQR –38.8, –11.1, p&lt;0.001). The LDL-C target under 70 mg/dL was attained in 60% of the patients. Triglyceride and high-density lipoprotein cholesterol levels remained unchanged. After ezetimibe medication, there were no differences in renal or hepatic function. Conclusion: The authors demonstrated that branded generic ezetimibe significantly reduced levels of LDL-C in high cardiovascular risk patients with uncontrolled LDL-C level despite the high-potency statin treatment. There was no concern regarding safety issues with the branded generic ezetimibe add-on therapy. Keywords: Low-density lipoprotein cholesterol; Generic ezetimibe; Lipid-lowering; Dyslipidemia

Optimal lipid-lowering therapy in patients who were functionally deferred percutaneous coronary intervention

Deferral of percutaneous coronary intervention (PCI) for functionally insignificant stenosis, defined as fractional flow reserve (FFR) > 0.80, is associated with favorable long-term prognoses. The lower-the-better strategy for low-density lipoprotein cholesterol (LDL-C) management is an established non-angioplasty therapy to improve the clinical outcomes of patients undergoing PCI. We examined the optimal LDL-C management in cases of intermediate coronary stenosis with deferred PCI on the basis of FFR values. This observational study included 273 consecutive patients with a single target vessel and deferred PCI with an FFR > 0.80. Patients with an FFR of 0.81–0.85 (n = 93) and those with FFR > 0.85 (n = 180) were classified into the lower (< 100 mg/dL) and higher (≥ 100 mg/dL) LDL-C groups. The endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including death, non-fatal myocardial infarction, ischemic stroke, heart failure hospitalization, and unplanned revascularization. Patients with an FFR of 0.81–0.85 had a significantly higher MACCE rate than those with an FFR > 0.85 (log-rank, p = 0.003). In patients with an FFR of 0.81–0.85, the lower LDL-C group showed a significantly lower MACCE rate than the higher LDL-C group (log-rank, p = 0.006). However, the event rate did not differ significantly between the two groups in patients with FFR > 0.85 (log-rank, p = 0.84). Uncontrolled LDL-C levels were associated with higher MACCE rates in cases with deferred PCI due to an FFR of 0.81–0.85. This high-risk population for adverse cardiovascular events should receive strict LDL-C-lowering therapy.

Cardiovascular risk factor profile in patients admitted to a community-based cardiac rehabilitation program after one year: what risk factors are not being controlled?

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac rehabilitation (CR) is a multidisciplinary intervention designed to reduce cardiovascular (CV) risk, encourage healthy behaviors, reduce physical impairment, and promote an active lifestyle. After completing a phase II CR program, it is important to maintain long-term CV risk factor control. However, many patients do not achieve or maintain lifestyle and risk factor targets on a long-term basis. Therefore, it is of interest to understand which risk factors are not reaching the targets to better understand and personalize long-term community-based CR programs. Purpose To characterize the modifiable CV risk factors profile in coronary artery disease (CAD) patients admitted to a community-based phase III CR program, including lipid profile, overweight/obesity, physical activity (PA) and sedentary behaviour (SB), at the beginning and after completing the first year of the CR program. Methods This retrospective cohort study included CAD patients that attended for 1-year a community-based phase III CR program. At the beginning (M0) and after one year (M1) of the CR program, all patients performed a risk profile assessment including: Lipid profile [total cholesterol (total-c), high density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL)], body mass index (BMI), PA and SB. BMI was assessed with the patient's weight in kilograms divided by the square of height in meters and lipid profile values were obtained from blood testing. PA and SB were objectively measured by using an accelerometer. All participants attended supervised exercise sessions, 3x week, 60 mins, including aerobic and resistance exercises, 3 educational sessions and a nutritional counseling consultation per year. Results In the sample of 159 patients at baseline (81.8% male, mean age 61±10 years, BMI: 28.3±4.3 kg/m²), overweight and obesity proved to be the most prevalent risk factor (80.7%), followed by uncontrolled LDL levels (74.8%). After a 1-year intervention (n=48, 90% male, mean age 62±10 years), LDL levels were kept above the targets (M0: 73.3±28.9 mg/dL and M1: 68.6±19.6 mg/dL, p=0.186), BMI did not change (M0: 27.5±3.9 kg/m² and M1: 27.8±4.0 kg/m², p=0.168) and SB remained high (M0: 11.50±2.90 hours/day and M1: 11.58 ± 2.71 hours/day, p=0.908). Although, moderate to vigorous PA (MVPA) decreased (M0: 343±195 mins/week and M1: 293±164 mins/week, p&amp;lt;0.001), participants were still on target, between 150 to 300 mins MVPA week. Conclusion Our findings show that after a 1-year of a phase III CR program intervention CVD patients maintained MVPA recommended levels, but did not reach body composition, lipid profile, and SB targets. Future strategies should be implemented in long-term CR programs to better control LDL, body composition and SB.

Achievement of the ESC recommendations for secondary prevention of cardiovascular risk factors in high-risk patients with type 2 diabetes: A real-world national cohort analysis

AimTo assess compliance with European Society of Cardiology (ESC) secondary prevention recommendations in a nationwide contemporary population with diabetes mellitus (DM) and coronary artery disease. MethodWe conducted a retrospective observational study using linked health data in patients across Wales with DM undergoing percutaneous coronary intervention (2012–2017). The follow-up was for one year. We analysed the clinical characteristics, medications, target levels for HbA1c, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and blood pressure against the ESC prevention guidelines. ResultsOverall, 3478 patients with diabetes had available data at 1-year post-PCI. Only 43% had HbA1c levels <53 mmol/L, but 81% had blood pressure < 140/80 (current ESC targets).Prescribing frequency of the newer hypoglycaemic agents (glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors) was suboptimal, with a higher rate in patients with HbA1c ≥53 mmol/mol.Only 51% & 27% of the patients had LDL-C levels <1.8 &1.4 mmol/L (2016 & 2019 guidelines recommendations respectively), and 55% & 34% had non-HDL-C levels <2.6 & 2.2 mmol/L (2016 & 2019 guidelines respectively). Of the uncontrolled LDL-C patients, 42% (2016 target) and 35% (2019 target) were prescribed high-intensity statins. Females were more likely to have LDL-C targets above the recommended level. ConclusionAchievement of ESC treatment goals in this very-high risk cohort for DM and hyperlipidaemia was far from optimal, with a low prescription rate of the guidelines-recommended therapy. Target goals for hypertension were met more frequently. An up-to-date analysis reflecting the current practice against the most recent guidelines is warranted.

Lost Therapeutic Benefit of Delayed Low-Density Lipoprotein Cholesterol Control in Statin-Treated Patients and Cost-Effectiveness Analysis of Lipid-Lowering Intensification

ObjectivesAttainment of low-density lipoprotein cholesterol (LDL-C) therapeutic goals in statin-treated patients remains suboptimal. We quantified the health economic impact of delayed lipid-lowering intensification from an Australian healthcare and societal perspective. MethodsA lifetime Markov cohort model (n = 1000) estimating the impact on coronary heart disease (CHD) of intensifying lipid-lowering treatment in statin-treated patients with uncontrolled LDL-C, at moderate to high risk of CHD with no delay or after a 5-year delay, compared with standard of care (no intensification), starting at age 40 years. Intensification was tested with high-intensity statins or statins + ezetimibe. LDL-C levels were extracted from a primary care cohort. CHD risk was estimated using the pooled cohort equation. The effect of cumulative exposure to LDL-C on CHD risk was derived from Mendelian randomization data. Outcomes included CHD events, quality-adjusted life-years (QALYs), healthcare and productivity costs, and incremental cost-effectiveness ratios (ICERs). All outcomes were discounted annually by 5%. ResultsOver the lifetime horizon, compared with standard of care, achieving LDL-C control with no delay with high-intensity statins prevented 29 CHD events and yielded 30 extra QALYs (ICERs AU$13 205/QALY) versus 22 CHD events and 16 QALYs (ICER AU$20 270/QALY) with a 5-year delay. For statins + ezetimibe, no delay prevented 53 CHD events and gave 45 extra QALYs (ICER AU$37 271/QALY) versus 40 CHD events and 29 QALYs (ICER of AU$44 218/QALY) after a 5-year delay. ConclusionsDelaying attainment of LDL-C goals translates into lost therapeutic benefit and a waste of resources. Urgent policies are needed to improve LDL-C goal attainment in statin-treated patients.

Association between baseline serum uric acid and development of LDL-C level in patients with first acute myocardial infarction

BackgroundData on the relationship of baseline serum uric acid (SUA) with development of low-density lipoprotein cholesterol (LDL-C) level in patients with first acute myocardial infarction (AMI) are limited. The present study is to evaluate whether elevated SUA predicts the development of LDL-C in the first AMI.MethodsThis is a retrospective 6-month cohort study of 475 hospitalized Chinese patients who underwent first AMI between January 2015 and December 2019 and were reevaluated half a year later at the Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Jiangxi Province, China. The associations of baseline SUA with the percentage decrease of LDL-C (%) and LDL-C control were analyzed by using logistic regression analyses, multivariate linear regression analyses and the restricted cubic spline.ResultsOver the 6-month follow-up, baseline SUA was independently and positively associated with the percentage decrease of LDL-C (%) and LDL-C control in a dose response fashion. After multivariable adjustment, per SD increment of baseline SUA (120.58 μmol/L) was associated with 3.96% higher percentage decrease of LDL-C(%). The adjusted OR (95% CI) for LDL-C control was 5.62 (2.05, 15.36) when comparing the highest tertile (SUA ≥ 437.0 μmol/L) to the lowest tertile (< 341.7 μmol/L) of baseline SUA.ConclusionsAmong Chinese patients with first AMI, higher baseline SUA was associated with higher LDL-C deduction percentage (%), and higher rate of LDL-C control in the short-term follow-up, respectively. SUA acquired when AMI occurred was prone to be profitable in predicting the risk stratification of uncontrolled LDL-C and dyslipidemia management.

A real-world assessment of treatment patterns in patients with atherosclerotic cardiovascular disease with hypercholesterolemia: a retrospective database analysis in Germany

Abstract Background The European Society of Cardiology (ESC) guidelines suggest that greater absolute reduction in low-density lipoprotein cholesterol (LDL-C) leads to greater cardiovascular risk reduction. Several lipid-lowering treatments (LLTs) are available in Germany; however, the research on treatment patterns and LDL-C outcomes among patients (pts) receiving LLTs in real-world setting is limited. Purpose To characterize the pts characteristics, treatment patterns and LDL-C outcomes of pts with atherosclerotic cardiovascular disease (ASCVD) with hypercholesterolemia (ASCVD-H) in Germany. Methods This is a descriptive, non-interventional, retrospective cohort study of ASCVD-H pts identified from general physician (GP) practices available in the electronic medical record (EMR) database Disease Analyzer (January 1992-June 2020) in Germany. ASCVD-H pts were included if they had a recorded diagnosis, were prescribed LLTs or had LDL-C levels of ≥55 mg/dL anytime within 6 months before and 3 months after the index date (ID), as per the data recorded by the participating physician. The first encounter of ASCVD after hypercholesterolemia during the identification period (1/07/2015–30/06/2019) was considered as the ID. Persistence was measured as the duration (in days) with allowed gap of 60 days and adherence as proportion of days covered (PDC) within 12 and 24 months after ID. Results We included 147,905 pts with ASCVD-H (57.2% male; mean age: 70.6 yrs; ≥75 yrs-old: 43.3%; mean BMI: 29.0 kg/m2). Coronary artery disease was the most common index diagnosis (73.2%), followed by cerebrovascular disease (31.7%) and peripheral vascular disease (21.5%). Hypertension (83.5%) and diabetes (27.6%) were the most common comorbidities among these pts. At ID, statin monotherapy (58.6%) was the most commonly prescribed LLT, with simvastatin being the most common drug (36.4%). The use of PCSK9 inhibitors, ezetimibe and fibrates was very limited (&amp;lt;1%; Table 1). Of note, LDL-C measurements (6 months prior and 3 months post index) were available for 50.7% of pts. In pts with uncontrolled LDL-C (≥55 mg/dL), 47.9% were receiving statin monotherapy (28.6% were on simvastatin), whereas there was no LLT prescribed in 48.0% of pts. The mean (SD) persistence and adherence to statins monotherapy within 24 months follow-up was 522 (260) days and 0.721 (0.345), respectively, with 60% of pts being adherent (PDC ≥0.80) to statins monotherapy. Conclusions Pts with ASCVD-H in Germany treated by GPs are elderly pts with multiple cardiovascular comorbidities. LDL-C was measured in nearly half of the pts, and almost all had LDL-C ≥55 mg/dL at ID. Findings indicate low prescription of LLTs in GP setting, particularly non-statin LLTs. The mean adherence (PDC) to statin monotherapy was 72% within the 24-month after ID. Data suggest the need for newer therapies with potential to control LDL-C levels. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novartis Pharma AG, Basel, Switzerland.

Treatment patterns in patients with Familial hypercholesterolemia: evidence from real-world studies in Germany and the UK

Abstract Background Familial hypercholesterolemia (FH) includes a spectrum of disease as per the number and effect of mutations in specific proteins involved in low-density lipoprotein cholesterol (LDL-C) metabolism, together with other genetic factors. Elevated LDL-C levels have been strongly associated with risk of cardiovascular and coronary heart disease, with up to 10-fold risk in patients (pts) with FH than without FH. The aim of lipid-lowering treatments (LLTs) is to reduce the LDL-C levels, although there is limited research describing treatment patterns and LDL-C outcomes in FH pts in routine care. Purpose To characterize the treatment patterns and LDL-C outcomes of FH pts in the real-world setting in Germany (GER) and the UK. Methods We conducted two descriptive, non-interventional and retrospective cohort studies. Pts in GER were identified from General Physician (GP) and Cardiology practices available in electronic medical records database Disease Analyzer (January 1992-June 2020). Pts in the UK were identified from the Clinical Practice Research Datalink linked to the Hospital Episode Statistics admitted pts care and Office of National Statistics datasets. Pts were included if they had diagnosis of FH (index date [ID]) and data available within 6-month before and 3-month after the ID. The first diagnosis of FH in the identification period (GER, 1/07/2015–30/06/2019; UK, 01/01/2010–31/05/2018) was considered the ID. Persistence and adherence to the recorded LLT at ID was analyzed for pts with at least 12 months and 24 months of follow-up. Persistence was measured as the duration (in days) with allowed gap of 60 days and adherence as proportion of days covered (PDC). Results Analysis included 2,105 FH pts from GER and 9,846 from the UK. Data are presented as GER/UK. The mean (SD) age of pts was 60 (15)/52 (14) years, and 60%/61% were females. Hypertension (53%/27%) and depression (31%/38%) were the common comorbidities. At ID, statin monotherapy (29%/68%) was the most commonly prescribed LLT. The use of ezetimibe, fibrates and PCSK9 inhibitors was very low in both countries (Table 1). Of note, LDL-C measurements at ID (−6m/+3m) were available for 31%/73% of pts. In pts with uncontrolled LDL-C (≥55 mg/dL), 34%/64% were receiving statin monotherapy, whereas there was no use of LLT in 62%/29% of pts. During the 24 months follow-up, the mean (SD) persistence and PDC to statins monotherapy was 471 (264)/489 (289) days and 0.65 (0.36)/0.69 (0.46), respectively, with 50%/70% of pts being adherent (PDC ≥0.80). Conclusions In our study, in GER, the rate of LDL-C measurements was low. In both GER and UK, almost all measured patients had LDL-C ≥55mg/dL at ID. Findings indicate low prescriptions of LLTs in GP setting, particularly non-statin LLTs in both countries. The mean adherence (PDC) in GER and the UK was 65% and 69%, respectively within 24 months after ID. Improved LDL-C monitoring and new therapies with potential to lower LDL-C are warranted. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novartis Pharma AG, Basel, Switzerland

Practical Decision Algorithms for the Use of the Cardiovascular Polypill in Secondary Prevention in Europe.

The main objective of cardiovascular disease (CVD) prevention is to reduce morbidity and mortality. Despite recommendations on evidence-based pharmacological treatment and lifestyle changes, the control of CV risk factors such as hypertension or dyslipidaemia is not optimal. The use of a CV polypill, including guideline-recommended drugs, as a baseline therapy, may contribute to improving risk factors control either by improving the treatment adherence or by the synergistic effect of its components. The CNIC-Polypill is the first CV polypill approved in Europe as an effective strategy for secondary prevention, which contains acetylsalicylic acid, atorvastatin (in two optional doses), and ramipril (in three optional doses) in a single pill. The present practical clinical document aims to provide a guide for patient management after an acute coronary syndrome (ACS) or with chronic CVD (CCVD) with a strategy based on the CNIC-Polypill, also considering the need to add other therapies for a personalized treatment. The most suitable clinical scenarios for the CNIC-Polypill use are discussed: (a) in patients after an ACS at discharge, (b) in patients with CCVD (chronic coronary syndrome, stroke, or peripheral artery disease) with uncontrolled low-density lipoprotein cholesterol (LDL-c) and/or blood pressure levels and (c) in patients with CCVD with well-controlled risk factors to simplify treatment and reduce polypharmacy in the context of CCVD prevention.

Risk factor control after ischemic stroke or transient ischemic attack.

We aimed to estimate the status of risk factor control after ischemic stroke or transient ischemic attack (IS/TIA), and the influence on recurrent stroke in rural communities of northeastern China. This population-based, prospective cohort study enrolled adults aged ≥35years residing in rural northeastern China. We conducted cardiovascular health examinations in 2012-2015 and followed up in 2018 to record any cardiovascular event. Control of risk factors after IS/TIA was determined through a baseline survey. The Cox proportional hazard model was used to evaluate the relationship between uncontrolled risk factors and stroke recurrence. Of the 10,700 participants, 575 were diagnosed with IS/TIA and were included in the analysis. At baseline, the rates of control of risk factors were as follows: fasting plasma glucose (FPG), 81.6%; not currently smoking, 65.7%; and achieving physical activity targets, 61%. Blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), and body mass index (BMI) were poorly controlled (28.3%, 26.3%, and 37.4%, respectively). The rate of stroke recurrence was 12% during a median follow-up of 4.43years. After adjusting for age, sex, ethnicity, family history of stroke, and current drinking, uncontrolled BP and not achieving physical exercise targets were associated with an increased risk of recurrence (hazard ratios: 2.081, 1.685, respectively; p<.05). Uncontrolled FPG, BMI, or LDL-C and current smoking did not significantly influence recurrent risk (p>.05). Control of risk factors after IS/TIA needs to be improved in rural communities of northeastern China to prevent recurrence and thus alleviate the public health and economic burden of stroke.

Goal achievement of HbA1c and LDL-cholesterol in a randomized trial comparing colesevelam with ezetimibe: GOAL-RCT.

To compare the efficacy and safety of colesevelam and ezetimibe as second-line low density lipoprotein-cholesterol (LDL-c)-lowering options in type 2 diabetes (T2D). GOAL-RCT is a 24-week, open-label, randomized, pragmatic clinical trial. Subjects with T2D with uncontrolled HbA1c (7.1%-10%) and LDL-c (>2.0 mmol/L) were randomized 1:1 to colesevelam 3.75 g or ezetimibe 10 mg daily. The primary composite outcome was the proportion of participants achieving an LDL-c target of ≤2.0 mmol/L and HbA1c target of ≤7.0%. Intention to treat analysis was performed. Two hundred subjects were enrolled: mean age 59 ± 10 years; mean HbA1c 8.0%; mean LDL-c 2.5 mmol/L; 97% on statin therapy. The primary composite outcome was achieved by similar proportions of participants with colesevelam (14.6%) and ezetimibe (10.5%) (Pnon-inferiority < .001, Psuperiority = .41). LDL-c reduction from baseline was less with colesevelam compared with ezetimibe (14.0% vs. 23.2%, P < .01), as was the proportion of subjects achieving an LDL-c target of ≤2.0 mmol/L (47.6% and 67.0%, respectively; P = .007). Mean HbA1c was reduced with colesevelam (-0.26 ± 0.10%), while no change was observed with ezetimibe (difference P = .06). Adverse events and discontinuation rates were higher for colesevelam (20.2% and 31.1%) compared with ezetimibe (7.2% and 6.2%), respectively. Among subjects with T2D, the initiation of colesevelam or ezetimibe led to similar achievement of primary composite outcome (LDL-c and HbA1c within target), with ezetimibe recording a greater LDL-c reduction and better tolerability than colesevelam.

PCV17 BUDGET IMPACT ANALYSIS OF PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 INHIBITORS (PCSK9I) USE IN COMBINATION WITH STATINS FOR TREATMENT OF UNCONTROLLED LOW-DENSITY LIPOPROTEIN-CHOLESTEROL IN CORONARY HEART DISEASE IN THE KINGDOM OF SAUDI ARABIA

Cardiovascular disease (CVD) accounted for 42% of deaths in the Kingdom of Saudi Arabia (KSA) in 2011. Patients with CVD, especially coronary heart disease (CHD), are at high risk of CV events; low-density lipoprotein-cholesterol (LDL-C) levels being the major risk factor. Few patients remain uncontrolled with statins monotherapy to achieve desired LDL-C levels. Recently, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) such as alirocumab and evolocumab, were approved as adjunct to statin therapy for the management of patients with CHD having uncontrolled LDL-C levels. This study estimated the budgetary impact of adopting PCSK9i as an add-on treatment to statin therapy for the management of uncontrolled LDL-C patients with CHD in the Ministry of Health (MoH) of KSA. A budget impact (BI) model was developed to assess two scenarios - “with PCSK9i” and “without PCSK9i” as add-on therapy to statins over a five-year time horizon. The key model inputs included CVD patients eligible for PCSK9i treated at MoH facilities, statin market shares, CV event rates and costs, and drug costs. The CV event rate reduction was based on the rate ratio obtained from the ODEYSSEY outcomes study. Model inputs were retrieved from literature and validated by key-experts through face-to-face interviews. The BI analysis demonstrated that the “with PCSK9i” scenario resulted in an increase of 6.1% (SAR 91.16 million) in the budget of Hypercholesterolemia management compared to the “without PCSK9i” scenario. The overall increase was partially offset by SAR 13.5 million reduction in CV events from 0.3% (year 1) to 1.5% (year 5). Introducing PCSK9i as an add-on therapy for the management of CHD patients with uncontrolled LDL-C would reduce CV events and could likely be associated with a steady increase in the MoH budget in KSA triggering restriction to certain patient pool and innovative entry agreement.

Lipid treatment and goal attainment characteristics among persons with atherosclerotic cardiovascular disease in the United States

ObjectiveNational estimates of atherosclerotic cardiovascular disease (ASCVD) in the United States (US) are scarce, especially for patients grouped by cardiovascular risk, lipid-lowering therapy use, and low-density lipoprotein cholesterol (LDL-C) levels. The objective of this study was to estimate the size of the ASCVD population, including the subgroup at very high risk for recurrent events as defined by the 2018 Multi-Society Cholesterol Guidelines. MethodsPatient-level data from the Truven MarketScan Research Database were used and extrapolated to approximate national figures based on known national demographic and ASCVD prevalence numbers. Demographic and clinical characteristics, including LDL-C levels and lipid-lowering therapy use, were captured. ResultsThe extrapolated prevalence of ASCVD in 2014 was 18.3 million, of whom 690,524 had an acute coronary syndrome event in the past year. An estimated 41.4% of patients with ASCVD had diabetes, 44.9% had polyvascular disease, and 23.8% had multiple cardiovascular events. A third of those with ASCVD were estimated to be at very high risk for subsequent events per the 2018 Multi-Society Cholesterol Guidelines. Of those with ASCVD, 74.2% were estimated to have an LDL-C level of ≥70 ​md/dL, and more than half of these patients were neither on statins nor ezetimibe. Only 9.2% of patients with ASCVD and LDL-C ≥70 ​mg/dL were on a high-intensity statin. ConclusionsThe underutilization of lipid-lowering therapies in general, and in particular the relatively low usage of high-intensity statins among patients with uncontrolled LDL-C (including those at very high risk), suggests that eligible patients for proprotein convertase subtilisin/kexin type 9 inhibitor therapy may not be as numerous as previously estimated.

P1223Attributable risk proportion of uncontrolled low-density lipoprotein cholesterol in recurrent acute coronary syndromes

Abstract Background Coronary heart disease is chronic condition that usually has recurrent events. Risk factors for incident coronary heart disease are well known conditions related to recurrences have not been clearly outlined. Attributable risk proportion (ARP) refers to the proportion of incident cases in subjects exposed to risk factors that are attributable to that risk factor so we analysed ARP in wide cohort of patients admitted for an acute coronary syndrome (ACS). Methods Cross-sectional analysis of all patients admitted in two hospitals between January 2006 and December 2016. ARP was calculated by the equation: prevalence in exposed – (prevalence in exposed/odds ratio). LDL uncontrolled was codified as &gt;70 mg/dl in patients with previous cardiovascular disease; &gt;100 mg/dl in patients with diabetes without previous cardiovascular disease or; &gt;155 mg/dl in patients without cardiovascular disease. Results We included 7,518 patients, mean age 66.9 (12.9) years, 72.5% males, median GRACE score 143.2 (40.3) and 35.3% STEMI. Previous coronary heart disease total was present in 2,032 (23.2%) patients and they had statistically higher mean age (70.6±11.11 vs. 65.8±13.3), prevalence of diabetes (37.9% vs. 25.3%) and hypertension (72.9% vs. 53.3%) and lower smoking habit (15.5% vs. 30.9%). LDLc was lower in patients with previous coronary heart disease (90.3±33.8 vs. 111.7±38.1; p&lt;0.01), as well as HDLc (33.5±14.29 vs. 35.9±35.5; p&lt;0.01) and haemoglobin (13.5±3.7 vs. 14.0±2.4; p&lt;0.01). Uncontrolled LDLc was present in 83.4% of the patients with previous coronary heart disease, in contrast to the 28.7% of patients without previous coronary heart disease; this resulted in an ARP of 13.8%. The ARP for diabetes and hypertension were 1.6% and 1.4%, respectively. Conclusions The proportion of attributable risk of uncontrolled LDL on recurrent ACS is 13.8% and, therefore, 1 out of every 7 recurrent ACS could be prevented by an accurate LDLc control.

Pharmacokinetics and exploratory efficacy biomarkers of bococizumab, an anti-PCSK9 monoclonal antibody, in hypercholesterolemic Japanese subjects .

Objective: Bococizumab, a monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, has been shown to reduce low-density lipoprotein cholesterol (LDL-C). Here, we describe the pharmacokinetics and pharmacodynamics of bococizumab and its effect on lipoprotein particle composition and other biomarkers, based on a double-blind, placebo-controlled, randomized, dose-ranging study. Materials and methods: The study consisted of two populations: Japanese subjects with uncontrolled LDL-C (LDL-C ≥ 100 mg/dL) despite treatment with atorvastatin (n = 121) and Japanese subjects naïve to lipid-lowering agents with LDL-C ≥ 130 mg/dL (n = 97). Subjects were randomized to receive either bococizumab 50, 100, or 150 mg or placebo, every 2 weeks. One arm of subjects in the atorvastatin-treated population received ezetimibe 10 mg instead of bococizumab. Results: In both populations, bococizumab exposure increased with increasing dose, and subjects with lower body weights tended to have higher exposures. Bococizumab treatment was associated with a dose-dependent reduction in LDL particles and a small increase in total high-density lipoprotein (HDL) particles. Significant reductions in lipoprotein-associated phospholipase A2 (Lp-PLA2) were observed for bococizumab-treated subjects but not for subjects treated with placebo or ezetimibe. Conclusion: Increased bococizumab dosage resulted in increased exposure. Levels of LDL and HDL particles and biomarkers such as Lp-PLA2 were also altered with bococizumab treatment. (ClinicalTrials.gov identifier: NCT02055976).