Median Low-density Lipoprotein Cholesterol Level Research Articles

Prescription of lipid-lowering therapy, LDLc control, and risk of MACE in patients after ST-elevation myocardial infarction in Mexico

Abstract Funding Acknowledgements None. Background/Introduction Optimal control of low-density lipoprotein cholesterol (LDLc) has been demonstrated to reduce cardiovascular event rates after ST-elevation myocardial infarction (STEMI). However, real-world data shows that a low proportion of patients achieve LDLc targets. Furthermore, the association of LDLc levels and major cardiovascular adverse events (MACE) in post-STEMI patients is limited in developing countries. Purpose In this study, we aimed to assess the prescription patterns of lipid-lowering therapies, LDLc control, and their impact on the risk of MACE after STEMI in Mexico. Methods We conducted a prospective observational study of patients with STEMI. LDLc levels and prescriptions of lipid-lowering therapy were assessed during the first scheduled visit following STEMI hospital discharge. LDLc control was determined in accordance with the 2023 European Society of Cardiology Acute Coronary Syndrome Guidelines, which recommend achieving LDLc levels below 55 mg/dL for secondary prevention. Patients were categorized as controlled (if LDLc <55 mg/dL) and not controlled (if LDLc >55 mg/dL) and were followed for a median of 4.5 years to evaluate the rate of MACE, including cardiovascular death, cardiogenic shock, recurrent MI, and heart failure. Results We included 447 patients with a mean age of 57.87 (± 10.5 years), predominantly male (84.5%). Hypertension (43.8%), smoking (41.1%), type 2 diabetes mellitus (33.5%), obesity (26.6%), and dyslipidemia (21.4%) were highly prevalent. The median LDLc level in the total population was 65.4 mg/dL (IQR 49.2- 87.7). Among these, 34% (152) were considered controlled, while 66% (295) were not. Baseline clinical characteristics did not significantly differ among the groups. Prescription of high-intensity statins reached 94.7%, and ezetimibe and PCSK-9i were used in 1.8% and 0.4% of cases, respectively. We observed no statistically significant difference (Hazard ratio: 1.03, 95% confidence interval 0.74-1.73) in the rate of MACE based on LDLc control (Fig.1). The risk of MACE was also not different based on the use of high-intensity statins. Conclusions In this real-world study of patients post-STEMI, LDLc control was achieved in just one-third of the population. While the prescription of high-intensity statins was high, combination therapy was low. We did not observe a statistically significant association with an increased long-term risk of MACE; however, we noted a higher rate of events compared with other series.

Long-term treatment persistence and maintained reduction of LDL-cholesterol levels with evolocumab over 30 months: Results from the Spanish cohort of the European prospective HEYMANS study

AimsLimited data exist on low-density lipoprotein-cholesterol (LDL-C) level variability or long-term persistence with the monoclonal antibody evolocumab in routine clinical practice. HEYMANS (NCT02770131) is the first multi-country, multicenter, observational study of European patients initiating evolocumab as part of their routine clinical management, based on local reimbursement criteria (overall data recently published). The aim of this analysis is to describe clinical characteristics, baseline and changes in LDL-C levels, treatment patterns and persistence to evolocumab over 30 months in the Spanish cohort using data from the HEYMANS Registry. MethodsHEYMANS was a prospective study of adult patients (≥18 years) who received at least one dose of evolocumab. A total of 1951 patients were enrolled from 12 countries and were followed up for 30 months after evolocumab initiation. Data were collected for 6 months before evolocumab initiation and up to 30 months thereafter. The Spanish cohort included patients who started evolocumab in routine clinical practice from March 2016 to September 2019. Demographic and clinical characteristics, lipid-lowering therapies (LLT), and lipid levels were collected. ResultsIn total, 201 patients were included in the Spanish cohort. Median follow-up (Q1–Q3) was 30.0 (12–30) months. A total of 61.7% of patients were men and the mean (standard deviation) age was 59.5 (10.8) years. Most patients (68.7%) had experienced a prior cardiovascular event, 45.3% had coronary artery disease or stable angina, and 60.2% had a diagnosis of familial hypercholesterolemia. Overall, 57.7% of patients were receiving treatment with statins, most of them with high-intensity statins (85.3%); 45.8% of patients were intolerant to statins, and 26.4% of patients did not receive any LLT. At baseline, median (Q1–Q3) LDL-C levels were 151 (123–197) mg/dL. After 3 months of treatment, baseline LDL-C decreased by 66% to a median of 50 (30–83) mg/dL and these levels were maintained over time, with a median LDL-C of 55 (40–99) mg/dL at 30 months. At months 10–12 of treatment, LDL-C levels<55mg/dL were achieved by 56.3% of patients. LDL-C levels<70mg/dL were achieved by 70.1% of patients, and a lowering of LDL-C levels ≥50% was achieved by 76.8% of patients. The percentage of patients on evolocumab treatment was 95% at 12 months and 93% at 30 months. ConclusionsIn the Spanish cohort in routine clinical practice, evolocumab therapy provided a reduction in LDL-C levels consistent with that reported in previous clinical trials, which was sustained during 30 months of follow-up. Treatment with evolocumab was started at LDL-C levels 50% higher than those recommended by The Spanish Society of Arteriosclerosis and the Therapeutic Positioning Report. The probability of achieving the 2019 ESC/EAS LDL-C goals would improve with combination therapy and also with a lower LDL-C threshold when starting evolocumab. Persistence to evolocumab remained high during follow-up, with a very low percentage of discontinuation (5% at 12 months; 7% at 30 months).

Lipid lowering effects and safety of evolocumab in Chinese patients at very high cardiovascular risk: a single-center study.

Lipid lowering effects and safety of evolocumab in Chinese patients at very high cardiovascular risk: a single-center study.

Elevated low-density lipoprotein cholesterol: An inverse marker of morbidity and mortality in patients with myocardial infarction.

The incidence of atherosclerotic cardiovascular disease increases with levels of low-density lipoprotein cholesterol (LDL-C). Yet, a paradox may exist where lower LDL-C levels at myocardial infarction (MI) are associated with poorer prognoses. To assess the association between LDL-C levels at MI with risk factor burden and cause-specific outcomes. Statin-naive patients hospitalized for a first MI and registered in SWEDEHEART were included. Data were linked to Swedish registers. Primary outcomes were all-cause mortality and nonfatal MI. Associations between LDL-C and outcomes were assessed using adjusted proportional hazards models. Among 63,168 patients (median age, 66 years), the median LDL-C level was 3.0mmol/L (interquartile range 2.4-3.6). Patient age and comorbidities increased as LDL-C decreased. During a median follow-up of 4.5 years, 10,236 patients died, and 4973 had nonfatal MI. Patients with the highest LDL-C had a lower risk of mortality (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.71-0.80). The risk of hospitalization for pneumonia, hip fracture, chronic obstructive pulmonary disease, and new cancer diagnosis was lower with higher LDL-C (HR range, 0.40-0.81). Patients with the highest LDL-C had a greater risk of recurrent MI (HR 1.16; 95% CI 1.07-1.26). Patients with the highest LDL-C levels at MI had the lowest incidence of mortality and morbidity. This seems to reflect lower age at MI, less underlying morbidities, paired with the modifiability of LDL-C. However, supporting the causal association between LDL-C and ischemic heart disease, elevated LDL-C was simultaneously associated with an increased risk of nonfatal MI.

Long-term treatment persistence and maintained reduction of LDL-cholesterol levels with evolocumab over 30 months: Results from the Spanish cohort of the European prospective HEYMANS study

AimsLimited data exist on low-density lipoprotein-cholesterol (LDL-C) level variability or long-term persistence with the monoclonal antibody evolocumab in routine clinical practice. HEYMANS (NCT02770131) is the first multi-country, multicenter, observational study of European patients initiating evolocumab as part of their routine clinical management, based on local reimbursement criteria (overall data recently published). The aim of this analysis is to describe clinical characteristics, baseline and changes in LDL-C levels, treatment patterns and persistence to evolocumab over 30 months in the Spanish cohort using data from the HEYMANS Registry. MethodsHEYMANS was a prospective study of adult patients (≥18 years) who received at least one dose of evolocumab. A total of 1951 patients were enrolled from 12 countries and were followed up for 30 months after evolocumab initiation. Data were collected for 6 months before evolocumab initiation and up to 30 months thereafter. The Spanish cohort included patients who started evolocumab in routine clinical practice from March 2016 to September 2019. Demographic and clinical characteristics, lipid-lowering therapies (LLT), and lipid levels were collected. ResultsIn total, 201 patients were included in the Spanish cohort. Median follow-up (Q1–Q3) was 30.0 (12–30) months. A total of 61.7% of patients were men and the mean (standard deviation) age was 59.5 (10.8) years. Most patients (68.7%) had experienced a prior cardiovascular event, 45.3% had coronary artery disease or stable angina, and 60.2% had a diagnosis of familial hypercholesterolemia. Overall, 57.7% of patients were receiving treatment with statins, most of them with high-intensity statins (85.3%); 45.8% of patients were intolerant to statins, and 26.4% of patients did not receive any LLT. At baseline, median (Q1–Q3) LDL-C levels were 151 (123–197) mg/dL. After 3 months of treatment, baseline LDL-C decreased by 66% to a median of 50 (30–83) mg/dL and these levels were maintained over time, with a median LDL-C of 55 (40–99) mg/dL at 30 months. At months 10–12 of treatment, LDL-C levels<55mg/dL were achieved by 56.3% of patients. LDL-C levels<70mg/dL were achieved by 70.1% of patients, and a lowering of LDL-C levels ≥50% was achieved by 76.8% of patients. The percentage of patients on evolocumab treatment was 95% at 12 months and 93% at 30 months. ConclusionsIn the Spanish cohort in routine clinical practice, evolocumab therapy provided a reduction in LDL-C levels consistent with that reported in previous clinical trials, which was sustained during 30 months of follow-up. Treatment with evolocumab was started at LDL-C levels 50% higher than those recommended by The Spanish Society of Arteriosclerosis and the Therapeutic Positioning Report. The probability of achieving the 2019 ESC/EAS LDL-C goals would improve with combination therapy and also with a lower LDL-C threshold when starting evolocumab. Persistence to evolocumab remained high during follow-up, with a very low percentage of discontinuation (5% at 12 months; 7% at 30 months).

Persistence with long-term PCSK9 inhibitor treatment and its effectiveness in familial hypercholesterolaemia: data from the SAFEHEART study.

Most heterozygous familial hypercholesterolaemia (FH) patients require intensive lipid-lowering therapy (LLT) including PCSK9 inhibitors (PCSK9is) to reach current low-density lipoprotein cholesterol (LDL-C) goals. Persistence with chronic treatment is important to reduce the burden of atherosclerotic cardiovascular disease. We analysed persistence, efficacy, and impact on quality of life (QoL) of PCSK9i in FH patients in clinical practice setting. Spanish Familial Hypercholesterolaemia Cohort Study (SAFEHEART) is an open, prospective study in genetically defined FH patients in Spain. Patients ≥18 years of age (n = 696, 46% females) on stable LLT treated with PCSK9i were analysed. Median LDL-C at starting PCSK9i was 145 mg/dL [interquartile range (IQR), 123-177], 3.8 mmol/L (IQR 3.2-4.6). After a median follow up of 3.7 years (IQR 2.3-4.8), 27 patients (4%) discontinued PCSK9i treatment: 5 temporarily (0.7%) and 22 permanently (3.2%). Persistence with PCSK9i was 96.1% in the whole period. Median LDL-C levels and % LDL-C reduction attained after 1 year of treatment and in the last follow-up visit were 63 mg/dL (IQR 43-88), 1.6 mmol/L (IQR 1.1-2.23); 61 mg/dL (IQR 44-82), 1.6 mmol/L (IQR 1.1-2.1); 57.6% (IQR 39.5-69); and 58% (IQR 44-68), respectively. 2016 and 2019 ESC/EAS LDL-C goals were attained by 77 and 48% of patients, respectively, at the last follow-up visit (P < 0.001). Mean QoL score increased slightly in the first year and remained stable. Long-term persistence with PCSK9i in FH patients is very high, with a good QoL. Effectiveness in LDL-C reduction and LDL-C goal achievement dramatically improved with PCSK9i in this high-risk population in clinical practice setting. ClinicalTrials.gov number NCT02693548.

Hypercholesterolemia diagnosis, treatment patterns and target achievement in patients with acute coronary syndromes in Germany.

Patients who experience an acute coronary syndrome (ACS) are at high risk of further cardiovascular events. Long-term treatment of cardiovascular risk factors, such as hyperlipidemia, is critical to prevent progression of coronary heart disease. However, many patients do not reach recommended target levels for low-density lipoprotein (LDL) cholesterol, despite receiving lipid-lowering therapy. To obtain an insight into the current treatment situation for very high-risk patients after an initial ACS in Germany. The multicenter HYDRA-ACS registry study was initiated to document the clinical characteristics of very high-risk patients with ACS and hyperlipidemia in clinical practice. In addition, lipid profiles, lipid-lowering therapy, and lipid target achievement during treatment were documented over 1 year. 353 patients who were documented had a mean age of 57.3years, mean body mass index was 28.6kg/m2, and 73.4% were male; 52.4% had a family history of myocardial infarction (MI) and 32.6% a family history of coronary heart disease (CHD). Patients' medical histories commonly included CHD (32.9%), percutaneous coronary intervention (PCI; 25.5%), and previous ACS (23.0%). Common comorbidities included hypertension (68.6%), diabetes (17.3%), heart failure (16.7%), and stable angina pectoris (15.9%). The proportion of patients receiving lipid-lowering therapy increased from 65.7% at baseline to 100% at the 12-month follow-up (p < 0.0001). Substantial increases in use were seen for statins (85.0% vs. 36.5%, p = 0.0002) and cholesterol resorption inhibitors (32.9% vs. 8.6%, p = 0.0003). Use of combination therapy increased. The proportion of patients undertaking physical exercise increased (p < 0.0001), as did consumption of fruit and vegetables (p = 0.0222) and fish (p = 0.0162), while alcohol consumption decreased (p = 0.0019). Median LDL cholesterol level decreased significantly from baseline (87 vs. 166mg/dL, p < 0.0001), and the proportion of patients with a level < 70mg/dL increased (50.0% vs. 5.7%, p < 0.0001). Median HDL cholesterol increased (47 vs. 45mg/dL, p = 0.0235) and median triglyceride level decreased (119 vs. 148mg/dL, p = 0.0080). The proportion of patients receiving antihypertensive drugs and platelet aggregation inhibitors increased. The most frequent cardiovascular events during the 12-month follow-up were PCI (25.9%) and cardiac catheterization without PCI (12.9%); MI occurred in 2.4% of patients; no deaths were reported. This study provides a contemporary picture of the treatment of hyperlipidemia after ACS in patients in Germany. Despite treatment with lipid-lowering therapy, many patients did not achieve recommended lipid targets by 12months after an ACS event.

Evolocumab enables rapid LDL-C reduction and inflammatory modulation during in-hospital stage of acute coronary syndrome: A pilot study on Chinese patients.

Background and aimsProprotein convertase subtilisin/kexin type 9 (PCSK9) has long been considered a key regulator in lipid metabolism. Its role as a potential player in immune response has recently earned much attention. However, the effects of evolocumab, an approved PCSK9 monoclonal antibody, on lipid reduction and inflammation regulation in Chinese patients with acute coronary syndrome (ACS) during their in-hospital stage after an index event are not well known.MethodsWe conducted a case-crossover pilot study (http://www.clinicaltrials.gov/, NCT04730648) involving 31 patients hospitalized for ACS with elevated low-density lipoprotein cholesterol (LDL-C) level (≥70 mg/dL despite high-intensity statin) and 8 age- and gender-matched patients without coronary heart disease (CHD) as the baseline control. The patients with ACS received one dose of subcutaneous evolocumab (140 mg) on top of 10 mg/day rosuvastatin during hospitalization. Blood samples at baseline and 72 h post-evolocumab administration were collected for lipid and cytokine assessments.ResultsThe patients without CHD shared similar risk factors and LDL-C levels with the patients with ACS but exhibited a more activated inflammatory status. After single-dose in-hospital evolocumab, the median LDL-C level of patients with ACS decreased from 109.0 to 41.4 mg/dL as early as 72 h, accompanied with reductions in other atherogenic lipids. Systemic inflammatory pattern was also altered, rendering a decrease in pro-inflammatory and anti-inflammatory cytokines.ConclusionIn this case-crossover study of the effect of PCSK9 antibody among Chinese patients, evolocumab on top of high-intensity statin during hospitalization led to a remarkable and rapid reduction in atherogenic lipids and an alteration in inflammatory status at early-stage post-ACS.

Attainment of low-density lipoprotein cholesterol goals in statin treated patients: Real-world evidence from Australia.

Little is known about the attainment of low-density lipoprotein cholesterol (LDL-C) targets in patients treated with statins in Australian primary healthcare setting that are at increased risk of cardiovascular disease. A retrospective cohort study was conducted using data from electronic medical records of patients treated by general practitioners across Australia. LDL-C target attainment was defined as LDL-C levels ≤ 2 mmol/L for all risk groups, in line with Australian guidelines. Multivariable logistic regression was used to identify the factors associated with LDL-C target attainment. Overall, 61,407 patients were included in the analysis. The mean age was 65 years (± standard deviation [SD] 12.1); 52.0% were males.. Overall, the median LDL-C level was 2.3 mmol/L (IQR = 1.8 - 2.8) and 36.0% of the study population met therapeutic targets. Increased likelihood to achieve LDL-C targets was observed in patients diagnosed with type 2 diabetes (OR 2.07, 95% CI 1.92 - 2.24), stroke (OR = 1.58, 95% CI 1.39 - 1.79, P < 0.001) or chronic heart disease (OR = 1.67, 95% CI 1.55 - 1.81, P < 0.001). Patients diagnosed with dyslipidemia (OR = 0.59, 95% CI 0.55 - 0.64, P < 0.001), hypertension (OR = 0.91, 95% CI 0.83 - 1.00, P < 0.05) and current smokers (OR = 0.71, 95% CI 0.71 - 1.00, P < 0.05), were less likely to attain LDL-C targets, regardless of the type, intensity and length of use of the prescribed statin. Longer duration and higher intensity statin were associated with more patients achieving targeted LDL-C goal, however nearly two thirds of Australians still failed to achieve targeted outcome even after 24 months of statin therapy.

Baseline low-density lipoprotein cholesterol predicts the benefit of adding ezetimibe on statin in statin-na\xefve acute coronary syndrome

We aimed to evaluate the effect of baseline low-density lipoprotein cholesterol (LDL-C) on the outcomes of patients with the acute coronary syndrome (ACS) receiving pitavastatin monotherapy or the combination of pitavastatin + ezetimibe. In the HIJ-PROPER study, 1734 ACS patients with dyslipidemia were randomly assigned to receive pitavastatin or pitavastatin + ezetimibe therapy. Statin-naïve participants (n = 1429) were divided into two groups based on the median LDL-C level (131 mg/dL) at enrollment. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, and ischemia-driven coronary revascularization. The median follow-up was 3.2 years. In the < 131 mg/dL group (n = 686), LDL-C changes were − 34.0% and − 49.8% in the pitavastatin monotherapy and pitavastatin + ezetimibe-treated groups (P < 0.0001), respectively; in the ≥ 131 mg/dL group (n = 743), LDL-C changes were − 42.9% and − 56.4% (P < 0.0001, respectively. Kaplan–Meier analyses revealed that the primary endpoint was not significantly different between the treatment groups for the < 131 mg/dL group, however, it was significantly lower in patients treated with pitavastatin + ezetimibe in the ≥ 131 mg/dL group (Hazard ratio = 0.72, 95% confidence interval = 0.56–0.91, P = 0.007, P value for interaction = 0.012). Statin-naïve ACS patients with baseline LDL-C < 131 mg/dL did not clinically benefit from pitavastatin + ezetimibe, while patients with baseline LDL-C ≥ 131 mg/dL treated with pitavastatin + ezetimibe showed better clinical results than those treated with pitavastatin monotherapy.Clinical Trial Registration: Original HIJ PROPER study; URL: http://www.umin.ac.jp/ctr. Unique Identifier; UMIN000002742, registered as an International Standard Randomized Controlled Trial.

Efficacy and safety for the achievement of guideline-recommended lower low-density lipoprotein cholesterol levels: a systematic review and meta-analysis.

The 2018 American Heart Association/American College of Cardiology/Multi-Society Cholesterol Guidelines recommended the addition of non-statins to statin therapy for high-risk secondary prevention patients above a low-density lipoprotein cholesterol (LDL-C) threshold of ≥70 mg/dL (1.8 mmol/L). We compared effectiveness and safety of treatment to achieve lower (<70) vs. higher (≥70 mg/dL) LDL-C among patients receiving intensive lipid-lowering therapy (statins alone or plus ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors). Eleven randomized controlled trials (130 070 patients), comparing intensive vs. less-intensive lipid-lowering therapy, with follow-up ≥6 months and sample size ≥1000 patients were selected. Meta-analysis was reported as random effects risk ratios (RRs) [95% confidence intervals] and absolute risk differences (ARDs) as incident cases per 1000 person-years. The median LDL-C levels achieved in lower LDL-C vs. higher LDL-C groups were 62 and 103 mg/dL, respectively. At median follow-up of 2 years, the lower LDL-C vs. higher LDL-C group was associated with significant reduction in all-cause mortality [ARD -1.56; RR 0.94 (0.89-1.00)], cardiovascular mortality [ARD -1.49; RR 0.90 (0.81-1.00)], and reduced risk of myocardial infarction, cerebrovascular events, revascularization, and major adverse cardiovascular events (MACE). These benefits were achieved without increasing the risk of incident cancer, diabetes mellitus, or haemorrhagic stroke. All-cause mortality benefit in lower LDL-C group was limited to statin therapy and those with higher baseline LDL-C (≥100 mg/dL). However, the RR reduction in ischaemic and safety endpoints was independent of baseline LDL-C or drug therapy. This meta-analysis showed that treatment to achieve LDL-C levels below 70 mg/dL using intensive lipid-lowering therapy can safely reduce the risk of mortality and MACE.

Efficacy and Safety for the Achievement of Guideline-Recommended Lower Low-Density Lipoprotein Cholesterol Levels: A Systematic Review and Meta-Analysis

AIM The 2018 American Heart Association/American College of Cardiology/Multi-Society Cholesterol Guidelines recommended the addition of non-statins to statin therapy for high-risk secondary prevention patients above a low-density lipoprotein cholesterol (LDL-C) threshold of ≥70 mg/dL (1.8 mmol/L). We compared effectiveness and safety of treatment to achieve lower (<70) vs. higher (≥70 mg/dL) LDL-C among patients receiving intensive lipid-lowering therapy (statins alone or plus ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors). METHODS AND RESULTS Eleven randomized controlled trials (130 070 patients), comparing intensive vs. less-intensive lipid-lowering therapy, with follow-up ≥6 months and sample size ≥1000 patients were selected. Meta-analysis was reported as random effects risk ratios (RRs) [95% confidence intervals] and absolute risk differences (ARDs) as incident cases per 1000 person-years. The median LDL-C levels achieved in lower LDL-C vs. higher LDL-C groups were 62 and 103 mg/dL, respectively. At median follow-up of 2 years, the lower LDL-C vs. higher LDL-C group was associated with significant reduction in all-cause mortality [ARD -1.56; RR 0.94 (0.89-1.00)], cardiovascular mortality [ARD -1.49; RR 0.90 (0.81-1.00)], and reduced risk of myocardial infarction, cerebrovascular events, revascularization, and major adverse cardiovascular events (MACE). These benefits were achieved without increasing the risk of incident cancer, diabetes mellitus, or haemorrhagic stroke. All-cause mortality benefit in lower LDL-C group was limited to statin therapy and those with higher baseline LDL-C (≥100 mg/dL). However, the RR reduction in ischaemic and safety endpoints was independent of baseline LDL-C or drug therapy. CONCLUSION This meta-analysis showed that treatment to achieve LDL-C levels below 70 mg/dL using intensive lipid-lowering therapy can safely reduce the risk of mortality and MACE.

Lipoprotein Apheresis and Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients With Heterozygous Familial Hypercholesterolemia: A One Center Study.

We evaluated the lipid-lowering (LL) effect of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with heterozygous familial hypercholesterolemia (HeFH) treated with LL-drugs and lipoprotein apheresis (LA). The PCSK9i treatment (evolocumab 420 mg/4 weeks, alirocumab 150 mg/2 weeks, or alirocumab 75 mg/2 weeks: 9, 6, and 2 patients, respectively) was initiated in patients with HeFH (n = 17; aged 35-69 years, 10 men, previously treated with statins + ezetimibe ± colesevelam and LA sessions for 2-12 years). A lipid profile was obtained before and immediately after the LA session and before, 1 and 2 months after switching to PCSK9i treatment. The duration of PCSK9i therapy ranged from 3 to 18 months. Median total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) levels before LA were 268, 198, 46, and 126 mg/dL, respectively, and decreased (at the end of the LA session) to 117, 50, 40, and 51 mg/dL, respectively (P < .001 for TC and P = .001 for all other comparisons). The median time-averaged LDL-C levels following LA were 155 (121, 176; median [25th, 75th percentile]) mg/dL. Median TC, LDL-C, and TG levels before PCSK9i therapy were 269, 190, and 127 mg/dL and decreased to 152, 100, and 95 mg/dL, respectively (P = .002, P < .002, and P < .03, respectively). Steady LDL-C levels with PCSK9i treatment were significantly lower compared with time-averaged LDL-C levels following LA (median value: 100 vs 155 mg/dL; P = .008). With PCSK9i, from 13 patients with CHD, 6 (46.1%) patients achieved LDL-C <70 mg/dL, and 2 patients (15.4%) achieved LDL-C <100 mg/dL. Lipoprotein apheresis was discontinued in all patients except for 2 who continued once monthly. PCSK9i can reduce LDL-C more consistently over time compared with a transient decrease following LA in HeFH patients. PCSK9i therapy may reduce the frequency of LA. Larger trials are required to establish the clinical implications of PCSK9i in patients previously on LA.

Management of Hyperlipidemia in Very High and Extreme Risk Patients in Croatia: an observational study of treatment patterns and lipid control.

SUMMARYOur observational study evaluated current management of elevated low-density lipoprotein cholesterol (LDL-C) in adult secondary prevention patients (all very high risk (VHR) by European guidelines) attending specialist clinics across Croatia. Data were collected retrospectively from patient records for the preceding 12 months. The subset judged to be at extreme risk (ER; American Association of Clinical Endocrinologists (AACE) criteria; n=48) were compared with the remaining patients (VHR group; n=41). All patients were receiving statins (75.6% VHR/81.3% ER at high-intensity), with only a minority receiving concomitant lipid-lowering treatment (7.3% VHR/16.7% ER). Median (Q1, Q3) LDL-C levels at the last visit were 1.9 (1.6, 2.4) mmol/L for VHR and 2.1 (1.5, 3.1) mmol/L for ER, with only 41.5% (95% CI 26.3-57.9) of VHR patients and 27.1% (15.3-41.9) of ER patients attaining their LDL-C targets (<1.8 mmol/L and <1.42 mmol/L, respectively). Thus, we found that a substantial proportion of VHR and ER secondary prevention patients being treated across Croatia had LDL-C levels exceeding the targets recommended in the European and newer AACE guidelines, but not all were receiving high-intensity statins. Identification of ER patients and their lipid patterns may help optimize usage of high-intensity statin treatment, alone or along with newer treatments, for better control of elevated LDL-C.

Lowering Targeted Atherogenic Lipoprotein Cholesterol Goals for Patients at "Extreme" ASCVD Risk.

To review randomized interventional clinical and imaging trials that support lower targeted atherogenic lipoprotein cholesterol goals in "extreme" and "very high" atherosclerotic cardiovascular disease (ASCVD) risk settings. Major atherosclerotic cardiovascular event (MACE) prevention among the highest risk patients with ASCVD requires aggressive management of global risks, including lowering of the fundamental atherogenic apolipoprotein B-associated lipoprotein cholesterol particles [i.e., triglyceride-rich lipoprotein remnant cholesterol, low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a)]. LDL-C has been the long-time focus of imaging studies and randomized clinical trials (RCTs). The 2004 adult treatment panel (ATP-III) update recognized that the long-standing targeted LDL-C goal of < 100mg/dL potentially fostered substantial undertreatment of the very highest coronary heart disease (CHD) risk individuals and was lowered to < 70mg/dL as an "optional" goal for "very high" 10-year CHD [CHD death + myocardial infarction (MI)] risk exceeding 20%. This evidence-based guideline change was supported by the observed benefits demonstrated in the high-risk primary and secondary prevention populations in the Heart Protection Study (HPS), the acute coronary syndrome (ACS) population in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 trial (PROVE-IT), and the secondary prevention population in the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) intravascular ultrasound (IVUS) study. Subsequent national and international guidelines maintained a targeted LDL-C goal < 70mg/dL, or a threshold for management of > 70mg/dL for patients with CHD, CHD risk equivalency, or ASCVD. Subgroup or meta-analyses of several RCTs, IVUS imaging studies, and the ACS population in IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) supported the evidence-based 2017 American Association Clinical Endocrinologist (AACE) guideline change establishing a targeted LDL-C goal < 55mg/dL, non-HDL-C < 80mg/dl, and apolipoprotein B (apo B) < 70mg/dL for patients at "Extreme" ASCVD risk, i.e., 10-year 3-point-MACE-composite (CV death, non-fatal MI, or ischemic stroke) risk exceeding 30%. Moreover, with no recognized lower-limit-associated intolerance or safety issues, even more intensive lowering of atherogenic cholesterol levels is supported by the following evidence base: (1) analysis of eight high-intensity statin-based prospective secondary prevention IVUS atheroma volume regression trials; (2) a distribution analysis of on-treatment, ezetimibe and background-statin, of the very low LDL-C levels reached and CVD event risk in the IMPROVE-IT ACS population; (3) the secondary prevention Global Assessment of Pl\aque Regression With a PCSK9 Antibody as Measured by Intravascular Ultrasound (GLAGOV) on background-statin; and (4) the secondary prevention population of Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER). By example, in FOURIER, the population on background-statin at a baseline median 92mg/dL achieved median LDL-C level of 30mg/dL and non-HDL-C to < 65mg/dl, and apo B to < 50mg/dL, and subgroup and post hoc analyses all demonstrated additional ASCVD event reduction benefits as LDL-C was further reduced. The level of ASCVD risk determines the degree, urgency, and persistence in global risk management, including fundamental atherogenic lipoprotein cholesterol particle lowering. "Extreme" risk patients may require extremely low targeted LDL-C, non-HDL-C and apo B goals; such efforts, implied by more recent interventional trials and analyses, are aimed at maximal atheroma plaque regression, stabilization, and MACE event reduction with the aspiration of improved quality lifespan.

A Retrospective Observational Study to Determine Baseline Characteristics and Early Prescribing Patterns for Patients Receiving Alirocumab in UK Clinical Practice.

BackgroundAlirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) and has been previously shown, in the phase III ODYSSEY clinical trial program, to provide significant lowering of low-density lipoprotein cholesterol (LDL-C) and reduction in risk of major adverse cardiovascular events. However, real-world evidence to date is limited.ObjectiveThe primary objective was to describe baseline characteristics, clinical history, and prior lipid-lowering therapy (LLT) use of patients initiated on alirocumab in UK clinical practice following publication of health technology appraisal (HTA) body recommendations. Secondary objectives included description of alirocumab use and lipid parameter outcomes over a 4-month follow-up period.MethodsIn this retrospective, single-arm, observational, multicenter study, data were collected for 150 patients initiated on alirocumab.ResultsMean (standard deviation; SD) age of patients was 61.4 (10.5) years and baseline median (interquartile range; IQR) LDL-C level was 4.8 (4.2–5.8) mmol/l. Alirocumab use occurred predominantly in patients with heterozygous familial hypercholesterolemia (HeFH) (n = 100/150, 66%) and those with statin intolerance (n = 123/150, 82%). Most patients started on alirocumab 75 mg (n = 108/150 [72%]) and 35 (23.3%) were up-titrated to 150 mg. Clinically significant reductions in atherogenic lipid parameters were observed with alirocumab, including LDL-C (median [IQR] change from baseline, − 53.6% [− 62.9 to − 34.9], P < 0.001).ConclusionThis study highlights the unmet need for additional LLT in patients with uncontrolled hyperlipidemia and demonstrates the clinical utility of alirocumab in early real-world practice, where dosing flexibility is an important attribute of this therapeutic option.Electronic supplementary materialThe online version of this article (10.1007/s40801-019-00166-7) contains supplementary material, which is available to authorized users.

P5365Microsomal triglyceride transfer protein inhibitor (lomitapide) efficacy in the treatment of patients with homozygous familial hypercholesterolemia phenotype

Abstract Introduction The majority of patients with homozygous familial hypercholesterolemia (HoFH) phenotype are treated additionally to lipid lowering (LL) drugs (statin + ezetimibe ± colesevelam) with lipoprotein apheresis (LA) sessions. The aim of this study was to evaluate the effect of microsomal triglyceride transfer protein inhibitor (lomitapide) in HoFH patients. Patients and methods In 12 HoFH patients treated with LL drugs ± biweekly LA sessions (9 patients) the 5–40 mg daily of lomitapide was added. Lipid profile [total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglycerides (TG) and high density lipoprotein cholesterol (HDL-C)] before (LL drugs ± LA) and after lomitapide treatment were evaluated. Results The follow-up period of lomitapide treatment for 12 patients was 3–24 months (13.8±7.9). The median baseline LDL-C levels was 1000 mg/dL (339–1150). During LL drug therapy, patients showed a median LDL-C level of 383.5 mg/dL (Range: 214–866 mg/dL) and with LL drugs + Time-averaged levels (CAVG) the median was 288.1 mg/dL (Range: 183.69–716.65 mg/dL). The addition of lomitapide at the average dosage of 21.4 mg/day lowered LDL-C levels by 56.8% comparing to LL drugs alone therapy [mean reduction 262.12, 95% CI (105.53, 418.71), p=0.005] and by 54% [mean reduction −182.89, 95% CI (−342.35, −23.43), p=0.031] comparing to LL drugs + LA (CAVG). The CAVG of LDL-C in LL drugs + LA patients compared with LL drugs + lomitapide was 54% in favour of lomitapide (p=0.031). After lomitapide administration to LL drugs + LA treatment, 78% patients discontinued LA and 2 patients reduced their LA frequency by 50%. During follow-up, 2 patients (16.6%) reported side effects (transient diarrhea, 1 patient had liver transaminase &gt;5× ULN and had to decrease dose of lomitapide). Two patients stopped lomitapide due to diet and alcohol restrictions. Median and ranges of lipid and lipoprotein values before any intervention, after LL drugs, LL drugs plus LA, LL drugs plus LA (CAVG) and LL drugs plus lomitapide Total Cholesterol LDL-C HDL-C Triglycerides Before any intervention 1000 (339–1150) 900 (245–1070) 34.5 (25–50) 125 (87–314) After LL drugs 434 (278–915) 383.5 (214–866) 36 (27–51) 113 (62–198) LL drugs + LA (CAVG) 336.13 (248.57–784.16) 288.07 (183.69–716.65) 42.81 (25.84–46.68) 105.09 (55.79–166.68) LL drugs + Lomitapide 228.5 (118–554) 173.5 (74–515) 37.5 (29–50) 83.5 (23–316) LDL graph Conclusions Treatment with lomitapide in HoFH patients has beneficial effect with constant decrease of LDL-C by 57% compared with classical LL therapy and by 54% compared with classical LL therapy and CAVG and seems to be with good safety profile. Although, in some cases the hybrid (all availably drug treatment and LA) therapy may be needed.

Efficacy and Safety of Further Lowering of Low-Density Lipoprotein Cholesterol in Patients Starting With Very Low Levels

In the Cholesterol Treatment Trialists Collaboration (CTTC), in patients starting with low-density lipoprotein cholesterol (LDL-C) levels of approximately 3.4 mmol/L (131.5 mg/dL), there was a 22% reduction in major vascular events per 1-mmol/L (38.7-mg/dL) lowering of LDL-C. The magnitude of clinical benefit of further LDL-C lowering in patients already with very low LDL-C levels remains debated. To evaluate efficacy and safety of further lowering LDL-C levels in patient populations presenting with median LDL-C levels of 1.8 mmol/L (70 mg/dL) or less. The CTTC was used for statin data. For nonstatin therapy, Medline database was searched (2015-April 2018). Key inclusion criteria were a randomized, double-blind, controlled cardiovascular outcome trial of LDL-C lowering with data in populations starting with LDL-C levels averaging 1.8 mmol/L (70 mg/dL) or less. Two authors independently extracted data into standardized data sheets, and data were analyzed using meta-analysis. The risk ratio (RR) of major vascular events (a composite of coronary heart death, myocardial infarction, ischemic stroke, or coronary revascularization) per 1-mmol/L (38.7-mg/dL) reduction in LDL-C level. In the subgroup of patients from the CTTC meta-analysis of statins with a mean LDL-C in the control arm of 1.7 mmol/L (65.7 mg/dL), 1922 major vascular events occurred and the RR for major vascular events per 1-mmol/L (38.7-mg/dL) reduction in LDL-C was 0.78 (95% CI, 0.65-0.94). For 3 trials of nonstatin LDL-C-lowering therapies added to statins, there were 50 627 patients, the median LDL-C in the control arms ranged from 1.6 mmol/L to 1.8 mmol/L (63 mg/dL to 70 mg/dL), and 9570 major vascular events occurred. Nonstatin therapy lowered LDL-C by 0.3 to 1.2 mmol/L (11 mg/dL to 45 mg/dL), and the RR for major vascular events per 1-mmol/L (38.7-mg/dL) reduction in LDL-C was 0.79 (95% CI, 0.70-0.88). For statins and nonstatins combined, the RR was 0.79 (95% CI, 0.71-0.87; P < .001). Low-density lipoprotein cholesterol lowering was not associated with an increased risk of serious adverse events, myalgias and/or myositis, elevation in the level of aminotransferases, new-onset diabetes, hemorrhagic stroke, or cancer. There is a consistent relative risk reduction in major vascular events per change in LDL-C in patient populations starting as low as a median of 1.6 mmol/L (63 mg/dL) and achieving levels as low as a median of 0.5 mmol/L (21 mg/dL), with no observed offsetting adverse effects. These data suggest further lowering of LDL-C beyond the lowest current targets would further reduce cardiovascular risk.

Lipid management in contemporary community practice: Results from the Provider Assessment of Lipid Management (PALM) Registry

The latest cholesterol guidelines have shifted focus from achieving low-density lipoprotein cholesterol (LDL-C) targets toward statin use and intensity guided by atherosclerotic cardiovascular disease (ASCVD) risk. Statin use and intensity were evaluated in 5,905 statin-eligible primary or secondary prevention patients from 138 PALM Registry practices. Overall, 74.7% of eligible adults were on statins; only 42.4% were on guideline-recommended intensity. Relative to primary prevention patients, ASCVD patients were more likely to be on a statin (83.6% vs 63.4%, P<.0001) and guideline-recommended intensity (47.3% vs 36.0%, P<.0001). Men were more likely than women to be prescribed recommended intensity for primary (odds ratio [OR] 1.87, 95% CI 1.49-2.34) and secondary (OR 1.47, 95% CI 1.26-1.70) prevention. In primary prevention, increasing age, diabetes, obesity, hypertension, and lower 10-year ASCVD risk were associated with increased odds of receiving recommended intensity. Among ASCVD patients, those with coronary artery disease were more likely to be on recommended intensity than cerebrovascular or peripheral vascular disease patients (OR 1.71, 95% CI 1.41-2.09), as were those seen by cardiologists (OR 1.43, 95% CI 1.12-1.83). Median LDL-C levels were highest among patients not on statins (124.0 mg/dL) and slightly higher among those on lower-than-recommended intensity compared with recommended-therapy recipients (88.0 and 84.0 mg/dL, respectively; P≤.0001). In routine contemporary practice, 1 in 4 guideline-eligible patients was not on a statin; less than half were on the recommended statin intensity. Untreated and undertreated patients had significantly higher LDL-C levels than those receiving guideline-directed statin treatment.

The benefit of adding ezetimibe to statin therapy in patients with prior coronary artery bypass graft surgery and acute coronary syndrome in the IMPROVE-IT trial.

To examine the efficacy and safety of ezetimibe added to statin in patients with prior coronary artery bypass graft surgery (CABG) following hospitalization for an acute coronary syndrome (ACS). In the IMPROVE-IT trial, post-ACS patients with mean low density lipoprotein cholesterol (LDL-C) of 93.8 mg/dL at presentation were randomized to simvastatin/ezetimibe or simvastatin/placebo. The primary endpoint was cardiovascular death, major coronary event or stroke, and the median follow-up was 6 years. Efficacy and safety endpoints were examined by prior CABG status. Among 18 134 patients, 1684 (9.3%) had a prior CABG (median age 69 years, 82% male). During the trial, the median time-weighted LDL-C level was 55.0 mg/dL with simvastatin/ezetimibe vs. 69.9 mg/dL with simvastatin/placebo in patients with prior CABG (P < 0.001), and it was 53.6 mg/dL vs. 69.5 mg/dL, respectively, in patients without prior CABG (P < 0.001). The rate of the primary endpoint was higher in patients with vs. without prior CABG [56% vs. 32%, adj. hazard ratio 1.45, 95% confidence interval (CI) 1.33-1.58]. Patients with prior CABG receiving simvastatin/ezetimibe had an 8.8% (95% CI 3.1-14.6%) lower absolute risk over simvastatin/placebo in the primary endpoint, whereas patients without prior CABG had a 1.3% (95% CI 0-2.6%) lower absolute risk (P-interaction = 0.02). There were no between-group significant differences in safety endpoints. The clinical benefit of adding ezetimibe to statin appears to be enhanced in patients with prior CABG, supporting the use of intensive lipid lowering therapy in these high-risk patients following ACS.