Patients Achieving Low-density Lipoprotein Cholesterol Goals Research Articles

Real-World Application of Evolocumab Among Patients with Hyperlipidemia in Korea: A Multicenter Prospective Study.

Elevated low-density lipoprotein cholesterol (LDL-C) is a major residual risk factor among patients with acute coronary syndrome (ACS). In the absence of sufficient real-world evidence, this observational (noninterventional) study investigated the effectiveness and safety of evolocumab in patients with hyperlipidemia treated with evolocumab for ACS in a real-world clinical setting in Korea. Between January 2022 and February 2023, patients from 10hospitals in Korea who initiated evolocumab within 24weeks of an ACS event were enrolled. Data collected at visit1 (evolocumab initiation) included patients' characteristics, comorbidities, and lipid-lowering therapies. LDL-C reduction from visit1 (week0) to visit2 (week8) was assessed. The primary outcome was the proportion of patients who achieved LDL-C < 1.4mmol/L (55mg/dL) at follow-up; the secondary outcome was the proportion who achieved LDL-C < 1.8mmol/L (70mg/dL) at follow-up. In this study, 89 out of 142 enrolled patients were included in the effectiveness analysis. The mean (SD) age of the included patients was 59.3 (12.3) years, with the majority being male (87.6%). Sixty-one patients received statin-ezetimibe combination therapy (68.5%). The median [Q1, Q3] LDL-C level at the start of the study was 2.5 [2.0, 3.0] mmol/L (98 [77, 115] mg/dL), which decreased to 1.3 [0.7, 1.7] mmol/L (49 [29, 67] mg/dL) after 8weeks of evolocumab treatment, resulting in an mean (SD) 50.9 (28.6) % reduction and 1.4 (1.0) mmol/L (55.1 (37.9) mg/dL) absolute reduction. At follow-up, 55.1% and 78.7% of patients achieved LDL-C goals of < 1.4mmol/L (55mg/dL) and < 1.8mmol/L (70mg/dL), respectively. No adverse or serious adverse drug reactions were reported. Evolocumab treatment was associated with significant LDL-C lowering and favorable safety and guideline-recommended LDL-C goal achievement rates among patients with ACS in the real-world clinical practice setting in South Korea.

Lipid goal attainment across baseline socioeconomic and clinical factors comparing an "inclisiran first" implementation strategy and usual care: subgroup analysis of VICTORION-INITIATE

Abstract Background Addressing inequities in cardiovascular care has become a public health priority. Recent results from VICTORION-INITIATE, a pragmatically designed, randomised clinical trial showed the benefit of using inclisiran immediately if patients with atherosclerotic cardiovascular disease (ASCVD) fail to achieve low-density lipoprotein cholesterol (LDL-C) &amp;lt;70 mg/dL (1.8 mmol/L) on maximally tolerated statins. Purpose To evaluate effectiveness and safety of an "inclisiran first" implementation strategy (IF) versus usual care (UC) in subgroups that may be associated with healthcare inequities. Methods VICTORION-INITIATE was conducted at 45 representative clinical settings across 20 states in the USA. Patients with ASCVD randomised 1:1 (stratified by insurance status) received open-label inclisiran 284 mg at Days 0, 90 and 270) plus UC or UC alone (lipid management directed by treating physicians). Treating physicians had access to LDL-C measurements and were encouraged to intensify treatment per lipid guidelines. We compared efficacy and safety endpoints for IF and UC in prespecified subgroups (race, ethnicity, sex, renal function and statin intensity) and by income level (post-hoc analysis). Results The study randomised 450 patients. Baseline demographic and clinical parameters were balanced between study arms (≥65 years of age: IF: 63.1%, UC: 61.3%; non-White: IF: 15.6%, UC: 15.1%; Hispanic: IF: 13.8%, UC: 16.9%; female: IF: 29.8%, UC: 32.0%; income ≤$50,000: IF: 58.7%, UC: 58.2%; estimated glomerular filtration rate ≥30 to &amp;lt;60 mL/min/1.73m2: IF: 20.0%, UC: 17.8%; no statins at baseline: IF: 9.8%; UC: 10.2%). Across all subgroups, more patients achieved LDL-C goals at Day 330 with IF vs UC (Figure 1). Within the UC arm, the proportions of patients achieving LDL-C &amp;lt;70 mg/dL and &amp;lt;55 mg/dL, respectively, were numerically lower for non-White (8.8% and 2.9%) and Hispanic (10.5% and 2.6%) than White (24.6% and 10.2%) and non-Hispanic (24.9% and 10.3%) patients. We did not observe differences in LDL-C goal attainment for these subgroups in patients receiving IF. Compared with UC, IF resulted in greater mean percentage change in other lipids and lipoproteins from baseline to Day 330, irrespective of subgroup (Figure 2). Incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs compared similarly between IF and UC for each subgroup (IF: 35.5−69.2%, UC: 34.2−84.2%, and IF: 3.2−16.9%, UC: 0.0−36.8%, respectively). Conclusions VICTORION-INITIATE enrolled a diverse population reflective of "real-world" US clinical practice. The IF strategy consistently resulted in higher rates of LDL-C goal attainment for all subgroups studied and did not lead to differences in lipid outcomes by race or ethnicity as compared to usual care. No additional safety concerns for the IF strategy were identified.

Recent trends of low-density lipoprotein cholesterol control and lipid-lowering therapy in patients with atherosclerotic cardiovascular disease in Taiwan: 2015–2020

ObjectiveThis study aimd to assess recent trends in the control of low-density lipoprotein cholesterol (LDL-C) and the utilization of lipid-lowering drugs (LLD) among patients with atherosclerotic cardiovascular disease (ASCVD) in Taiwan. MethodsPatients with ASCVD and without a history of hemorrhagic stroke were identified from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. ASCVD patients were stratified into four categories: those who ever had acute coronary syndrome (ACS), those who underwent percutaneous coronary intervention or coronary artery bypass grafting (PCI/CABG) without ACS, those who ever had an ischemic stroke (IS) without ACS or PCI/CABG, and other ASCVD cases. We assessed their latest recorded LDL-C levels for the periods 2015–16, 2017–18, and 2019–20. LLD therapy patterns were presented as monotherapy, dual therapy, or combination therapy of three or more drugs, with statin use classified by intensity. ResultsWe identified 3831 ASCVD patients in 2015–16, 3531 in 2017–18, and 1231 in 2019–20. LLD utilization rose from 58.4% in 2015–16 to 73.2% in 2019–20. The proportions of patients achieving LDL-C goals in 2015–16, 2017–18, and 2019–20 were 21.5%, 25.8%, and 33.3% in the ACS cohort (goal <70 mg/dL); 20.4%, 26.1%, and 39.0% in the PCI/CABG cohort (goal <70 mg/dL); 54.4%, 58.5%, and 58.9% in the IS cohort (goal <100 mg/dL); and 60.0%, 65.5%, and 67.0% in the other ASCVD cohort (goal <100 mg/dL), respectively. Over half of the patients were prescribed moderate-intensity statins. Statin use, age, history of diabetes mellitus, and hypertension were important factors for attaining LDL-C goal in ACS patients. ConclusionDespite improvements in LDL-C management observed over recent years, significant gaps remain in guideline adherence, especially for patients with ACS or PCI/CABG in Taiwan, with over 60% not meeting LDL-C targets. Intensifying efforts to align clinical practice with guidelines are imperative.

An “Inclisiran First” Strategy vs Usual Care in Patients With Atherosclerotic Cardiovascular Disease

BackgroundMost patients with atherosclerotic cardiovascular disease fail to achieve guideline-directed low-density lipoprotein cholesterol (LDL-C) goals. Twice-yearly inclisiran lowers LDL-C by ∼50% when added to statins. ObjectivesThis study evaluated the effectiveness of an “inclisiran first” implementation strategy (adding inclisiran immediately upon failure to reach LDL-C <70 mg/dL despite receiving maximally tolerated statins) vs representative usual care in U.S. patients with atherosclerotic cardiovascular disease. MethodsVICTORION-INITIATE, a prospective, pragmatically designed trial, randomized patients 1:1 to inclisiran (284 mg at days 0, 90, and 270) plus usual care (lipid management at treating physician’s discretion) vs usual care alone. Primary endpoints were percentage change in LDL-C from baseline and statin discontinuation rates. ResultsWe randomized 450 patients (30.9% women, 12.4% Black, 15.3% Hispanic); mean baseline LDL-C was 97.4 mg/dL. The “inclisiran first” strategy led to significantly greater reductions in LDL-C from baseline to day 330 vs usual care (60.0% vs 7.0%; P < 0.001). Statin discontinuation rates with “inclisiran first” (6.0%) were noninferior vs usual care (16.7%). More “inclisiran first” patients achieved LDL-C goals vs usual care (<70 mg/dL: 81.8% vs 22.2%; <55 mg/dL: 71.6% vs 8.9%; P < 0.001). Treatment-emergent adverse event (TEAE) and serious TEAE rates compared similarly between treatment strategies (62.8% vs 53.7% and 11.5% vs 13.4%, respectively). Injection-site TEAEs and TEAEs causing treatment withdrawal occurred more commonly with “inclisiran first” than usual care (10.3% vs 0.0% and 2.6% vs 0.0%, respectively). ConclusionsAn “inclisiran first” implementation strategy led to greater LDL-C lowering compared with usual care without discouraging statin use or raising new safety concerns. (A Randomized, Multicenter, Open-label Trial Comparing the Effectiveness of an “Inclisiran First” Implementation Strategy to Usual Care on LDL Cholesterol [LDL-C] in Patients With Atherosclerotic Cardiovascular Disease and Elevated LDL-C [≥70 mg/dL] Despite Receiving Maximally Tolerated Statin Therapy [VICTORION-INITIATE]; NCT04929249)

Achievement Rates for Low-Density Lipoprotein Cholesterol Goals in Patients at High Risk of Atherosclerotic Cardiovascular Disease in a Real-World Setting in Japan.

The study aimed to investigate low-density lipoprotein cholesterol (LDL-C) goal achievement rates in patients receiving LDL-C-lowering therapy using recent real-world data, following the 2017 revision of the Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases (JAS GL2017). Patients with documented LDL-C test results were extracted from the Medical Data Vision claims database between July 2018 and June 2021 and divided into three groups according to JAS GL2017: primary prevention high risk (Group I, LDL-C goal ＜120 mg/dL), secondary prevention (Group II, LDL-C goal ＜100 mg/dL), and secondary prevention high risk (Group III, LDL-C goal ＜70 mg/dL). The mean LDL-C value was 108.7 mg/dL (n=125,235), 94.4 mg/dL (n=57,910), and 90.6 mg/dL (n=33,850) in Groups I, II, and III, respectively. Intensive statin monotherapy (pitavastatin, rosuvastatin, or atorvastatin) was the most frequently prescribed lipid-lowering treatment (21.6%, 30.8%, and 42.7% in Groups I, II, and III, respectively), followed by ezetimibe (2.5%, 7.1%, and 8.5% in Groups I, II, and III, respectively). LDL-C goals were achieved by 65.5%, 60.6%, and 25.4% of patients overall in Groups I, II, and III, respectively. Achievement rates were 83.9%, 75.3%, and 29.5% in patients prescribed intensive statin monotherapy and 82.3%, 86.4%, and 46.4% in those prescribed statin and ezetimibe combinations in Groups I, II, and III, respectively. In Group III, the proportion of patients with familial hypercholesterolemia prescribed statin and ezetimibe combinations achieving LDL-C goals was low (32.5%). The proportion of patients achieving LDL-C goals for secondary prevention in the high-risk group remains low even with statin and ezetimibe combination therapy.

Real-World Insights into Evolocumab Use in Patients with Hyperlipidemia Across Five Countries: Analysis from the ZERBINI Study.

This study characterizes patients receiving evolocumab in clinical practice and assesses treatment effectiveness, safety and persistence outcomes across five countries. This retrospective and prospective observational study enrolled patients initiated on evolocumab during August 2017 to July 2019 at 49 sites across Canada, Mexico, Colombia, Saudi Arabia and Kuwait. Medical records data were extracted within 6months prior to (baseline) and every 3months for 12months post evolocumab initiation and reported as available. A total of 578 patients were enrolled (40.1% female, median age 60 [interquartile range (IQR) 51-68] years); 83.7% had atherosclerotic cardiovascular disease and/or familial hypercholesterolemia. Median low-density lipoprotein cholesterol (LDL-C) at baseline was 3.4 (IQR 2.7-4.2) mmol/L (131.5 [IQR 104.4-162.4] mg/dL), with 75.6% of patients receiving a statin (59.2% high intensity). Compared to baseline, the median lowest LDL-C was reduced by 70.2% and remained stable over 12months of treatment. Guideline-recommended LDL-C thresholds < 1.8, < 1.4 and < 1.0mmol/L (< 70, < 55 and < 40mg/dL) were achieved by 75.3%, 63.6% and 47.4% of patients. LDL-C outcomes were consistent across high- and very high-risk patients. Background lipid-lowering therapy remained relatively stable. No serious treatment-emergent adverse events were reported, and persistence to evolocumab was 90.2% at 12months. These findings provide real-world evidence that evolocumab use is in accordance with its international guideline-recommended place in dyslipidemia therapy, as well as confirmation of its effectiveness and safety in a heterogeneous population. Evolocumab can address a healthcare gap in the management of dyslipidemia by increasing the proportion of patients achieving LDL-C goals recommended to lower cardiovascular risk.

Real-World Insights Into Evolocumab Use in Patients With Hyperlipidemia: Canadian Analysis From the ZERBINI Study

BackgroundThe 2021 Canadian Cardiovascular Society guidelines recommend proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor therapy in patients with atherosclerotic cardiovascular disease whose low-density lipoprotein cholesterol (LDL-C) concentration remains ≥ 1.8 mmol/L despite maximally tolerated statin therapy. This retrospective and prospective observational study characterizes Canadian patients treated with evolocumab and describes its effectiveness and safety. MethodsBetween August 2017 and July 2019, a total of 131 patients initiated on evolocumab therapy were enrolled at 15 sites in Canada. Data were extracted from medical records every 3 months between 6 months prior to, and for 12 months following evolocumab therapy initiation, until July 6, 2020. Baseline and prospectively collected data are reported as available. ResultsA total of 131 patients were enrolled (59.5% male; mean age [standard deviation (SD)] 64.7 ± 10.6 years), most with a diagnosis of atherosclerotic cardiovascular disease and/or familial hypercholesterolemia (93.4%). Mean (± SD) LDL-C concentration at baseline was 3.7 (± 1.7) mmol/L (n = 119), with 58.0% of patients receiving a statin (36.6% high intensity). Mean (± SD) LDL-C concentration after evolocumab treatment was 1.6 (± 1.0) mmol/L (n = 120), representing a 58.7% decrease from baseline (n = 109). This level remained stable over 12 months. An LDL-C concentration < 1.8 mmol/L was achieved by 77.5% of patients. Persistence was 92%, and no serious treatment-emergent adverse events were reported. ConclusionsThese findings provide real-world evidence of guideline-recommended initiation of evolocumab therapy, as well as confirmation of its effectiveness and safety in a Canadian population. Evolocumab therapy can address a healthcare gap in the management of dyslipidemia, by increasing the proportion of patients achieving LDL-C goals recommended to lower cardiovascular risk.

LDL cholesterol target achievement in heterozygous familial hypercholesterolemia patients according to 2019 ESC/EAS lipid guidelines: Implications for newer lipid-lowering treatments

BackgroundThe 2019 European guidelines (ESC/EAS) for the treatment of dyslipidaemias recommend more aggressive targets for low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia (FH). Current lipid-lowering treatment is often inadequate to achieve these targets. MethodsData from the HELLAS-FH registry were analysed to assess achievement of LDL-C targets in adults with FH based on the 2019 ESC/EAS guidelines. In patients who had not achieved LDL-C target, the maximally reduced LDL-C value was calculated after theoretical switch to rosuvastatin/ezetimibe 40/10 mg/day. The percentage of patients who remained candidates for proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) was then calculated. ResultsPatients (n = 1694, mean age 50.8 ± 14.7 years) had LDL-C levels 242 ± 71 mg/dL (6.3 ± 1.8 mmol/L) at diagnosis. Most treated patients were receiving statins (97.5%) and about half were on additional ezetimibe (47.5%). Based on the 2019 ESC/EAS guidelines the percentage of patients achieving LDL-C goals was only 2.7%. Following theoretical up titration to rosuvastatin/ezetimibe 40/10 mg, LDL-C target achievement rate would increase to 5.9%. In this scenario, most patients (55.9%) would be eligible for PCSK9i treatment. Following theoretical administration of a PCSK9i, LDL-C target achievement rate would rise to 57.6%. However, 42.4% of patients would still be eligible for further LDL-C lowering treatment. ConclusionsMost FH patients do not reach new LDL-C targets even if on maximum intensity statin/ezetimibe treatment. In this case, more than half of FH patients are candidates for PCSK9i therapy and a considerable proportion may still require additional LDL-C lowering.

Population health management of low-density lipoprotein cholesterol via a remote, algorithmic, navigator-executed program

Implementation of guideline-directed cholesterol management remains low despite definitive evidence establishing such measures reduce cardiovascular (CV) events, especially in high atherosclerotic CV disease (ASCVD) risk patients. Modern electronic resources now exist that may help improve health care delivery. While electronic medical records (EMR) allow for population health screening, the potential for coupling EMR screening to remotely delivered algorithmic population-based management has been less studied as a way of overcoming barriers to optimal cholesterol management. In an academically affiliated healthcare system, using EMR screening, we sought to identify 1,000 high ASCVD risk patients not meeting guideline-directed low-density lipoprotein-cholesterol (LDL-C) goals within specific system-affiliated primary care practices. Contacted patients received cholesterol education and were offered a remote, guideline-directed, algorithmic cholesterol management program executed by trained but non-licensed "navigators" under professional supervision. Navigators used telephone, proprietary software and internet resources to facilitate algorithm-driven, guideline-based medication initiation/titration, and laboratory testing until patients achieved LDL-C goals or exited the program. As a clinical effectiveness program for cholesterol guideline implementation, comparison was made to those contacted patients who declined program-based medication management, and received education only, along with their usual care. 1021 patients falling into guideline-defined high ASCVD risk groups warranting statin therapy (ASCVD, type 2 diabetes, LDL ≥ 190 mg/dL, calculated 10-year ASCVD risk ≥7.5%) and not achieving guideline-defined target LDL-C levels and/or therapy were identified and contacted. Among the 698 such patients who opted for program medication management, significant LDL-C reductions occurred in the total cohort (mean -65.4 mg/dL, 45% decrease), and each high ASCVD risk subgroup: ASCVD (-57.2 mg/dL, -48.0%); diabetes mellitus (-53.1 mg/dL, -40.0%); severe hypercholesterolemia (-76.3 mg/dL, -45.7%); elevated ASCVD 10-year risk (-62.8 mg/dL, -41.1%) (P<0.001 for all), without any significant complications. Among 20% of participants with reported statin intolerance, average LDL-C decreased from baseline 143 mg/dL to 85 mg/dL using mainly statins and ezetimibe, with limited PCSK9 inhibitor use. In comparison, eligible high ASCVD risk patients who were contacted but opted for education only, a 17% LDL-C decrease occurred over a similar timeframe, with 80% remaining with an LDL-C over 100 mg/dL. A remote, algorithm-driven, navigator-executed cholesterol management program successfully identified high ASCVD risk undertreated patients using EMR screening and was associated with significantly improved guideline-directed LDL-C control, supporting this approach as a novel strategy for improving health care access and delivery.

Reaching LDL-C Targets in Patients with Moderate, High, and Very High Risk for Cardiovascular Disease After Bariatric Surgery According to Different Guidelines.

Cardiovascular disease (CVD) is highly prevalent in obese patients and is the leading cause of death. High levels of plasma low-density lipoprotein cholesterol (LDL-C) are associated with higher coronary artery disease (CAD) risk. The aim of the study was to assess the impact of the Roux-en-Y gastric bypass on the achievement of the currently proposed cardiovascular prevention goals after 1year. We performed a retrospective analysis from a prospectively built database of patients who underwent a primary Roux-en-Y gastric bypass (RYGB) from 2004 to 2018. Patients with intermediate, high, or very high risk for CVD according to the 2018 AHA/ACC or the 2019 ESC/EAS guidelines were selected. An analysis of clinical and biochemical variables in 1year was performed. Logistic multivariate regressions were made to assess the impact of preoperative and weight loss parameters in the achievement of LDL-C goals. From 1039 patients, 70 met the selection criteria and were included in the analysis of the 2018 AHA/ACC guidelines, and 75 in the 2019 ESC/EAS guidelines. Mean decrease in LDL-C levels was 21.1 ± 40.2mg/dL 1year after surgery, and 29/34 patients were off medications. The percentage of patients achieving LDL-C goals according to the 2018 AHA/ACC guidelines was 27.1%, whereas according to the 2019 ESC/EAS guidelines, the percentages was 9.3%. The %TWL was associated with achieving LDL-C goals according to the 2018 AHA/ACC at 1year. RYGB induces a significant weight loss and an improvement in LDL-C levels 1year after surgery. The number of patients that reached the goals varies according to the guidelines used and ranged from 9.3 to 27.1%.

A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies.

IntroductionClinicians, payers, guideline committees, and policymakers support the use of high-intensity statins in patients at high risk for complications of cardiovascular disease (CVD). Guidelines and recommendations provide guidance on next steps for patients with inadequate low-density lipoprotein cholesterol (LDL-C) control on maximally tolerated statin or for those who are statin-intolerant. Ezetimibe and evolocumab improve CV outcomes when added to statins in high-CV-risk populations. The aim of the study was to compare evolocumab and ezetimibe for lipid-lowering efficacy and safety.MethodsWe summarized data from 1427 patients from three phase 3 evolocumab studies comparing double-blinded evolocumab vs. ezetimibe. These studies evaluated four distinct populations: those free of CVD receiving each agent as monotherapy, patients with CVD receiving add-on therapy to low- or high-intensity statin, and statin-intolerant patients. Lipid efficacy and safety were reported at week 12.ResultsAcross the studies, evolocumab reduced LDL-C by a mean 55–61% from baseline to week 12; ezetimibe lowered LDL-C by 18–20% from baseline (mean difference = 38–43% favoring evolocumab; p < 0.0001). This corresponded to absolute reductions in LDL-C of 60–104 mg/dL with evolocumab vs. 17–35 mg/dL with ezetimibe. Evolocumab also significantly improved other lipids and led to a higher percentage of patients achieving LDL-C goals vs. ezetimibe. Adverse events and discontinuation rates (oral and parenteral therapy) were balanced across groups, suggesting good tolerance and acceptance of both treatments.ConclusionsEvolocumab outperformed ezetimibe in efficacy and lipid goal attainment. Both products demonstrated good safety/tolerability. These data may help guide access decisions for high-risk patients with inadequate treatment response or intolerance to statin therapy.

Trends and predictors of high-intensity statin therapy and LDL-C goal achievement among Thai patients with acute coronary syndrome

BackgroundPrevious studies on the use of high-intensity statins and low-density lipoprotein cholesterol (LDL-C) goal achievement were mostly conducted in patients with acute coronary syndrome (ACS) receiving care before 2013. We aimed to determine trends and predictors of high-intensity statin therapy and LDL-C goal achievement in a more recent cohort of Thai ACS patients. MethodsWe analyzed data from electronic databases of ACS patients at a tertiary-care, teaching hospital in Thailand between 2013 and 2017. Trends and predictors of high-intensity statin therapy and LDL-C goal achievement after hospital discharge were determined with logistic regression analysis. ResultsAmong 1753 ACS patients, 987 (56.3%) received high-intensity statin at discharge. A higher proportion of ACS patients were prescribed high-intensity statins over time (p=0.033 for linear trend), rising from 10% in 2013 to 88% in 2017. Independent predictors of high-intensity statin therapy included age ≤75 years, a diagnosis of myocardial infarction, receiving P2Y12 inhibitors, and beta-blockers. Within 120 days after discharge, 427 (24.4%) patients had follow-up LDL-C measurements. Overall, 185 (43.3%) patients achieved LDL-C goals based on either of the following criteria: LDL-C <70mg/dL or ≥50% reduction in the baseline LDL-C. There was a non-significant trend (p=0.402 for linear trend) in the proportion of patients achieving LDL-C goals over the study period. Independent predictors of achieving LDL-C goal included high-intensity statin therapy after discharge and lower baseline LDL-C on admission. ConclusionsIn a more recent cohort of Thai ACS patients, a higher proportion of patients were prescribed high-intensity statins before discharge over the study period. However, the proportion of patients who achieved LDL-C goal did not increase accordingly. This finding should promote more discussion among health policy makers to improve statin treatment and quality of care for ACS patients.

Efficacy of alirocumab according to background statin type and dose: pooled analysis of 8 ODYSSEY Phase 3 clinical trials

Low-density lipoprotein cholesterol (LDL-C) reductions with the PCSK9 monoclonal antibody alirocumab may be affected by background statin dose due to increased PCSK9 levels with higher statin doses. Data from 8 Phase 3 trials conducted with background statin (n = 4629) were pooled by alirocumab dose (75 or 150 mg every 2 weeks) and control (placebo/ezetimibe), and analyzed by background statin type/dose. Overall, 58.4% received high-dose statins (atorvastatin 40–80 mg, rosuvastatin 20–40 mg, simvastatin 80 mg), 28.6% moderate-dose statins (atorvastatin 20–<40 mg, rosuvastatin 10–<20 mg, simvastatin 40–<80 mg), and 12.9% low-dose statins (atorvastatin <20 mg, rosuvastatin <10 mg, simvastatin <40 mg). Mean baseline PCSK9 levels were higher with high versus moderate and low statin doses (318.5 vs 280.6 ng/mL). Baseline LDL-C levels were similar across pools, regardless of statin intensity. No associations were observed between statin type/dose and LDL-C % change from baseline or % of patients achieving LDL-C goals at Week 24 for alirocumab versus control (interaction P-values non-significant). Incidence of adverse events was similar for alirocumab versus control, except for a higher rate of injection-site reactions with alirocumab. In summary, alirocumab provided consistent LDL-C reductions and was generally well tolerated independent of background statin type/dose.

Efficacy, safety and effect on biomarkers related to cholesterol and lipoprotein metabolism of rosuvastatin 10 or 20 mg plus ezetimibe 10 mg vs. simvastatin 40 or 80 mg plus ezetimibe 10 mg in high-risk patients: Results of the GRAVITY randomized study

ObjectivesCombination therapy may help high-risk patients achieve low-density lipoprotein cholesterol (LDL-C) goals. Impact of rosuvastatin 10 or 20 mg plus ezetimibe 10 mg (RSV10/EZE10 and RSV20/EZE10) has not been fully characterized previously. GRAVITY (NCT00525824) compared efficacy, safety and effect on biomarkers of RSV10/EZE10 and RSV20/EZE10 vs. simvastatin 40 mg and 80 mg plus EZE10 (SIM40/EZE10 and SIM80/EZE10) in patients with coronary heart disease (CHD) or CHD risk equivalent. MethodsAdult patients (n = 833) were randomized to RSV10/EZE10, RSV20/EZE10, SIM40/EZE10 or SIM80/EZE10. Following a 6-week dietary lead-in, patients received 6 weeks' statin monotherapy followed by same statin dose plus ezetimibe for 6 more weeks. Primary endpoint was LDL-C change from baseline to 12 weeks. ResultsSignificantly greater (p < 0.05) reductions in LDL-C and other atherogenic lipids were observed with RSV20/EZE10 vs. SIM40/EZE10 and SIM80/EZE10 and with RSV10/EZE10 vs. SIM40/EZE10. A significantly greater proportion of patients achieved LDL-C goals of <100 mg/dl and <70 mg/dl with RSV20/EZE10 vs. SIM40/EZE10 and SIM80/EZE10 and with RSV10/EZE10 vs. SIM40/EZE10. LDL-C was reduced ∼10–14% further with combination therapy vs. monotherapy. Statin monotherapy reduced cholesterol and bile acid synthesis biomarkers, ezetimibe reduced β-sitosterol (sterol absorption marker), and combination therapy achieved additive reductions in lipoprotein-associated phospholipase A2 mass and activity, free cholesterol and 7-ketocholesterol. Safety profiles of rosuvastatin/ezetimibe and simvastatin/ezetimibe combinations were comparable. ConclusionCo-administration of rosuvastatin 10 or 20 mg plus ezetimibe achieved significant improvements in lipid profiles in high-risk patients vs. simvastatin 40 or 80 mg plus ezetimibe.

Clinical and Economic Impact of Clinical Pharmacy Service on Hyperlipidemic Management in Hong Kong

To assess the clinical and economic outcomes of a clinical pharmacy service (CPS) in dyslipidemic management. This was a 24-month prospective controlled trial conducted at the lipid clinic of a public hospital in Hong Kong. In the intervention group, a clinical pharmacist assessed low-density lipoprotein cholesterol (LDL-C) levels and provided recommendations in accordance to the Adult Treatment Panel III (ATP III) guidelines. Medication compliance and the proper use of drugs were assessed. Education on healthy lifestyles was reinforced. Monthly telephone follow-ups were made to check on the progress of patients. In the control group, patients received usual medical care with no pharmacist intervention. Primary outcome was the percentage of patients achieving the ATP III LDL-C goal at the end of study. The estimated cost of such service was also evaluated. A total of 300 patients were recruited into the study (150 in intervention group and 150 in control group). In the intervention group, 58.7% patients achieved LDL-C goals compared with 45.3% in the control group (P < .05). The intervention group achieved 26.4%, 17.4%, and 30.0% mean reduction in LDL-C, total cholesterol (TC), and triglycerides (TG) levels, respectively, compared with 12.6%, 6.6%, and 11.5% in the control group (P < .05). The estimated cost for this clinical service was US$385/month for a total of 600 dyslipidemic patients seen per year. The results of this study demonstrate the positive impact CPS can have on achieving treatment goals in lipid management. Similar services for other problematic conditions such as hypertension and diabetes mellitus may also be benefited by similar CPSs.

Lipid Treatment Assessment Project 2

Information about physicians' adherence to cholesterol management guidelines remains scant. The present survey updates our knowledge of lipid management worldwide. Lipid levels were determined at enrollment in dyslipidemic adult patients on stable lipid-lowering therapy in 9 countries. The primary end point was the success rate, defined as the proportion of patients achieving appropriate low-density lipoprotein cholesterol (LDL-C) goals for their given risk. The mean age of the 9955 evaluable patients was 62+/-12 years; 54% were male. Coronary disease and diabetes mellitus had been diagnosed in 30% and 31%, respectively, and 14% were current smokers. Current treatment consisted of a statin in 75%. The proportion of patients achieving LDL-C goals according to relevant national guidelines ranged from 47% to 84% across countries. In low-, moderate-, and high-risk groups, mean LDL-C was 119, 109, and 91 mg/dL and mean high-density lipoprotein cholesterol was 62, 49, and 50 mg/dL, respectively. The success rate for LDL-C goal achievement was 86% in low-, 74% in moderate-, and 67% in high-risk patients (73% overall). However, among coronary heart disease patients with > or =2 risk factors, only 30% attained the optional LDL-C goal of <70 mg/dL. In the entire cohort, high-density lipoprotein cholesterol was <40 mg/dL in 19%, 40 to 60 mg/dL in 55%, and >60 mg/dL in 26% of patients. Although there is room for improvement, particularly in very-high-risk patients, these results indicate that lipid-lowering therapy is being applied much more successfully than it was a decade ago.

A COmparative study with rosuvastatin in subjects with METabolic Syndrome: results of the COMETS study†

The efficacy and safety of rosuvastatin, atorvastatin, and placebo were compared in patients with the metabolic syndrome. Patients with the metabolic syndrome with low-density lipoprotein cholesterol (LDL-C) > or =3.36 mmol/L (130 mg/dL) and multiple risk factors conferring a 10-year coronary heart disease risk score of >10% were randomized (2:2:1) to receive rosuvastatin 10 mg, atorvastatin 10 mg, or placebo for 6 weeks. Subsequently, the rosuvastatin 10 mg and placebo groups received rosuvastatin 20 mg and the atorvastatin 10 mg group received atorvastatin 20 mg for 6 weeks. LDL-C was reduced significantly more in patients receiving rosuvastatin 10 mg when compared with those receiving atorvastatin 10 mg at 6 weeks [intention-to-treat (ITT) population by randomized treatment: 41.7 vs. 35.7%, P < 0.001; ITT population by as-allocated treatment: 42.7 vs. 36.6%, P < 0.001]. Significant LDL-C reductions were also observed in patients receiving rosuvastatin when compared with those receiving atorvastatin at 12 weeks (48.9 vs. 42.5%, P < 0.001). More patients achieved LDL-C goals with rosuvastatin when compared with atorvastatin. Rosuvastatin increased high-density lipoprotein cholesterol significantly more than atorvastatin. Treatments were well tolerated. At equivalent doses, rosuvastatin had a significantly greater effect than atorvastatin in lowering LDL-C and improving the lipid profile and was well tolerated in patients with the metabolic syndrome.

Efficacy and Safety of Slow-release Fluvastatin 80 mg Daily in Chinese Patients with Hypercholesterolemia

Before this study, the efficacy and safety of doubling the dosage of fluvastatin from 40 mg/day to 80 mg/day in Chinese patients with primary hypercholesterolemia remained to be determined. In this open-label, active-controlled randomized 2-center study, patients with primary hypercholesterolemia were randomized to treatment with immediate-release fluvastatin 40 mg/day (n = 30) or slow-release fluvastatin 80 mg/day (n = 31) for 12 weeks. The primary efficacy variable was percent change in low-density lipoprotein (LDL) cholesterol level from baseline. Secondary efficacy variables were percent changes in total cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol levels, and the percent of patients achieving LDL cholesterol goals of the US National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) II. Both fluvastatin dosages (40 mg/day vs 80 mg/day) effectively reduced LDL cholesterol (-22.5% vs -29.9%; p = 0.087), total cholesterol (-17.3% vs -22.5%; p = 0.140), and triglyceride levels (-14.0% vs -12.3%; p = 0.813) (all p < 0.0001 for comparison with baseline), and slightly increased HDL cholesterol levels (+5.2% vs +5.6%; p = 0.917), after 12 weeks of treatment. The percent of patients achieving LDL cholesterol goals of the NCEP ATP II was 37% versus 65% (p < 0.05). The adverse event profiles for the 2 fluvastatin dosages were similar. In Chinese patients with primary hypercholesterolemia, doubling the dosage of fluvastatin from 40 to 80 mg once daily was effective and safe regarding reduction of LDL cholesterol level, and allowed more patients to achieve LDL cholesterol goals of the NCEP ATP II.

A new reality: achieving cholesterol-lowering goals in clinical practice.

Physicians often fail to achieve recommended low-density lipoprotein (LDL) cholesterol goals for their patients using lipid-lowering therapies in the primary care setting. A variety of factors may contribute to this failure, including inadequate effectiveness of lipid-lowering drugs in reducing LDL cholesterol at commonly used doses. In the Lipid Assessment Treatment Project (L-TAP), for example, the success rates for lipid-regulating therapies and treatments according to National Cholesterol Education Program (NCEP) Adult Treatment Panel II (ATP II) LDL cholesterol goals were 43% for bile acid sequestrants, 39% for niacin, 32% for gemfibrozil, 28% for psyllium fiber, 40% for statins, and 40% for combination therapy. Rosuvastatin is a new statin that has been shown to achieve significantly greater reductions in LDL cholesterol compared with pravastatin, simvastatin, and atorvastatin in primary hypercholesterolemia and enabled greater proportions of patients to achieve LDL cholesterol goals. Similarly, rosuvastatin proved superior to atorvastatin in lowering LDL cholesterol in patients with familial hypercholesterolemia, with more patients achieving LDL cholesterol goals. Data from these trials suggest that rosuvastatin is as safe and well tolerated as other statins. The availability of lipid-lowering drugs with greater LDL cholesterol-lowering effects could simplify the approach to coronary heart disease risk reduction in primary care.

Attaining United States and European Guideline LDL-cholesterol Levels with Simvastatin in Patients with Coronary Heart Disease (the GOALLS Study)

SummaryThe effectiveness and safety of simvastatin in reducing low-density lipoprotein cholesterol (LDL-C) to target levels in patients with coronary heart disease (CHD) were evaluated in the GOALLS (Getting to Appropriate LDL-C Levels with Simvastatin) study. This multinational, multicentre, prospective, open-label, study consisted of a six-week diet washout period followed by a 14-week titrate-to-goal treatment period with simvastatin. One hundred and ninety-eight men and women with documented CHD and a fasting LDL-C level between 115 mg/dl (3.0 mmol/l) and 180 mg/dl (4.7 mmol/l) and triglycerides (TGs) ≤ 400 mg/dl (4.5 mmol/l) were enrolled. The patients were started on 20 mg simvastatin with dose titration up to 80 mg if the LDL-C remained above 100 mg/dl at weeks 6 and 10. The key efficacy parameters were the percentage of patients achieving US and European LDL-C goals [≤ 100 mg/dl (2.6 mmol/l) and ≤ 115 mg/dl(3.0 mmol/l), respectively]. Safety was evaluated by monitoring laboratory tests and recording adverse events.After 14 weeks of simvastatin (20–80 mg) treatment, approximately 90% of the patients achieved LDL-C goals according to US (87%) and European (94%) guidelines. Most patients (72–93%) achieved target LDL-C levels on 20 mg simvastatin. An estimated 14% of the patients required titration to the 80 mg dose. Treatment with simvastatin (20–80 mg) produced statistically significant improvements in all measured lipid variables by the end of the study. The mean reductions in total cholesterol and LDL-C, and the median reduction in TG, were 28%, 41% and 16%, respectively. The increase in high-density lipoprotein cholesterol and apolipoprotein A-1 were 5% and 4%, respectively. Simvastatin was well tolerated across the dosage range.In conclusion, simvastatin, 20–80 mg/day, was safe and highly effective at reducing LDL-C levels. The recommended US and European LDL-C treatment goals were achieved in approximately 90% of the patients. These goals were similarly achieved for a variety of high-risk sub-groups (hypertensives, diabetics and elderly patients).