Abstract 13130: Efficacy and Safety of Bempedoic Acid by Sex: Pooled Analyses From Phase 3 Trials

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anne C Goldberg ◽  
Maciej Banach ◽  
Alberico L Catapano ◽  
P Barton Duell ◽  
Lawrence A Leiter ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherosclerotic Cardiovascular Disease ◽  
Efficacy And Safety ◽  
Atp Citrate Lyase ◽  
Statin Intolerance ◽  
Phase 3 ◽  
Double Blind ◽  
Citrate Lyase ◽  
History Of

Introduction: Bempedoic acid (BA), an ATP-citrate lyase inhibitor, lowers low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia. Objective: To report efficacy and safety of BA by sex in patients with elevated LDL-C. Methods: Data were pooled from 4 phase 3 randomized (2:1), double-blind studies investigating oral BA (180 mg once daily) vs placebo for 12 weeks to 52 weeks in adults receiving maximally tolerated statins who required additional LDL-C lowering, analyzed by sex. The primary efficacy endpoint was % change in LDL-C from baseline to week 12. Results were analyzed in cohorts with atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (“ASCVD/HeFH on statins pool”, n=3009) or history of statin intolerance (“statin intolerant pool”, n=614). Safety assessments included treatment-emergent adverse events (TEAEs). Results: Of all participants, 34.3% were women. Significant LDL-C lowering from baseline with BA vs placebo was demonstrated in both pools and sexes ( P < 0.001; Table 1 ), with greater lowering in women vs men in the ASCVD/HeFH on statins pool ( P = 0.04). Rates of TEAEs were similar across groups ( Table 2 ). Rates of common TEAEs were similar in both pools and sexes, except urinary tract infection (men: BA, 2.8%; placebo, 3.0%; women: BA, 8.0%; placebo, 10.3%) and pain in extremity (men: BA, 2.5%; placebo, 1.2%; women: BA, 4.2%; placebo, 2.9%), which occurred more frequently in women. Conclusion: BA lowered LDL-C significantly in both women and men, with greater effect in women vs men in both pools, and a safety profile generally comparable to placebo in both sexes.

Have we learnt all from IMPROVE-IT? Part II. Subanalyses on the ef- fects of ezetimibe added to statin therapy on selected clinical and laborato- ry outcomes, cost effectiveness, guideline and clinical implications

2020 ◽  
Vol 18 ◽  
Author(s):  
Zlatko Fras ◽  
Dimitri P. Mikhailidis
Keyword(s):  
Statin Therapy ◽  
Artery Bypass ◽  
Low Density Lipoprotein ◽  
Bypass Graft ◽  
Density Lipoprotein ◽  
Drug Discontinuation ◽  
Atherosclerotic Cardiovascular Disease ◽  
History Of ◽  
Risk Cost ◽  
Cardiovascular Biomarkers

: In this second part of a review of the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), we discuss the findings in relation to patients with stroke, the ACS phenotype, history of coronary artery bypass graft surgery, heart failure, concurrent polyvascular atherosclerotic cardiovascular disease (ASCVD) and diabetes mellitus, and different levels of expression of selected cardiovascular biomarkers. The combination therapy was proven safe, and drug discontinuation rates were not increased by adding ezetimibe. Since both statins and ezetimibe are now almost globally generically available, we can conclude that for secondary prevention of ASCVD, adding ezetimibe to high-intensity statin therapy further reduces low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk cost-effectively.

scholarly journals Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Kausik K. Ray ◽  
Stefano Del Prato ◽  
Dirk Müller-Wieland ◽  
Bertrand Cariou ◽  
Helen M. Colhoun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Open Label ◽  
Double Blind ◽  
Mixed Dyslipidemia

Abstract Background Individuals with diabetes often have high levels of atherogenic lipoproteins and cholesterol reflected by elevated low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and LDL particle number (LDL-PN). The presence of atherosclerotic cardiovascular disease (ASCVD) increases the risk of future cardiovascular events. We evaluated the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, alirocumab, among individuals with type 2 diabetes (T2DM), high LDL-C or non-HDL-C, and established ASCVD receiving maximally tolerated statin in ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) and DM-INSULIN (NCT02585778). Methods In DM-DYSLIPIDEMIA, individuals with T2DM and mixed dyslipidemia (non-HDL-C ≥ 100 mg/dL; n = 413) were randomized to open-label alirocumab 75 mg every 2 weeks (Q2W) or usual care (UC) for 24 weeks, with UC options selected before stratified randomization. In DM-INSULIN, insulin-treated individuals with T2DM (LDL-C ≥ 70 mg/dL; n = 441) were randomized in a double-blind fashion to alirocumab 75 mg Q2W or placebo for 24 weeks. Study participants also had a glycated hemoglobin < 9% (DM-DYSLIPIDEMIA) or < 10% (DM-INSULIN). Alirocumab dose was increased to 150 mg Q2W at week 12 if week 8 LDL-C was ≥ 70 mg/dL (DM-INSULIN) or non-HDL-C was ≥ 100 mg/dL (DM-DYSLIPIDEMIA). Lipid reductions and safety were assessed in patients with ASCVD from these studies. Results This analysis included 142 DM-DYSLIPIDEMIA and 177 DM-INSULIN participants with ASCVD, including 95.1% and 86.4% with coronary heart disease, and 32.4% and 49.7% with microvascular diabetes complications, respectively. At week 24, alirocumab significantly reduced LDL-C, non-HDL-C, ApoB, and LDL-PN from baseline versus control. This translated into a greater proportion of individuals achieving non-HDL-C < 100 mg/dL (64.6% alirocumab/23.8% UC [DM-DYSLIPIDEMIA]; 65.4% alirocumab/14.9% placebo [DM-INSULIN]) and ApoB < 80 mg/dL (75.1% alirocumab/35.4% UC and 76.8% alirocumab/24.8% placebo, respectively) versus control at week 24 (all P < 0.0001). In pooling these studies, 66.4% (alirocumab) and 67.0% (control) of individuals reported treatment-emergent adverse events. The adverse event pattern was similar with alirocumab versus controls. Conclusions Among individuals with T2DM and ASCVD who had high non-HDL-C/LDL-C levels despite maximally tolerated statin, alirocumab significantly reduced atherogenic cholesterol and LDL-PN versus control. Alirocumab was generally well tolerated. Trial registration Clinicaltrials.gov. NCT02642159. Registered 30 December 2015 and Clinicaltrials.gov. NCT02585778. Registered 23 October 2015

scholarly journals The effect of (−)-hydroxycitrate on the activity of the low-density-lipoprotein receptor and 3-hydroxy-3-methylglutaryl-CoA reductase levels in the human hepatoma cell line Hep G2

1990 ◽  
Vol 272 (1) ◽  
pp. 181-186 ◽  
Author(s):  
T A Berkhout ◽  
L M Havekes ◽  
N J Pearce ◽  
P H E Groot
Keyword(s):  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Hep G2 ◽  
Atp Citrate Lyase ◽  
Hmg Coa Reductase ◽  
Synthetic Pathway ◽  
Citrate Lyase ◽  
Coa Reductase

(-)-Hydroxycitrate, a potent inhibitor of ATP citrate-lyase, was tested in Hep G2 cells for effects on cholesterol homoeostasis. After 2.5 h and 18 h incubations with (-)-hydroxycitrate at concentrations of 0.5 mM or higher, incorporation of [1,5-14C]citrate into fatty acids and cholesterol was strongly inhibited. This most likely reflects an effective inhibition of ATP citrate-lyase. Cholesterol biosynthesis was decreased to 27% of the control value as measured by incorporations from 3H2O, indicating a decreased flux of carbon units through the cholesterol-synthetic pathway. After 18 h preincubation with 2 mM-(-)-hydroxycitrate, the cellular low-density-lipoprotein (LDL) receptor activity was increased by 50%, as determined by the receptor-mediated association and degradation. Measurements of receptor-mediated binding versus LDL concentration suggests that this increase was due to an increase in the numbers of LDL receptors. Simultaneously, enzyme levels of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase as determined by activity measurements increased 30-fold. Our results suggest that the increases in HMG-CoA reductase and the LDL receptor are initiated by the decreased flux of carbon units in the cholesterol-synthetic pathway, owing to inhibition of ATP citratelyase. A similar induction of HMG-CoA reductase and LDL receptor was also found after preincubations of cells with 0.3 microM-mevinolin, suggesting that the underlying mechanism for this induction is identical for both drugs.

Abstract 14270: The Effect of Evinacumab on Apheresis Eligibility in Patients With Homozygous Familial Hypercholesterolemia

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Frederick J Raal ◽  
Robert S Rosenson ◽  
Laurens F Reeskamp ◽  
G. Kees Hovingh ◽  
John J Kastelein ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Human Monoclonal Antibody ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Homozygous Familial Hypercholesterolemia ◽  
Double Blind ◽  
Lipid Disorder ◽  
Artery Disease

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic lipid disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Evinacumab, a fully human monoclonal antibody against angiopoietin-like protein 3, has demonstrated approximately 50% reductions in LDL-C in HoFH patients when added to maximally tolerated lipid-lowering therapies. Objective: In this post-hoc analysis, we assessed the effect of evinacumab on the eligibility for apheresis using predefined US and EU apheresis criteria. Methods: This was a double-blind, placebo-controlled, 24-week phase 3 trial (NCT03399786) that randomized patients 2:1 to evinacumab 15 mg/kg intravenously every 4 weeks (Q4W; n=43) or placebo (n=22). We assessed the proportion of patients who met per protocol US apheresis criteria (LDL-C ≥300 mg/dL), newer US criteria for FH (LDL-C ≥300 mg/dL or LDL-C ≥160 mg/dL with coronary heart disease or peripheral artery disease) and per protocol EU apheresis criteria (LDL-C >160 mg/dL [primary prevention] or >120 mg/dL [secondary prevention]) at baseline and week 24. Results: Under the newer US criteria (2018), 62.8% (n=27) of evinacumab-treated patients and 54.5% (n=12) placebo-treated patients qualified for apheresis at baseline (Table). Following 24 weeks of treatment, 48.8% of all evinacumab versus 9.1% of all placebo patients no longer qualified for apheresis. Similar results were observed using EU apheresis criteria, where 46.5% of evinacumab-treated patients shifted from qualifying for apheresis at baseline to not qualifying at week 24, compared with 4.5% of placebo-treated patients. The majority of evinacumab (65.1%) and placebo (68.2%) patients did not qualify for per protocol US apheresis at baseline, however a shift of 27.9% and 9.1% was observed, respectively. Conclusions: Evinacumab has the potential to reduce the need for apheresis in patients with HoFH.

Efficacy and Safety of Cerivastatin 0.8 mg in Patients with Hypercholesterolaemia: The Pivotal Placebo-Controlled Clinical Trial

2000 ◽  
Vol 28 (2) ◽  
pp. 47-68 ◽  
Author(s):  
W Insull ◽  
J Isaacsohn ◽  
P Kwiterovich ◽  
P Ma ◽  
R Brazg ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Heart Association ◽  
Pharmacological Therapy ◽  
Apolipoprotein A1 ◽  
Lipoprotein Cholesterol ◽  
Controlled Clinical Trial ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Primary Hypercholesterolaemia

This pivotal, multicentre, double-blind, parallel-group study evaluated the efficacy and safety of cerivastatin 0.8 mg. Patients with primary hypercholesterolaemia were randomized, after 10 weeks' dietary stabilization on an American Heart Association (AHA) Step I diet, to treatment with cerivastatin 0.8 mg ( n = 776), cerivastatin 0.4 mg ( n = 195) or placebo ( n = 199) once daily for 8 weeks. Cerivastatin 0.8 mg reduced mean low density lipoprotein-cholesterol (LDL-C) by 41.8% compared with cerivastatin 0.4 mg (–35.6%, P < 0.0001) or placebo. In 90% of patients receiving cerivastatin 0.8 mg LDL-C was reduced by 23.9–58.4% (6th–95th percentile). Overall attainment of the National Cholesterol Education Program (NCEP) goal was achieved by 84% of patients receiving cerivastatin 0.8 mg and by 59% of those with coronary heart disease (CHD). In the sub-population meeting the NCEP criteria for pharmacological therapy for LDL-C reduction, 74.6% of patients, including the 59% with CHD, reached the goal with cerivastatin 0.8 mg. Cerivastatin 0.8 mg also reduced mean total cholesterol by 29.9%, apolipoprotein B by 33.2% and median triglycerides by 22.9% (all P < 0.0001). Mean high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 were elevated 8.7% ( P < 0.0001) and 4.5% ( P < 0.0001), respectively, by cerivastatin 0.8 mg. Reductions of triglyceride and elevation in HDL-C were dependent upon triglyceride baseline levels; in patients having baseline triglyceride levels 250–400 mg/dl, cerivastatin 0.8 mg reduced median triglycerides by 29.5% and elevated HDL-C by 13.2%. Cerivastatin 0.8 mg was well tolerated. The most commonly reported adverse events included headache, pharyngitis and rhinitis (4–6%). Symptomatic creatine kinase elevations > 10 times upper limit of normal occurred in 0%, 1% and 0.9% of patients receiving placebo, cerivastatin 0.4 mg or cerivastatin 0.8 mg, respectively. Cerivastatin 0.8 mg is an effective and safe treatment for patients with primary hypercholesterolaemia who need aggressive LDL-C lowering in order to achieve NCEP-recommended levels.

scholarly journals Efficacy and safety of berberine for dyslipidemia: study protocol for a randomized double-blind placebo-controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ying Zhao ◽  
Yuan-Yuan Yang ◽  
Bao-Lin Yang ◽  
Ya-Wei Du ◽  
Da-Wei Ren ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Controlled Trial ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Controlled Clinical Trial ◽  
Atherosclerotic Cardiovascular Disease ◽  
Efficacy And Safety ◽  
Clinical Trial Registry ◽  
High Quality ◽  
Double Blind

Abstract Background Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease and a leading cause of death worldwide. The clinical utility of commonly used lipid-lowering drugs such as statins and fibrates is sometimes limited by the occurrence of various adverse reactions. Recently, berberine (BBR) has received increasing attention as a safer and more cost-effective option to manage dyslipidemia. Thus, a high-quality randomized controlled trial to evaluate the efficacy and safety of BBR in the treatment of dyslipidemia is deemed necessary. Methods/design This is a randomized, double-blind, and placebo-controlled clinical trial. A total of 118 patients with dyslipidemia will be enrolled in this study and randomized into two groups at a ratio of 1:1. BBR or placebo will be taken orally for 12 weeks. The primary outcome is the percentage of low-density lipoprotein cholesterol reduction at week 12. Other outcome measures include changes in other lipid profiles, high sensitivity C-reactive protein, blood pressure, body weight, Bristol Stool Chart, traditional Chinese medicine symptom form, adipokine profiles, and metagenomics of intestinal microbiota. Safety assessment includes general physical examination, blood and urine routine test, liver and kidney function test, and adverse events. Discussion This trial may provide high-quality evidence on the efficacy and safety of BBR for dyslipidemia. Importantly, the findings of this trial will help to identify patient and disease characteristics that may predict favorable outcomes of treatment with BBR and optimize its indication for clinical use. Trial registration Chinese Clinical Trial Registry ChiCTR1900021361. Registered on 17 February 2019.

scholarly journals Stroke Prevention With the PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) Inhibitor Evolocumab Added to Statin in High-Risk Patients With Stable Atherosclerosis

Stroke ◽  
2020 ◽  
Vol 51 (5) ◽  
pp. 1546-1554 ◽  
Author(s):  
Robert P. Giugliano ◽  
Terje R. Pedersen ◽  
Jeffrey L. Saver ◽  
Peter S. Sever ◽  
Anthony C. Keech ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Arterial Disease ◽  
Hazard Ratio ◽  
Proprotein Convertase ◽  
Vascular Events ◽  
Unique Identifier ◽  
Double Blind ◽  
History Of

Background and Purpose— The PCSK9 (proprotein convertase subtilisin-kexin type 9) monoclonal antibody evolocumab lowered LDL (low-density lipoprotein) cholesterol by 59% to 0.8 (0.5–1.2) mmol/L and significantly reduced major vascular events in the FOURIER trial (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk). Herein, we report the results of a prespecified analysis of cerebrovascular events in the overall trial population and in patients stratified by prior stroke. Methods— FOURIER was a randomized, double-blind trial comparing evolocumab versus placebo in patients with established atherosclerosis, additional risk factors, and LDL cholesterol levels ≥1.8 (or non-HDL [high-density lipoprotein] ≥2.6 mmol/L) on statin therapy. The median follow-up was 2.2 years. We analyzed the efficacy of evolocumab to reduce overall stroke and stroke subtypes, as well as the primary cardiovascular composite end point by subgroups according to a history of stroke. Results— Among the 27 564 patients, 469 (1.7%) experienced a total of 503 strokes of which 421 (84%) were ischemic. Prior ischemic stroke, diabetes mellitus, elevated CRP (C-reactive protein), history of heart failure, older age, nonwhite race, peripheral arterial disease, and renal insufficiency were independent predictors of stroke. Evolocumab significantly reduced all stroke (1.5% versus 1.9%; hazard ratio, 0.79 [95% CI, 0.66–0.95]; P =0.01) and ischemic stroke (1.2% versus 1.6%; hazard ratio, 0.75 [95% CI, 0.62–0.92]; P =0.005), with no difference in hemorrhagic stroke (0.21% versus 0.18%; hazard ratio, 1.16 [95% CI, 0.68–1.98]; P =0.59). These findings were consistent across subgroups, including among the 5337 patients (19%) with prior ischemic stroke in whom the hazard ratios (95% CIs) were 0.85 (0.72–1.00) for the cardiovascular composite, 0.90 (0.68–1.19) for all stroke, and 0.92 (0.68–1.25) for ischemic stroke ( P interactions, 0.91, 0.22, and 0.09, respectively, compared with patients without a prior ischemic stroke). Conclusions— Inhibition of PCSK9 with evolocumab added to statin in patients with established atherosclerosis reduced ischemic stroke and cardiovascular events in the total population and in key subgroups, including those with prior ischemic stroke. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01764633.

scholarly journals Efficacy and safety of adjunctive lacosamide in the treatment of primary generalised tonic-clonic seizures: a double-blind, randomised, placebo-controlled trial

2020 ◽  
Vol 91 (10) ◽  
pp. 1067-1075 ◽  
Author(s):  
David G Vossler ◽  
Susanne Knake ◽  
Terence J O'Brien ◽  
Masako Watanabe ◽  
Melissa Brock ◽  
...  
Keyword(s):  
Treatment Duration ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Adjunctive Treatment ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Kaplan Meier ◽  
History Of ◽  
Clonic Seizures

ObjectiveTo evaluate efficacy and safety of lacosamide (up to 12 mg/kg/day or 400 mg/day) as adjunctive treatment for uncontrolled primary generalised tonic-clonic seizures (PGTCS) in patients (≥4 years) with idiopathic generalised epilepsy (IGE).MethodsPhase 3, double-blind, randomised, placebo-controlled trial (SP0982; NCT02408523) in patients with IGE and PGTCS taking 1–3 concomitant antiepileptic drugs. Primary outcome was time to second PGTCS during 24-week treatment.Results242 patients were randomised and received ≥1 dose of trial medication (lacosamide/placebo: n=121/n=121). Patients (mean age: 27.7 years; 58.7% female) had a history of generalised-onset seizures (tonic-clonic 99.6%; myoclonic 38.8%; absence 37.2%). Median treatment duration with lacosamide/placebo was 143/65 days. Risk of developing a second PGTCS during 24-week treatment was significantly lower with lacosamide than placebo (Kaplan-Meier survival estimates 55.27%/33.37%; HR 0.540, 95% CI 0.377 to 0.774; p<0.001; n=118/n=121). Median time to second PGTCS could not be estimated for lacosamide (>50% of patients did not experience a second PGTCS) and was 77.0 days for placebo. Kaplan-Meier estimated freedom from PGTCS at end of the 24-week treatment period (day 166) for lacosamide/placebo was 31.3%/17.2% (difference 14.1%; p=0.011). More patients on lacosamide than placebo had ≥50% (68.1%/46.3%) or ≥75% (57.1%/36.4%) reduction from baseline in PGTCS frequency/28 days, or observed freedom from PGTCS during treatment (27.5%/13.2%) (n=119/n=121). 96/121 (79.3%) patients on lacosamide had treatment-emergent adverse events (placebo 79/121 (65.3%)), most commonly dizziness (23.1%), somnolence (16.5%), headache (14.0%). No patients died during the trial.ConclusionsLacosamide was efficacious and generally safe as adjunctive treatment for uncontrolled PGTCS in patients with IGE.

P5364Safety profile of bempedoic acid: pooled analysis of 4 phase 3 clinical trials

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C M Ballantyne ◽  
M Banach ◽  
A L Catapano ◽  
P B Duell ◽  
U Laufs ◽  
...  
Keyword(s):  
Uric Acid ◽  
Safety Profile ◽  
Fatal Outcome ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Drug Discontinuation ◽  
Lipid Lowering Therapy ◽  
Atp Citrate Lyase ◽  
Phase 3 ◽  
Double Blind

Abstract Background/Introduction Bempedoic acid (BA), an oral, first-in-class, ATP-citrate lyase inhibitor, lowers low-density lipoprotein cholesterol (LDL-C) in patients who do not achieve sufficient lipid lowering with guideline-recommended first-line therapies. Purpose We evaluated the safety profile of BA in phase 3 trials. Methods Data were pooled from 4 randomised, double-blind, placebo-controlled studies that enrolled patients with hyperlipidaemia who were receiving stable lipid-lowering therapy (LLT; maximally tolerated statins +/− nonstatin therapies) and required additional LDL-C lowering. Patients were randomised (2:1) to BA 180 mg or placebo daily for 12 to 52 weeks. Results Median exposure for 3621 patients (2424 BA, 1197 placebo) was 363 days. Background LLT included a statin +/− other LLT (83.8%), nonstatin LLT alone (9.4%), or none (6.8%). Adverse event (AE) and serious AE rates were similar between groups (Table). The most common AEs in the BA and placebo groups were nasopharyngitis (7.4% vs 8.9%), myalgia (4.9% vs 5.3%), and urinary tract infection (4.5% vs 5.5%). Rates of new-onset/worsening diabetes were 4.0% for BA and 5.6% for placebo. No AEs leading to discontinuation differed by ≥0.5% between treatments. All fatal AEs were judged by the investigator as unrelated to treatment. A trend was observed for a lower 3-component major adverse cardiac event rate with BA vs placebo (hazard ratio, 0.85; 95% confidence interval: 0.53 to 1.37). Changes in uric acid, creatinine, and haemoglobin were apparent at week 4, stable over time, and reversible after stopping BA. Gout occurred in 1.4% and 0.4% of patients in the BA and placebo groups, respectively. The safety profile of BA was consistent across background therapies, demographics, and disease characteristics. Table 1. Safety summary Placebo (n=1197) BA (n=2424) Any AE / SAE, % (n) 72.5 (868) / 13.3 (159) 73.1 (1171) / 14.1 (341) Drug discontinuation due to an AE, % (n) 7.8 (93) 11.3 (273) AE with a fatal outcome, % (n) 0.3 (4) 0.8 (19) Aminotransferase elevation >3 x ULN, % (n) 0.3 (3) 0.7 (18) Aminotransferase elevation >5 x ULN, % (n) 0.2 (2) 0.2 (6) Creatine kinase elevation >5 x ULN, % (n) 0.2 (2) 0.3 (8) Creatinine, mean change at week 12, mg/dL −0.002±0.11 0.046±0.12 Uric acid, mean change at week 12, mg/dL −0.02±0.82 0.82±0.97 Haemoglobin, mean change at week 12, g/dL 0.06±0.69 −0.31±0.71 Conclusion(s) BA added to LLT was well tolerated, with a safety profile comparable to placebo.

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