Effect of alirocumab on lipids and lipoproteins in individuals with metabolic syndrome without diabetes: Pooled data from 10 phase 3 trials.

AimsThis analysis assessed the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in patients with or without metabolic syndrome (MetS) using pooled data from 10 phase 3 ODYSSEY trials.Materials and methodsData from 4983 randomized patients (1940 with MetS; 1642 with diabetes excluded) were assessed in subgroups by MetS status. Efficacy data were analysed in 4 pools per study design: 2 placebo-controlled pools (1 using alirocumab 150 mg every 2 weeks [Q2W], 1 using 75/150 mg Q2W) with background statin, and 2 ezetimibe-controlled pools (both alirocumab 75/150 mg Q2W), 1 with and 1 without background statin. Alirocumab 75/150 mg indicates possible dose increase from 75 to 150 mg at Week 12 based on Week 8 LDL-C.ResultsLDL-C percentage reduction from baseline at Week 24 with alirocumab was 63.9% (MetS) and 56.8% (non-MetS) in the pool of alirocumab 150 mg Q2W, and 42.2% to 52.2% (MetS) and 45.0% to 52.6% (non-MetS) in 3 pools using 75/150 mg Q2W. Levels of other lipid and lipoprotein parameters were also improved with alirocumab treatment, including apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein(a) and HDL-C. Overall, the percentage change at Week 24 in LDL-C and other lipids and lipoproteins did not vary by MetS status. Adverse event rates were generally similar between treatment groups, regardless of MetS status; injection-site reactions occurred more frequently in alirocumab vs control groups.ConclusionsAcross study pools, alirocumab-associated reductions in LDL-C, apolipoprotein B, and non-HDL-C were significant vs control, and did not vary by MetS status

Alirocumab versus usual lipid-lowering care as add-on to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia:The ODYSSEY DM-DYSLIPIDEMIA randomized trial

Individuals with type 2 diabetes (T2DM) and mixed dyslipidaemia represent a high-risk and difficult-to-treat population. ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) compared alirocumab, a proprotein convertase subtilisin-kexin type 9 inhibitor, with usual care (UC) in individuals with T2DM and mixed dyslipidaemia not optimally managed by maximally-tolerated statins

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

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

Efficacy and safety of alirocumab in individuals with type 2 diabetes mellitus with or without mixed dyslipidaemia : Analysis of the ODYSSEY LONG TERM trial

Background and aims: Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, significantly reduces low-density lipoprotein cholesterol (LDL-C). We evaluated the efficacy and safety of alirocumab in individuals with type 2 diabetes mellitus (T2DM) with versus without mixed dyslipidaemia (MDL, defined as baseline LDL-C >= 70 mg/dL [1.8 mmol/L] and triglycerides >= 150mg/dL [1.7 mmol/L]). Methods: Data from 812 individuals with T2DM, from the placebo-controlled, 78-week, Phase 3 ODYSSEY LONG TERM trial of alirocumab 150mg every 2 weeks (Q2W), on a background of maximally tolerated statins +/- other lipid-lowering therapies, were pooled according to MDL status. Efficacy endpoints included percentage change from baseline to Week 24 in calculated LDL-C and other lipids/lipoproteins. Results: In individuals with T2DM who received alirocumab 150mg Q2W, mean LDL-C changes from baseline to Week 24 were -62.6% (vs. -6.0% with placebo) in those with MDL and -56.1% (vs. 5.6%) in those without MDL, with no significant between-group difference (p-interaction = 0.0842). Risk-based LDL-C goals ( Conclusions: Reductions in LDL-C and other lipids with alirocumab, as well as safety and tolerability, were comparable between individuals with T2DM and with versus without MDL. (c) 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Peer reviewe

Efficacy and Safety of Alirocumab 300 mg Every 4 Weeks in Individuals With Type 2 Diabetes on Maximally Tolerated Statin

BACKGROUND: Individuals with diabetes and elevated LDL-C are at particularly high risk of atherosclerotic cardiovascular disease. ODYSSEY CHOICE I (NCT01926782) assessed alirocumab 300 mg every 4 weeks (Q4W) in patients with hypercholesterolemia. We evaluated alirocumab efficacy and safety in a patient subgroup with type 2 diabetes (T2DM) on maximally tolerated statins with/without other lipid-lowering therapies. METHODS: CHOICE I study participants received either alirocumab 300 mg Q4W (n=458, including 96 with T2DM) or placebo (n=230, including 50 with T2DM) for 48 weeks, with alirocumab dose adjustment to 150 mg Q2W at Week (W)12 if W8 LDL-C levels were ≥70/100 mg/dL, depending on cardiovascular risk, or if LDL-C reduction was <30% from baseline. Efficacy endpoints included percentage change from baseline to W24 for LDL-C and other lipids, and time-averaged LDL-C over W21-24. RESULTS: In individuals with T2DM, LDL-C reductions from baseline to W24 and average of W21-24 were significantly greater with alirocumab (-61.6% and -68.8% vs placebo, respectively). At W24, alirocumab also significantly reduced levels of non-HDL-C, apolipoprotein B, triglycerides, and lipoprotein (a). At W24, 85.9% (alirocumab) and 12.5% (placebo) of individuals reached both non-HDL-C <100 mg/dL and LDL-C <70 mg/dL. At W12, 18% of alirocumab-treated individuals received dose adjustment. Most common treatment-emergent adverse events were upper respiratory tract infection and injection-site reaction. No clinically significant changes in fasting plasma glucose and glycated hemoglobin were observed. CONCLUSIONS: In individuals with T2DM, alirocumab 300 mg Q4W dosing regimen is generally well tolerated and efficacious in reducing atherogenic lipoproteins represented by LDL-C and non-HDL-C

Lasten fyysinen aktiivisuus : Lapin ja Pohjois-Pohjanmaan 3.- ja 5.-luokkalaiset

Opinnäytetyömme tavoitteena oli saada tietoa Lapin ja Pohjois-Pohjanmaan 3.- ja 5.-luokkalaisten fyysisestä aktiivisuudesta. Työmme tarkoituksena oli selvittää, liikkuvatko lapset liikuntasuositusten mukaisesti ja näin ollen terveytensä kannalta riittävästi. Lisäksi selvitimme, kuinka paljon ja millä intensiteetillä lapset liikkuivat, sekä kuinka paljon he viettivät aikaa istuen ja makuulla valveillaoloajastaan. Työmme tulokset antavat aluekohtaista tietoa, jota voidaan hyödyntää tutkimusalueiden lasten liikkumisen kehittämisessä. Työmme oli määrällinen tutkimus, jossa tutkimustietoa kerättiin objektiivisesti liikemittareiden avulla. Liikemittarilla kerättiin tietoa lasten päivittäisestä liikkumisesta vähintään neljän päivän ajalta. Työmme aineisto pohjautuu LIITU 2016 - tutkimuksen aineistoon. Tutkimus toteutettiin keväällä 2016, ja tutkimuksemme otos koostui 394 alakouluikäisestä lapsesta. Teimme tutkimuksen yhteistyössä UKK-instituutin kanssa, ja saimme liikemittareista saadut datatiedot heiltä. Analysoimme liikemittareiden datatiedot keskimääräisten osuuksien perusteella. Tutkimustuloksemme osoittivat, että lasten liikkuminen ja paikallaanolo muuttuivat iän myötä. Sukupuolten välillä havaittiin myös eroja. Lapset viettivät noin puolet valveillaoloajastaan istuen ja makuuasennossa. Nuoremman ikäluokan lapset olivat aktiivisempia päivän aikana kuin vanhemman ikäluokan lapset. Paikallaan oloa kertyi 3.-luokkaisille vähemmän kuin 5.-luokkalaisille. Pojat viettivät enemmän aikaa paikallaan kuin tytöt, mutta myös liikkuivat reippaasti ja rasittavasti heitä enemmän. Noin puolet lapsista liikkui terveytensä kannalta riittävästi. Liikuntasuositusten toteutumisessa oli suuria eroja ikäryhmien ja sukupuolten välillä. Lasten tulisi liikkua reippaasti ja rasittavasti läpi elämän, ja heidän tulisi täyttää liikuntasuositukset. Tämä pohjautuu reippaan ja rasittavan liikkumisen terveyshyötyihin. Lasten terveydelle on parasta liikkua reippaasti päivittäin ja välttää paikallaanoloa. Passiivisuudella on todettu olevan terveydelle haitallisia tekijöitä.The aim of our thesis was to gather information about 3rd and 5th graders’ physical activity in Lapland and North Ostrobothnia. Our purpose was to study whether children exercise conforming to the physical activity guidelines as to maintain good health. In addition, we researched on how much and with what level of intensity these children moved and how much time they spent sitting and laying down while being awake. The results of our thesis provide information about regional activity habits that can be used in development of children's’ physical activity in those regions. Our thesis was a quantitative study in which the objective research data was collected by using accelerometers. The statistics of children’s daily activities were gathered with the accelerometers during four days. Our study is based on the LIITU 2016 -study. The study was conducted in collaboration with UKK institute in the spring of 2016 and 394 primary schoolers took part in it. After they gave us the data of accelerometers, we analysed results using the mediocre method. Our results indicated that the amount of activity and sedentary behaviour in children changes with age. There were also noticeable differences between genders. Children spent approximately half of their time awake in a sitting position or laying down. The children in the younger age group were less sedentary and they did more physical activities during the day than the children in the older age group. Boys spent more time being sedentary compared to girls but they also did more moderate- and vigorous-intensity activities than girls. About half of the children fulfilled the recommendations of the physical activity guidelines. There were multiple differences in the fulfilment of the physical activity guidelines between ages and genders. The children should fulfil the recommendations of physical activity. The recommendations are based on the positive health effects of moderate- and vigorous-intensity moving. Sedentary behaviour has many negative effects to health and children should reduce being sedentary