EFFICACY AND SAFETY OF INCLISIRAN BY BASELINE BODY MASS INDEX: A POST HOC POOLED ANALYSIS OF THE ORION-9, ORION-10 AND ORION-11 PHASE III RANDOMIZED CONTROLLED TRIALS

Therapeutic Area: ASCVD/CVD Risk Factors Background: Excessive bodyweight, often associated with dyslipidemia, may affect the pharmacology of drugs. Inclisiran, a small interfering RNA targeting PCSK9 hepatic mRNA, is an effective LDL-C lowering agent with twice-yearly subcutaneous dosing (after the...

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Main Authors: Lawrence A Leiter (Author), David G Kallend (Author), Wolfgang Koenig (Author), Ulf Landmesser (Author), Kausik K Ray (Author), Gregory G Schwartz (Author), R Scott Wright (Author), YannTong Chiang (Author), Lorena Garcia Conde Orozco (Author), Frederick J Raal (Author)
Format: Book
Published: Elsevier, 2023-03-01T00:00:00Z.
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100 1 0 |a Lawrence A Leiter  |e author 
700 1 0 |a David G Kallend  |e author 
700 1 0 |a Wolfgang Koenig  |e author 
700 1 0 |a Ulf Landmesser  |e author 
700 1 0 |a Kausik K Ray  |e author 
700 1 0 |a Gregory G Schwartz  |e author 
700 1 0 |a R Scott Wright  |e author 
700 1 0 |a YannTong Chiang  |e author 
700 1 0 |a Lorena Garcia Conde Orozco  |e author 
700 1 0 |a Frederick J Raal  |e author 
245 0 0 |a EFFICACY AND SAFETY OF INCLISIRAN BY BASELINE BODY MASS INDEX: A POST HOC POOLED ANALYSIS OF THE ORION-9, ORION-10 AND ORION-11 PHASE III RANDOMIZED CONTROLLED TRIALS 
260 |b Elsevier,   |c 2023-03-01T00:00:00Z. 
500 |a 2666-6677 
500 |a 10.1016/j.ajpc.2022.100403 
520 |a Therapeutic Area: ASCVD/CVD Risk Factors Background: Excessive bodyweight, often associated with dyslipidemia, may affect the pharmacology of drugs. Inclisiran, a small interfering RNA targeting PCSK9 hepatic mRNA, is an effective LDL-C lowering agent with twice-yearly subcutaneous dosing (after the initial and 3-month doses). The aim of this analysis was to assess the efficacy and safety of inclisiran in patients with heterozygous familial hypercholesterolemia, atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk equivalent across body mass index (BMI) strata. Methods: In this post hoc analysis from ORION-9 (NCT03397121), ORION-10 (NCT03399370) and ORION-11 (NCT03400800), eligible patients were randomized 1:1 to receive 300 mg inclisiran sodium (equivalent to 284 mg inclisiran) or placebo at baseline, Day 90 and 6-monthly thereafter. Analysis was stratified by baseline BMI: <25, 25-<30, 30-<35 or ≥35 kg/m2. Percentage change in atherogenic lipids from baseline at Day 510 was evaluated. Safety was assessed over 540 days. Results: Baseline demographic and clinical characteristics including atherogenic lipid levels were mostly balanced between treatment arms and across BMI strata (Table). Percentage change in atherogenic lipids from baseline at Day 510 was significantly greater with inclisiran vs placebo within each BMI stratum (Table). Treatment-emergent adverse events (TEAE) and treatment-emergent serious adverse events were generally similar between treatment arms and were reported more frequently with increasing BMI strata (data not shown). Clinically relevant TEAEs at the injection site were reported more frequently with inclisiran vs placebo similarly across strata, but all were mild or moderate. Conclusion: Twice-yearly dosing with inclisiran (after the initial and 3-month doses) provided effective and sustained lipid lowering in patients, irrespective of their baseline BMI, and was generally well tolerated. 
546 |a EN 
690 |a Diseases of the circulatory (Cardiovascular) system 
690 |a RC666-701 
690 |a Public aspects of medicine 
690 |a RA1-1270 
655 7 |a article  |2 local 
786 0 |n American Journal of Preventive Cardiology, Vol 13, Iss , Pp 100403- (2023) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S2666667722000873 
787 0 |n https://doaj.org/toc/2666-6677 
856 4 1 |u https://doaj.org/article/0011f94e522840b59e2bf9b7e51e40ab  |z Connect to this object online.