Association between adherence to statin therapy and low-density lipoprotein cholesterol (LDL-c) response in first-time users of standard-dose and low-dose statins: the PharmLines Initiative

Author(s):  
Sylvi Irawati ◽  
Johanna E. Emmens ◽  
Stijn de Vos ◽  
Jens H.J Bos ◽  
Rudolf de Boer ◽  
...  
2019 ◽  
Vol 27 (6) ◽  
pp. 593-603 ◽  
Author(s):  
Christie M Ballantyne ◽  
Ulrich Laufs ◽  
Kausik K Ray ◽  
Lawrence A Leiter ◽  
Harold E Bays ◽  
...  

Aims The aim of this study was to evaluate the low-density lipoprotein cholesterol lowering efficacy and safety of a bempedoic acid 180 mg and ezetimibe 10 mg fixed-dose combination in patients with hypercholesterolemia and a high risk of cardiovascular disease receiving maximally tolerated statin therapy. Methods This phase 3, double-blind clinical trial enrolled adult patients at high risk of cardiovascular disease due to atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or multiple cardiovascular disease risk factors. Patients were randomly assigned (2:2:2:1) to treatment with the fixed-dose combination, bempedoic acid 180 mg, ezetimibe 10 mg or placebo added to stable background statin therapy for 12 weeks. The primary efficacy endpoint was the percentage change from baseline to week 12 in low-density lipoprotein cholesterol. Results Among the 301 patients included in the primary analysis, the mean baseline low-density lipoprotein cholesterol level was 3.87 mmol/L (149.8 mg/dL). At week 12, the fixed-dose combination lowered low-density lipoprotein cholesterol (–36.2%) significantly more than placebo (1.8% (placebo-corrected difference –38.0%); P < 0.001), ezetimibe alone (–23.2%; P < 0.001) or bempedoic acid alone (–17.2%; P < 0.001). The fixed-dose combination lowered low-density lipoprotein cholesterol levels similarly across subgroups, including patients receiving high-intensity, other-intensity or no statin therapy. Improvements with the fixed-dose combination were also observed in secondary efficacy endpoints, including high-sensitivity C-reactive protein. In this trial, fixed-dose combination treatment had a generally similar safety profile compared with bempedoic acid, ezetimibe or placebo. Conclusion The bempedoic acid and ezetimibe fixed-dose combination significantly lowered low-density lipoprotein cholesterol versus placebo or other oral monotherapies and had a favourable safety profile when added to maximally tolerated statin therapy in patients with hypercholesterolemia and high cardiovascular disease risk. Trial Registration ClinicalTrials.gov identifier: NCT03337308.


2019 ◽  
Vol 14 (6) ◽  
pp. 922-934 ◽  
Author(s):  
Yu. A. Karpov

The aim of this review was to present the recently published results of ODYSSEY OUTCOMES trial and discuss the clinical perspective of these data. Patients with acute coronary syndrome are at very high risk of recurrent ischemic cardiovascular complications, especially during the first year after the event. The use of high-intensity statin therapy in this group of patients does not always lead to the achievement of target levels of atherogenic lipoproteins. PCSK9 inhibitors, administered in addition to statins, can provide additional reduction of low-density lipoprotein cholesterol, which leads to further improvements of outcomes in patients with atherosclerotic cardiovascular disease. According to the latest results from ODYSSEY OUTCOMES trial, among patients with recent acute coronary syndrome, who were receiving high-intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower among those who were treated with alirocumab then among those who received placebo. The treatment with alirocumab in patients with recent acute coronary syndrome was associated with reduction in death from any causes. The absolute risk reduction with alirocumab was the most prominent in the subpopulation of patients with low-density lipoprotein cholesterol ≥2,6 mmol/l at baseline. These results have implication for clinical practice and may play an important role for the improvement of outcomes in patients at highest cardiovascular risk after acute cardiovascular syndrome.


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