Clinical outcomes of PCSK9Is: a meta-analysis of randomized clinical trials

Ghadban, Rugheed; Enezate, Tariq; Omran, Jad; Almourani, Rajaa; Singla, Atul; Balla, Sudarshan

doi:10.21037/cdt.2017.08.16

Cited by 4 publications

(3 citation statements)

References 23 publications

(20 reference statements)

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“…Moreover, an important regression of atheroma plaque volume was observed after 76 weeks of evolocumab treatment in about 2/3 of patients [ 40 ]. The treatment with PCSK9 inhibitors was associated with a lower number of major adverse cardiovascular events, coronary revascularization, and myocardial infarction, but had no effect on mortality [ 94 ]. A highly durable RNA interference therapeutic inhibitor of PCSK9 synthesis is being tested.…”

Section: Discussionmentioning

confidence: 99%

“…A large meta-analysis that included 62,776 patients from 6 randomized clinical trials found that treatment with PCSK9 inhibitors was associated with a lower number of major adverse cardiovascular events, coronary revascularization, and myocardial infarction, but had no effect on mortality. These are arguments for their use in patients with a high risk of ischemic heart disease [ 94 ]. A highly durable RNA interference therapeutic inhibitor of PCSK9 synthesis is being tested.…”

Section: Therapeutic Aspectsmentioning

confidence: 99%

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Pragmatic Analysis of Dyslipidemia Involvement in Coronary Artery Disease: A Narrative Review

Mihăilă

2020

CCR

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Background: Dyslipidemia is the main factor involved in the occurrence and progression of coronary artery disease. Objective: The research strategy is aimed at analyzing new data on the pathophysiology of dyslipidemia involvement in coronary artery disease, the modalities of atherogenic risk estimation and therapeutic advances. Method: Scientific articles published in PubMed from January 2017 to February 2018 were searched using the terms "dyslipidemia" and "ischemic heart disease". Results: PCSK9 contributes to the increase in serum levels of low-density lipoprotein-cholesterol and lipoprotein (a). The inflammation is involved in the progression of hyperlipidemia and atherosclerosis. Hypercholesterolemia changes the global cardiac gene expression profile and is thus involved in the increase of oxidative stress, mitochondrial dysfunction, and apoptosis initiated by inflammation. Coronary artery calcifications may estimate the risk of coronary events. The cardioankle vascular index evaluates the arterial stiffness and correlates with subclinical coronary atherosclerosis. The carotid plaque score is superior to carotid intima-media thickness for risk stratification in patients with familial hypercholesterolemia and both can independently predict coronary artery disease. The lipoprotein (a) and familial hypercholesterolemia have a synergistic role in predicting the risk of early onset and severity of coronary atherosclerosis. A decrease in atherosclerotic coronary plaque progression can be achieved in patients with plasma LDL-cholesterol levels below 70 mg/dL. A highly durable RNA interference therapeutic inhibitor of PCSK9 synthesis could be a future solution. Conclusion: The prophylaxis and treatment of coronary artery disease in a dyslipidemic patient should be based on a careful assessment of cardio-vascular risk factors and individual metabolic particularities, so it may be personalized.

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Section: Discussionmentioning

confidence: 99%

Section: Therapeutic Aspectsmentioning

confidence: 99%

Pragmatic Analysis of Dyslipidemia Involvement in Coronary Artery Disease: A Narrative Review

Mihăilă

2020

CCR

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“…Though statins are effective in reducing adverse cardiovascular outcomes, the need to address substantial residual cardiovascular disease risk among statin-treated individuals has led to the development of new injectable pharmacotherapies such as proprotein convertase subtilisin/kexin type 9 (PCSK9) or angiopoietin like 3 (ANGPTL3) modulating drugs (5,6). There is strong evidence that these agents are clinically effective (7), but they are currently not considered cost effective due to their high price tag and the high prevalence of cardiovascular disease secondary to hyperlipidemia-and hence eligibility for lipid-reducing therapy in the US population. (8) Thus, there exists a pressing need for new drugs to prevent ASCVD, especially if new drugs could be discovered more economically or targeted to new patient subsets (9,10).…”

Section: Introductionmentioning

confidence: 99%

Repurposing the atypical antidepressant trazodone for atherosclerotic cardiovascular disease

Johnson¹,

Narula²,

Glicksberg³

et al. 2021

Preprint

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Background. Current lipid-lowering drugs often leave significant residual risk for adverse outcomes. Identification of previously approved drugs for new indications, drug repurposing, may provide a cost effective alternative to de novo drug developing.Objectives. We combined clinical, transcriptomic, computational, and experimental strategies to explore lipid-lowering and plaque-stabilizing effects of atypical antidepressant trazodone.Methods. First, a connectivity mapping strategy was used to match rosuvastatin gene expression signature derived from a clinical trial of 85 patients with to the expression patterns of 1,309 different small molecules to discover a similarity between the rosuvastatin and trazodone gene expression signatures. Then, we assessed the lipid-lowering ability of trazodone in vitro using HepG2 cells and in vivo using molecular imaging of rabbit atherosclerotic lesions. In addition, we analyzed electronic medical records of patients from three large medical centers who had a prescription for trazodone and lipid laboratory measurements available.Results. Trazodone significantly reduced cholesterol levels in the HepG2 human hepatocyte model, decreased atherosclerotic plaque burden in a rabbit model and lowered low-density lipoprotein (LDL) cholesterol levels in patients.Conclusion. Our results indicate that trazodone may be a promising candidate for adjunctive lipid lowering therapy. It may provide significant benefits to patients with hyperlipidemia, including lipid level reduction and formation of a more favorable atherosclerotic plaque morphology. Patients diagnosed with major depressive disorder requiring better lipid control would benefit the most from the for adjunctive lipid lowering therapy.

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Diabetes and Cardiovascular Disease: an Update

et al. 2019

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Clinical outcomes of PCSK9Is: a meta-analysis of randomized clinical trials

Abstract: PCSK9Is should be strongly considered to improve clinical outcomes in patients at high risk for atherosclerotic CVD.

Cited by 4 publications

References 23 publications

Pragmatic Analysis of Dyslipidemia Involvement in Coronary Artery Disease: A Narrative Review

Pragmatic Analysis of Dyslipidemia Involvement in Coronary Artery Disease: A Narrative Review

Repurposing the atypical antidepressant trazodone for atherosclerotic cardiovascular disease

Diabetes and Cardiovascular Disease: an Update

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