Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors: Ready to Target Atherosclerotic Cardiovascular Disease beyond Statins

2017 ◽  
Vol 3 (3) ◽  
pp. 147-153
Author(s):  
Nidhi Mishra ◽  
Prabhash C Manoria
Author(s):  
Daniel M. Blumenthal ◽  
Thomas M. Maddox ◽  
Krishna Aragam ◽  
Chana A. Sacks ◽  
Salim S. Virani ◽  
...  

Background: Little is known about patterns of PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitor) use among patients with established clinical atherosclerotic cardiovascular disease. This study’s objective was to describe PCSK9i prescribing patterns among patients with atherosclerotic cardiovascular disease. Methods: We used a national outpatient clinic registry linked to zip-code level on household income from the US Census to assess characteristics of patients with atherosclerotic cardiovascular disease and LDL-C (low-density lipoprotein cholesterol) <190 mg/dL between September 1, 2015, and September 30, 2019, who did and did not receive PCSK9i prescriptions and practice-level and temporal variation in PCSK9i prescriptions. We assessed predictors of PCSK9i prescription with a multivariable mixed effects regression model which included patient covariates as fixed effects and the cardiology practice as a random effect. Adjusted practice-level variation in PCSK9i prescribing was evaluated with median odds ratio (OR). Results: Of 2 148 100 patients meeting study inclusion criteria, 27 249 (1.3%) received PCSK9i prescriptions. Receiving a PCSK9i prescription was associated with White race (versus non-White: OR, 1.78 [95% CI, 1.55–1.83]); high estimated household income (versus low income: OR, 1.18 [95% CI, 1.08–1.29]), and urban or suburban (versus rural) practice location (urban: OR, 1.47 [95% CI, 1.32–1.64]; suburban: OR, 1.25 [95% CI, 1.13–1.39]). Hispanics had lower odds of receiving PCSK9i prescriptions (OR, 0.66 [95% CI, 0.57–0.76]). The adjusted median odds ratio was 2.68 (95% CI, 2.46–2.94), consistent with clinically significant practice-level variation in PCSK9i prescriptions. No differences in quarterly PCSK9i prescription rates were observed before and after price reductions for evolocumab and alirocumab initiated during the fourth quarter of 2018 and first quarter of 2019, respectively. Conclusions: This study highlights racial, socioeconomic, geographic, and practice-level variations in early PCSK9i prescriptions which persist despite adjustment for clinical and demographic factors. After adjustment, 2 randomly selected practices would differ in likelihood of PCSK9i prescription by a factor of >2.


2018 ◽  
Vol 25 (13) ◽  
pp. 1480-1500 ◽  
Author(s):  
Sho-ichi Yamagishi ◽  
Takanori Matsui

Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors, serpins. It was first identified as a neuronal differentiating factor secreted by human retinal pigment epithelial cells, and then found to be the most potent inhibitor of pathological angiogenesis in mammalian eyes. Recently, PEDF has been shown not only to suppress oxidative stress and inflammatory reactions in vascular wall cells, T cells and macrophages, and adipocytes, but also to exert antithrombotic and anti-fibrotic properties, thereby protecting against the development and progression of various cardiometabolic diseases and related complications. Furthermore, accumulating evidence has suggested that circulating PEDF levels may be a biomarker of severity and prognosis of these devastating disorders. Number of subjects with visceral obesity and insulin resistance is increasing, and the metabolic syndrome and its related complications, such as diabetes, nonalcoholic fatty liver disease/non-alcoholic steatohepatits, and atherosclerotic cardiovascular disease are a growing health challenge. Therefore, in this study, we review the pathophysiological role of PEDF in obesity and metabolic disorders, cardiovascular disease, diabetic eye and kidney complications, liver diseases, and reproductive system disorders, and discuss the potential clinical utility of modulating the expression and actions of PEDF for preventing these cardiometabolic disorders. We also refer to the clinical value of PEDF as a biomarker in cardiometabolic complications.


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