1.
Vaccines Targeting PCSK9: A Promising Alternative to Passive Immunization with Monoclonal Antibodies in the Management of Hyperlipidaemia?
Weisshaar, S, Zeitlinger, M
Drugs. 2018;(8):799-808
Abstract
Hypercholesterolaemia is frequently observed in patients with cardiovascular diseases (CVD) and is associated with increased mortality. Statin treatment has been the standard of care for reducing low-density lipoprotein cholesterol (LDL-C) to improve cardiovascular outcomes. However, statins have limited effects in some patients and may be discontinued due to adverse effects resulting in LDL-C above target levels. The proprotein convertase subtilisin kexin type 9 (PCSK9) is a pivotal regulator in the LDL-C metabolism by degrading the LDL-C receptor on hepatocytes. Inhibition of PCSK9 by monoclonal antibodies (mAb) significantly lowers LDL-C levels and is considered to reduce the likelihood of adverse cardiac events. However, such treatment regimens are not cost-effective, and require frequent administrations at high doses that may be associated with side effects and poor drug adherence. Furthermore, it has been shown that these PCSK9 medicines may trigger the formation of antidrug antibodies followed by a significant attenuation of the LDL-C-lowering effect. Active vaccination inducing high-affinity antibodies against PCSK9 with less frequent administration intervals may be a novel promising therapeutic approach to overcome the drawback of passive immunization with PCSK9 mAb. However there is a paucity of available clinical safety and efficacy data. This article discusses challenges in the development of PCSK9 vaccines and their potential therapeutic benefits by reviewing clinical studies that evaluated the safety and efficacy of PCSK9 mAb.
2.
Inhibitory effects of micronized fenofibrate on carotid atherosclerosis in patients with essential hypertension.
Zhu, S, Su, G, Meng, QH
Clinical chemistry. 2006;(11):2036-42
Abstract
BACKGROUND The coexistence of hypertension and dyslipidemia synergistically increases the risk of cardiovascular events. We investigated the effect of the lipid-lowering agent micronized fenofibrate on inhibition of carotid atherosclerosis in patients with essential hypertension and mild hyperlipidemia. METHODS We measured serum lipid profiles and inflammatory markers on chemistry or immune analyzers and common or internal carotid intima-media thickness (IMT) and diameter (D) by ultrasonography. RESULTS Patients receiving micronized fenofibrate for 24 months in addition to antihypertensive treatment had decreased concentrations of total cholesterol, LDL-cholesterol, triglyceride, apolipoprotein B100, oxidized LDL, high-sensitivity C-reactive protein, P-selectin, and cytokines. These patients had increased concentrations of HDL-cholesterol, apolipoprotein A-I, and nitric oxide. Common carotid artery IMT (CCAIMT) and internal carotid artery IMT (ICAIMT) remained unchanged during the 24-month intervention. Moreover, the mean CCAIMT/D ratio and ICAIMT/D ratio were significantly decreased in the fenofibrate intervention group. In contrast, CCAIMT/D and ICAIMT/D ratios were increased in the control group. The incidence rates of carotid artery plaque formation and stroke in the fenofibrate intervention group were significantly lower than those in the control group. CONCLUSION The combination of antihypertensive agents with micronized fenofibrate can effectively prevent the progression of carotid atherosclerosis and reduce the incidence of stroke in patients with essential hypertension.