<p>Safety and Tolerability of PCSK9 Inhibitors: Current Insights</p>

Abstract

The current era of preventive cardiology continues to emphasize on low-density lipoprotein cholesterol (LDL-C) reduction to alleviate the burden of atherosclerotic cardiovascular disease (ASCVD). In this regard, the pharmacological inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme via monoclonal antibodies has emerged as a novel lipid-lowering therapy, leading to a marked reduction in circulating LDL-C levels and subsequent improvement of cardiovascular outcomes. As these agents are increasingly used in current clinical practice, mounting scientific and clinical evidence supports that PCSK9 inhibitors offer an excellent safety and tolerability profile with a low incidence of adverse events. Notably, the most frequently reported side effects are injection-site reactions. In contrast to statins, PCSK9 inhibitors do not appear to exert a detrimental effect on glycemic control or to increase the incidence of new-onset diabetes mellitus. Accumulating evidence also indicates that PCSK9 inhibitors are a safe, well-tolerated and effective therapeutic strategy for patients with statin intolerance. On the other hand, as PCSK9 inhibitors reduce LDL-C to unprecedented low levels, a large body of current research has examined the effects of their long-term administration on neurocognition and on levels of vitamin E and other fat-soluble vitamins, providing encouraging results. This review aims to present and discuss the current clinical and scientific evidence pertaining to the safety and tolerability of PCSK9 inhibitors.

Prevalence of atherosclerotic cardiovascular disease and subsequent major adverse cardiovascular events in Alberta, Canada: A real‐world evidence study

“…Finally, this study should be interpreted in the context of sev- Upon the publication of the 2016 guidelines, ezetimibe and PCSK9is were newly included in the Canadian treatment guidelines as add-ons to statin therapy to get patients below LDL-C goal. The introduction, uptake, and potential benefits of adjunctive ezetimibe and PCSK9i, 34,35 would not be captured in this study, even though they are now more widely used. While temporal treatment patterns were not the objective of this study, treatment outcomes from an Alberta-based sample were evaluated in our previous publication and could be expanded upon in future studies.…”

New and emerging lipid-modifying drugs to lower LDL cholesterol

“… 30 Common adverse effects of PCSK9 inhibitors are usually mild and include nasopharyngitis, injection-site reactions and upper respiratory tract infections. 31 , 32 …”

“…The initial cost of PCSK9 inhibitors (US$14,100 per annum in the United States until October 2018) was very steep, far exceeding the costs of other lipid-lowering medications. 31 , 92 However, in October 2018 and February 2019, respectively, the main PCSK9 inhibitor manufacturing companies reduced the cost of PCSK9 inhibitors by 60%, to US$5850 per annum, thus greatly improving cost-effectiveness and making these agents more easily accessible in clinical practice. 31 …”

“… 31 , 92 However, in October 2018 and February 2019, respectively, the main PCSK9 inhibitor manufacturing companies reduced the cost of PCSK9 inhibitors by 60%, to US$5850 per annum, thus greatly improving cost-effectiveness and making these agents more easily accessible in clinical practice. 31 …”

Inclisiran—Silencing the Cholesterol, Speaking up the Prognosis

“…PCSK9i also have multiple pleiotropic effects, including the stabilization of atherosclerotic plaque, antiplatelet effects, antineoplastic effects, and anti-bacterial effects [78]. A positive outcome of the use of PCSK9is resulted in their approval in both the US and Europe for FH patients who are intolerant to statins or at high risk of ASCVD, who require an especially potent LDL-C-lowering treatment [79].…”