Chronically elevated low-density lipoprotein (LDL) has harmful effects on the vasculature including increased vasoconstriction and the formation of plaques which may rupture, causing coronary heart disease and stroke. In patients with familial hypercholesterolemia, adequate reduction of LDL is especially challenging. Although HMG-CoA reductase inhibitors (statins) are the mainstays for LDL lowering, other treatments such as proprotein convertase subtilisin/kexin type 9 inhibitors, bempedoic acid, incliseran, lomitapide, and apheresis have been employed in an effort to achieve adequate LDL reduction in these patients. Despite these available therapies, many patients with familial hypercholesterolemia do not meet the LDL targets suggested in current guidelines. Evinacumab is a novel lipid-lowering therapy that exerts its LDL-lowering effect through inhibition of angiopoietin-like protein 3 (ANGPTL3). ANGPTL3 inhibits the breakdown of triglyceriderich lipoproteins, such as very low-density lipoprotein and chylomicrons. By inhibiting ANGPTL3, evinacumab allows these lipoproteins to be degraded, ultimately leading to reductions in LDL, high-density lipoprotein, and triglycerides. Clinical trials have demonstrated evinacumab to be safe and effective in reducing LDL. However, data are lacking regarding its potential to reduce risk of atherosclerotic cardiovascular disease. Evinacumab is generally well tolerated with the primary adverse effects comprising infusion reactions, nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, and nausea. While evinacumab is an interesting therapy, until it is proven to reduce cardiovascular events, its high cost leaves its anticipated role in therapy somewhat ambiguous. In the meantime, it may be a useful therapy for those with homozygous familial hypercholesterolemia.
Oral oncolytic treatment options have expanded over the last decade and have brought to light the need to monitor and manage cardiovascular (CV) disease in patients being treated with these therapies. There is a need to assess CV risk before patients receive oral oncolytic therapy with known potential to cause negative CV sequelae such as left ventricular dysfunction, hypercholesterolemia, hypertension, and arrhythmias. The review highlights the need to evaluate traditional CV risk factors and their association with the development and progression of cancer. Additionally, this review suggests approaches to monitor for CV adverse events and manage CV disease during and after treatment with oral oncolytic therapy. Key guideline recommendations are reviewed and highlight specific approaches to minimize CV harm for patients exposed to oral oncolytic therapy. Careful monitoring and patient-centered decision making is key in choosing appropriate therapies. A multidisciplinary approach between oncologists, cardio-oncologists, pharmacists, and other members of the healthcare team is essential in navigating cardiac toxicities.
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