Table 2.
Summary of indications, contraindications, and main side effects of the novel Lipid Lowering agents.
| Drugs | Indication | Contraindications | Side Effects |
|---|---|---|---|
| PCSK9-i | Adults with primary hyperlipidemia (including HeFH) as an adjunct to diet, alone or in combination with other lipid-lowering therapies; In patients with HoFH as an adjunct to diet and other LDL-lowering therapies (e.g., statins, ezetimibe, LDL apheresis) |
Patients with a history of a serious hypersensitivity reaction to PCSK9-i | Nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions [20,21] |
| Bempedoic Acid | Adults with HeFH or established ASCVD who require additional lowering of LDL-C as an adjunct to diet and maximally tolerated statin therapy | None | Upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia and elevated liver enzymes [33] |
| Inclisiran | Adults with HeFH or ASCVD, who require additional lowering of LDL-C as an adjunct to diet and maximally tolerated statin therapy | None | Injection site reaction, arthralgia, urinary tract infection, diarrhea, bronchitis, pain in extremity, and dyspnea [45,46,47] |
| LXR agonists | Not yet approved | No human trials available | No human trials available |
| PPARs β/δ agonists | Not yet approved | No human trials available | No human trials available |
| ANGPTL3 inhibitors | Adult and pediatric patients, aged 12 years and older, with HoFH as an adjunct to other LDL-C lowering therapies | History of serious hypersensitivity reactions to ANGPTL3 inhibitors | Nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, and nausea [85,86] |
| Mipomersen | In patients with HoFH as an adjunct to lipid-lowering medications and diet to reduce LDL-C, ApoB, TC, and non HDL-C | Moderate or severe hepatic impairment, or active liver disease, including unexplained persistent elevations of serum transaminases; Known sensitivity to product components |
Injection site reactions, flu-like symptoms, nausea, headache, and elevations in serum transaminases, specifically ALT [87,96] |
| Lomitapide | In patients with HoFH to reduce LDL-C, TC, apo B, and non-HDL-C as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis | Pregnancy, concomitant use with strong or moderate CYP3A4 inhibitors, moderate or severe hepatic impairment or active liver disease including unexplained persistent abnormal liver function tests | Diarrhea, nausea, vomiting, dyspepsia, and abdominal pain [103,104,108] |
| Volanesorsen | In adult patients with genetically confirmed FCS and at high risk for pancreatitis, in whom response to diet and triglyceride lowering therapy has been inadequate | Hypersensitivity to the drug; Chronic or unexplained thrombocytopenia. Treatment should not be initiated in patients with platelet count < 1.40 × 1011/L |
Injection site reactions, serum sickness, and thrombocytopenia [110] |
ANGPTL3: angiopoietin-like proteins; ALT: Alanine-Aminotransferase; ApoB: Apolipoprotein B; ASCVD: Atherosclerotic Cardiovascular Disease; CYP3A4: cytochrome P450 3A4; FCS: Familial Chylomicronemia Syndrome; HDL-C: high density lipoprotein cholesterol; HoFH: homozygous familial hypercholesterolemia; LDL-C: low density lipoprotein cholesterol; LXR: Liver X Receptors; PCSK9: proprotein convertase subtilisin/kexin type 9; PPAR: peroxisome proliferator activated receptors; TC: total cholesterol.