|Patient's Actual||ACC Suggested|
|% LDL-C Reduction from pretreatment||30-49%|
|Current LDL-C ()|
|Non HDL-C ()||~|
10 mg PO daily, with or without food. Take either > 2 hours before or ≥ 4 hours after BAS if used in combination.
Monotherapy-18%; combination therapy with statin (incremental reduction)-25%
Monotherapy—upper respiratory tract infection, diarrhea, arthralgia, sinusitis, pain in extremity; combination with statin— nasopharyngitis, myalgia, upper respiratory tract infection, arthralgia, diarrhea.
cyclosporine, fibrates, BAS
Generally well tolerated. Generic available.
1) Colesevelam: Tablets: 6 tablets PO once daily or 3 tablets PO twice daily; take tablets with a meal and liquid. Suspension: one 3.75-gram packet PO daily, or one 1.875-gram packet PO twice daily; mixed powder with 4–8 ounces of water, fruit juice, or soft drink; take with meal. 3.75 g is equivalent to 6 tablets. 1.875 g is equivalent to 3 tablets
2) Cholestyramine: 8–16 g/day orally divided into 2 doses
3) Colestipol: 2 to 16 g/day orally given once or in divided doses
Colesevelam: Monotherapy-15% (6 tablets daily); combination with low- to moderate intensity statin-additional 10-16% reduction in LDL-C (data from simvastatin 10 mg, atorvastatin 10 mg).
Cholestyramine: Monotherapy-10.4% vs placebo. Colestipol: not provided in PI. In dose-ranging RCT with monotherapy, doses of 5 g, 10 g, and 15 g resulted in 16.3%, 22.8%, and 27.2% reduction in LDL-C, respectively. (Superko HR, Greenland P, Manchester RA, et al. Am J Cardiol. 1992;70:135-40.)
Constipation, dyspepsia, and nausea. Post-marketing reports with colesevelam include ↑ seizure activity or ↓ phenytoin levels in patients receiving phenytoin, ↓ INR in patients receiving warfarin, ↑ TSH in patients receiving thyroid hormone replacement therapy, bowel obstruction, dysphagia, esophageal obstruction, fecal impaction, hypertriglyceridemia, pancreatitis, and increased transaminases.
cyclosporine, glimepiride, glipizide, levothyroxine, olmesartan coadministered with medoxomil, oral contraceptives containing ethinyl estradiol and norethindrone, phenytoin, warfarin. Drugs with potential interaction should be taken at least 4 hours after BAS to avoid impeding their absorption.
Pill burden; inconvenience in preparation of oral suspension preparations; GI side effects; exacerbation of hypertriglyceridemia; orally administered, colesevelam lowers HbA1c 0.5% in diabetes; CV outcomes data not available.
Food source must be low in saturated fat and cholesterol, and include one or more of the following whole oat or barley foods: 1) oat bran, 2) rolled oats, 3) whole oat flour, 4) whole grain barley or dry milled barley.
With intake of 3.0-12.4 g/day, mean TC and LDL-C levels were ↓ relative to control by 9.7 and 11.6 mg/dL, respectively.
Few safety concerns. If viscous fiber supplements such as fiber laxatives are used, it is critical to consume adequate fluid as directed on the product label to avoid intestinal blockage (a rare occurrence).
Reduced carotenoid absorption. Regular consumption of fruits and vegetables should help to counteract this potential effect.
1-3 g PO per day consumed with meals either once daily or in divided doses
Consumption of 2 g/day of phytosterols ↓ LDL-C by 5-15%. LDL-C ↓ plateaus at doses above ~3 g/day.
Phytosterol esters have "generally recognized as safe" (GRAS) status in the US. Potential safety concern regarding phytosterol consumption in patients with phytosterolemia. Side effects may include mild bloating, diarrhea, or constipation.
BAS administration should be separated from phytosterol use by 2-4 hours to avoid binding of the latter in the gut.
Generally well tolerated; modest ↓ in LDL-C; CV outcomes data not available.
Alirocumab—initiate 75 mg subcutaneously (SQ) every 2 weeks. If more LDL reduction needed, may ↑ dose to 150 mg every 2 weeks. Alternative starting dose is 300 mg SQ every 4 weeks.
Evolocumab—in primary hypercholesterolemia with established clinical ASCVD or HeFH, give 140 mg SQ every 2 weeks or 420 mg SQ once monthly in abdomen, thigh, or upper arm. In HoFH, give 420 mg SQ once monthly. To administer 420 mg, give 3 (140 mg) injections consecutively within 30 minutes.
Alirocumab—when added to maximally tolerated statin therapy, alirocumab 75 mg and 150 SQ every 2 weeks ↓ LDL-C by an additional 43% and 47%, respectively. When added to maximally tolerated statin therapy evolocumab 140 mg every 2 weeks and 420 mg SQ every 4 weeks, ↓ LDL-C by an additional 64% and 58%, respectively.
Alirocumab—nasopharyngitis, injection site reactions, influenza.
Evolocumab—nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions. No evidence of increase in cognitive adverse effects observed in FOURIER or EBBINGHAUS.
No clinically significant drug-drug interactions identified for alirocumab or evolocumab.
Cost, SQ administration, robust LDL-C reduction, CV outcomes trials not completed for alirocumab, burdensome prior authorization process.
Consider referring patients with baseline LDL-C ≥190 mg/dL, very high risk for ASCVD, complex lipid disorders, statin intolerance or multiple lipid medication intolerances, or familial hypercholesterolemia for consultation with a lipid specialist for advanced management.
Lipid specialists may not be easily available in some rural or remote locations.
Initiate 5 mg PO once daily. Titrate dose based on acceptable safety/tolerability: increase to 10 mg daily after at least 2 weeks and then, at a minimum of 4-week intervals, to 20 mg, 40 mg, and up to maximum recommended dose of 60 mg daily.
Mean and median percent changes in LDL-C from baseline when added to baseline lipid-lowering therapy were -40% and -50%, respectively.
Diarrhea, nausea, vomiting, dyspepsia, and abdominal pain. Increases hepatic fat (hepatic steatosis) with or without concomitant increases in transaminases. Hepatic steatosis associated with lomitapide may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis.
CYP3A4 inhibitors increase exposure to lomitapide. Strong and moderate CYP3A4 inhibitors are contraindicated with lomitapide. Avoid grapefruit juice. Do not exceed 30 mg daily of lomitapide when used concomitantly with weak CYP3A4 inhibitors, including atorvastatin and oral contraceptives. Increases plasma concentrations of warfarin; monitor INR regularly, especially with lomitapide dose adjustment. Increased systemic exposure to simvastatin and lovastatin exposure with lomitapide. Limit statin dose when co-administered due to myopathy risk. Consider dose reduction of P-gp substrate because of possible increased absorption with lomitapide. Separate lomitapide dosing with BAS by at least 4 hours. Because of the risk of hepatotoxicity, lomitapide available only through REMS program.
Cost, oral administration, requires strict adherence to low-fat diet and gradual dose escalation to reduce GI side effects, requires monitoring of transaminase levels, long-term consequences of hepatic steatosis unknown, prescriber training, REMS program
200 mg SQ once weekly
Response to addition of mipomersen to maximally tolerated lipid-lowering medication in patients with HoFH—25%.
Injection site reactions, flu-like symptoms, nausea, headache and elevations in serum transaminases, specifically ALT. Increases hepatic fat (hepatic steatosis) with or without concomitant increases in transaminases. May be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis. Because of the risk of hepatotoxicity, mipomersen is available only through REMS program
No clinically relevant pharmacokinetic interactions were reported between mipomersen and warfarin, simvastatin, or ezetimibe.
Cost, SQ administration, requires monitoring of transaminase levels, long-term consequences of hepatic steatosis unknown, prescriber training, REMS program
Extracorporeal technique performed weekly or biweekly.
With weekly or biweekly treatment, average LDL-C can ↓ to ~50–60% of the original levels. LDL-C increases after each apheresis session but does not return to the original level
Problems with venous access; transient hypotension, fatigue; bleeding; hypocalcemia; iron deficiency due to regular phlebotomy for diagnostic purposes; heparin allergy; and bradykinin syndrome (especially with ACEI).
ACEI should not be used with dextran sulfate method owing to risk of bradykinin syndrome.
Cost, extracorporeal technique, inconvenient, locations not readily available in some regions, time-consuming, robust reduction in LDL-C.
|With Genetic Testing Performed|
|apoB indicates apolipoprotein B; CAD, coronary artery disease; FH, familial hypercholesterolemia; ICD-10, International Classification of Disease, 10th Revision; LDL, low-density lipoprotein; LDL-C, low-density lipoprotein cholesterol; and PCSK9, proprotein convertase subtilisin/kexin 9.|
|*Gidding SS, Champagne MA, de Ferranti SD, et al. The agenda for familial hypercholesterolemia: a scientific statement from the American Heart Association. Circulation. 2015;132:2167–92.|
This version of the application has been
locked because of need to ugrade the science.
Please go to the store upgrade this application.