Page 15 - Delaware Medical Journal August 2015
P. 15
SCIENTIFIC ARTICLE
Below we discuss our experiences with lomitapide and mipomersen in clinical practice. We present two patients who have been initiated on these medications, their responses to them and the potential safety issues that have arisen. Finally, we present the clinical trial data for each agent and make recommendations for the appropriate use and surveillance of patients on these agents.
CASE DESCRIPTIONS
Patient A is a 41-year-old male and patient B is a 64-year-old female. Both patients have a past medical history of homozygous familial hypercholesterolemia and were unable to reach target LDL goals on maximum standard lipid lowering therapy. In order to improve their lipid management and further reduce cardiovascular risk, patient A was initiated on lomitapide and patient B was started on mipomersen.
The patient was diagnosed with familial hypercholesterolemia at 4 years of age and, following failure of dietary therapy, began LDL apheresis at age 7. He initially was receiving weekly LDL venous access he was transitioned to receiving plasmapheresis every two weeks.
The patient has a history of multi-vessel coronary artery disease with a myocardial infarction at 28 years of age, percutaneous coronary interventions at 25 and 28 years, and a three-vessel coronary artery bypass graft in April 2011 at 39 years. He also stenosis of his left common carotid artery and 50 to 69 percent stenosis of his right common carotid artery.
The patient’s current medications include aspirin 81 mg twice daily, Rosuvastatin 20 mg twice daily, Clopidogrel 75 mg daily, Lovaza (Omega-3-acid ethyl esters) 1 g twice daily, Metoprolol 25 mg twice daily, Folic Acid 1 mg daily, Iron 325 mg twice daily, Amlodipine 5 mg twice daily, Niacin 500 mg twice daily and a multivitamin daily.
He is married with no children. He has never smoked and drinks alcohol occasionally.
On examination the patient does not have evidence of corneal arcus, xanthelasmas, or tendon xanthomas. He has bilateral carotid bruits and no evidence of aortic stenosis.
FIGURE 1
The patient’s lipid panels are
performed prior to and upon
completion of each plasmapheresis
session. Prior to beginning
lomitapide therapy, while on the
above stated lipid lowering regimen,
results of his pre-plasmapheresis lipid
8, 2013 were as follows: TC 550 mg/dL; HDL-C 45
mg/dL; LDL-C 479 mg/dL; ALT 25 mg/dL; AST 20 mg/dL; Total Bilirubin 0.9 mg/dL; and Alkaline Phosphatase 68 mg/ dL. He was initially started on lomitapide 5 mg daily on April 1, 2013. This dose was temporarily discontinued on April 8, 2013, due to concerns of a potential adverse effect. It was eventually determined that lomitapide was not responsible for patient’s symptoms and the dose was restarted on May 15, 2013, which increased to 20 mg daily on July 12, 2013.
Patient A – Lipid Panel on Lomitapide Therapy.
Following initiation of lomitapide therapy there was a steady, dose dependent reduction in TC, LDL-C and apo B (Figure 1). On July 17, 2014, following almost 18 months of lomitapide therapy and discontinuation of apheresis his lab results were as follows: TC 154 mg/dL; HDL-C 36 mg/dL; LDL-C 111 mg/dL; ALT 71 mg/dL; AST 51 mg/dL; Direct Bilirubin 1.0 mg/dL; and Alkaline Phosphatase 38 mg/dL. Over this time frame there was a decrease in LDL-C by 76.83 percent, TC by 72.0 percent, and apo B by 76.79 percent.
At the initiation of lomitapide the patient’s hepatic function
eight weeks of treatment and then began to steadily increase
to a peak on August, 22, 2013, with an AST 87 mg/dL; ALT 140 mg/dL; ALP 47 mg/dL; and total bilirubin 0.7 mg/dL (Figure 2). These levels then trended back down towards their baseline
and remained below three times the upper limit of normal.
Del Med J | August 2015 | Vol. 87 | No. 8
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