MANAGING SEVERE HYPERCHOLESTEROLEMIA

MANAGING  SEVERE  HYPERCHOLESTEROLEMIA
QUESTION-60 yo Lebanese male with familial hypercholesterolemia but no personal or FH of CAD.
Fasting lipids before any pharmacologic therapy:
-Tchol 380
-HDL 46
-LDL 297
-Trig 184
He has been on statin + gemfibrozil for many years without ill-effect. He was switched to fenofibrate many years ago but could not tolerate, and was put back on gemfibrozil.  Diet and exercise have been emphasized for years, but he travels for work, stays in hotels for weeks at a time, and finds it difficult to comply with lifestyle recommendations.

Recent fasting lipids on Crestor 40 mg + gemfibrozil 600 mg BID:
-Tchol 196
-HDL 52
-LDL 130
-Trig 72
A few weeks ago, Gemfibrozil was stopped, and he was continued just on Crestor 40 mg
Fasting lipids on just Crestor 40 mg:
-TChol 248
-HDL 54
-LDL 169
-Trig 129
Even though he does not have hypertriglyceridemia, the fibrate was helping to keep his LDL down in a more ideal range.  For adults with a baseline  LDL > 190, the ACC/AHA recommends treatment with high-intensity statin and consideration of use of non-statin drugs to further reduce the LDL. However, fibrates are not typically recommended in this circumstance.
My questions are as follows:
1) Would you recommend resuming the Gemfibrozil in combination with Crestor in this patient?
2) Or would you consider an alternative add-on medication such as Zetia or Bile-acid resin?
3) Or would you suggest switching his regimen entirely to a PCSK9 inhibitor, if insurance would approve?
4) Or would you leave him alone with just Crestor monotherapy and the most recent lipid results?
I appreciate the expert advice. Marcy Cheifetz, MD
RESPONSE- Dr. Cheifetz
1)      Would you recommend resuming the Gemfibrozil in combination with Crestor in this patient? Answer: I would avoid gemfibozil treatment for two reasons. First, gemfibrozil is not a very effective drug in lowering LDL cholesterol levels. Second, in combination with most statins there is an increased risk of myositis. Thus, the risk is greater than the potential benefits with gemfibrozil therapy.
2)      Or would you consider an alternative add-on medication such as Zetia or Bile-acid resin?
Answer: Since the patient is taking a maximal dose of the most potent statin and the LDL level is still above my goal (my goal at a minimum would be an LDL < 100mg/dl in your patient) I would initiate combination therapy. I prefer ezetimibe (Zetia) over bile acid binders as they are much easier to take and have fewer potential side effects. An exception would be a patient with diabetes with a slightly elevated A1c level. Bile acid binders lower A1c levels by approximately 0.5% and in some patients this glucose lowering effect is advantageous. If LDL is still above goal on combination therapy one could consider adding a third drug.
3)      Or would you suggest switching his regimen entirely to a PCSK9 inhibitor, if insurance would approve?
Answer: PCSK9 inhibitors are indicated in patients on maximally tolerated statin therapy with either familial hypercholesterolemia or atherosclerotic cardiovascular disease with LDL levels not at goal. Thus in your patient who is tolerating Crestor 40mg daily one would add a PCSK9 inhibitor in combination with the statin. Some insurance companies are requiring patients to be on both maximally tolerated statin and ezetimibe before initiating PCSK9 inhibitor therapy due to the high cost of these monoclonal antibodies. I would first try ezetimibe and if LDL is not in acceptable range I would then add a PCSK9 monoclonal antibody.
4)      Or would you leave him alone with just Crestor monotherapy and the most recent lipid results?

Answer: I would not be satisfied with an LDL of 169mg/dl and therefore would add additional therapy to further lower LDL.
Additional opinion- I would obtain a cardiac CT to determine the coronary calcium score. This would provide an index of the degree of atherosclerosis and help determine how aggressive one needs to be in lowering LDL levels. For example if your patient had a coronary artery calcium score of 400 I would be very aggressive in lowering LDL levels and my goal would be less than 70mg/l. In contrast, if the coronary calcium score was 0 (unlikely) I would be just treat with the combination of Crestor 40mg and ezetimibe 10mg daily.
I hope this answers your questions and is helpful. If not do not hesitate to let us know.
Kenneth Feingold, MD