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3yr
Targeted treatment for familial hypercholesterolemia

Familial hypercholesterolemia (FH) is an autosomal codominant genetic condition, which results in heightened levels of LDL-C in the blood. It is diagnosed by the presence of mutations in low-density lipoprotein receptor (LDLR), apolipoprotein (ApoB), or proprotein convertase subtilisin/kexin 9 (PCSK9), with the LDLR mutation most common. The LDLR variant results in the malfunction of LDLR and problems with the clearance of LDL-C from the blood.



The worldwide mortality rate of FH is between 1:200 and 1:300, and if left untreated, FH can lead to premature atherosclerosis and an elevated risk of cardiovascular events. Because lifestyle modification alone is insufficient to maintain decreased LDL-C concentrations in FH patients, lipid-lowering therapy is necessary. Newer treatment options include small-molecule- or antibody-based approaches.



How do you treat patients with heterozygous FH who need additional lowering of LDL-C levels than that conferred by maximally tolerated statin dosages and lifestyle intervention? How do you determine when and what agents to use based on patient type?


  • 3yr
    make sure that they're on the right statin (atorva or rosuva) at highest dose, then add PCSK9i, then add ezetimibe, then add bempedoic acid...
  • 3yr
    In FH Patients since there is very high risk of the ASCVD at an early age they should be treated as CAD equivalent and the LDL should be than 70 and it is unikley that LDL alone would get to that goal on Statin alone and combination therapy with Ezetemibe and Nexteilol can be started but in practice to achieve the target PCSK-9 inhibitors needs to be started in particualr there is LDR - Mutation .
  • 3yr
    Hands down, I would recommend a PCSK9 inhibitor in addition to maximally tolerated statin and or Ezetimibe, keeping his LDL as low as possible to reduce his CV risk for future CV events
  • 3yr
    I would prefer the use of a PCSK9 inhibitor in this patient since he/she has the mutation of the LDLR and PCSK9, patient with this mutation has PCSK9 which is uninhibited leaving to degradation of the LDLR which then is not available to remove the LDL
  • 3yr
    Max tolerated statin(atorva or resouva) and then add PCSK9i. Check the hs-CRP level to see systemic inflammatory levels.
  • 3yr
    Agree with the above comments - would be inclined to rosuvastatin and not be shy about using psk9i. If patient not receptive , then would add bemp acid .
  • 3yr
    Agree with others; make sure that they're on the right statin (atorva or rosuva) at highest dose, then add PCSK9i, then add ezetimibe, then add bempedoic acid...
  • 3yr
    Agree with others; make sure that they're on the right statin (atorva or rosuva) at highest dose, then add PCSK9i, then add ezetimibe, then add bempedoic acid...
  • 3yr
    review diet and nutrition and current meds, add PSK9 if needed
  • 3yr
    I agree with others, a high dose statin, evaluate LDL after statin initiation add ezetimibe 10mg if LDL not at goal of less than 100mg/dL, low cholesterol diet and exercise are essential and decreasing all other modifiable CVD risk factors such as smoking
  • 3yr
    I add zetia then ask patient if they are comfortable using a PCSK9….if not I use nexlizet
  • 3yr
    Up titrate statins to full dose, add ezetimibe. Add PCKS9. Almost always does the trick
  • 3yr
    I replace weaker and lower dose statin with more potent statin, either rosuvastatin 40 mg daily or atorvastatin 80 mg daily (at bedtime for best effect) if tolerated. I thoroughly educate the patient in the benefit of a whole food plant based diet. For the most motivated patients, the portfolio diet is prescribed. If LDL cholesterol is too far from goal, I recommend PCSK9 inhibitor therapy next, particularly in the younger and middle age patients. If insurance coverage cannot be obtained for PCSK9 therapy, then ezetimide is added to high dose statin. I hope to prescribe inclisiran in the future to those who are statin intolerant. The LDL cholesterol goal is ,70 mg/dl for primary prevention and <55 mg/dl for secondary prevention.
  • 3yr
    I would maximize the statin dose then would add PCSK9 inhibitors or add inclisiran. Continue to stress reduce oral intake of saturated fats
  • 3yr
    I add on a PCSK9 inhibitor to the maximally tolerated statin dose. I've had good results with this combination. I haven't used inclisiran as of yet due to logistical issues
  • 3yr
    In addition to diet and exercise along with maximally tolerated doses of statins, would prescribe PCSK9 inhibitors. Inclisiran can be considered as well instead of PCSK9
  • 3yr
    I focus on nutrition referral for diet control,high dose statin rx as tolerated,add Zetia if not at goal.
    If this does not achieve goal then go to PCSK9 out of pocket cost needs to be considered otherwise patient is going to stop treatment.
  • 3yr
    Would use PCSK 9 inhibitors and refer to specialty clinic
  • 3yr
    Address the dinner table first - most families also eat together. Stress that diet is important too and improve this as possible. Then start with high potency / dose statins and PCSK9-Is also as needed. Must actually recheck the labs to ensure getting improvement with these. Also encourage exercise.
  • 3yr
    Familial hypercholesterolemia requires multimodal treatment with a PCSK9 inhibitor, HMG inhibitor, absorption blockers and whatever else it takes to get the LDL to a safe level because of the risk of early cardiac death if untreated.
  • 3yr
    I use high intensity statin + zetia. Check for compliance is important. I will usually add rapatha, praluent, or leqvio. Leqvio is great as it is dosed twice a year and can be done in the office. I do not have much experience with nexlizet.
  • 3yr
    I would suggest high intensity statin followed by Zetia, and possibly nexletol. Also inclisiran or other PCSK9i are great options, along with a plant-based diet.
  • 3yr
    i have used zetia, repatha, praluent and levqio, nelixet in addition to statins.
    it depends on their comorbid conditions and insurance coverage.
  • 3yr
    addition of statin, fibrates, zetia. multiple approach needed for optimal control
  • 3yr
    PCSK9 inhibitors are the mainstay of treatment. Also Leqvio (siRNA) and Nexlotol (ACL).
  • 3yr
    These patients need aggressive management. I do initially try lifestyle modification. Thereafter use combination therapy with statin and Zelia. I do however have a low threshold for proceeding to PCSK9 inhibitors sometimes in combination with other agents. Good control can be obtained with this strategy.
  • 3yr
    This in when lifestyle changes and education on dietary habits are of utmost importance. Thr PCSK9 inhibitors will also help.
  • 3yr
    Where's the money?
  • 3yr
    I recommend starting a PCSK9I (Repatha or Praluent) and possibly Leqvio. For patients who are just mildly above goal LDL or who refuse an injection, I would start Nexlezet in addition to maximally tolerated statins.
  • 3yr
    Virtually all of these patients require a PCSK9 inhibitor or Leqvio in addition to fmaximal dose statin (as tolerated) or adequate LDL reductions
  • 3yr
    I advise a good multiple, fish oils and I look at blood type
    Exercise
    Hydrate
    Etc
  • 3yr
    High potency statin rosuvastatin 20mg plus 10mg ezetimibe plus 30 min excercise daily and low cholesterol diet. Akso PCSK9 inhibitor such as Praluent or Repatha
  • 3yr
    Agree with the other comments, high dose statin is necessary and quite likely a psk9i to have meaningful clinical effect.
  • 3yr
    Would try maximally tolerated statin - at least 20 mg Rosuvastatin + PCSK9 inibitors
  • 3yr
    Would recoomend high potency statin that can achieve quite a substantial decrease in LDL. Combination agents is also an option as importantly to encourage a low cholesterol diet and exercise.
  • 3yr
    High potency statins in everybody, like Rosuvastatin 20mg daily and add ezetimibe 10mg daily with low lipid diet and exercise.

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