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July 17, 2021

A 66 year old female college professor is seen in your office after undergoing an ‘executive physical’ which included an EKG, GXT, and coronary calcium score. She is asymptomatic, exercises regularly, and is a lifelong non-smoker. She has well-controlled hypertension and takes Losartan/HCTZ 100/25mg daily. Her coronary calcium score is 843 with diffuse distribution of calcification. GXT was normal at a high achieved workload. Weight is 73 kg. BP 130/74. Fasting glucose is 99.



She has been told she has high cholesterol dating back to her 50s. Currently on therapy her total cholesterol is 254, HDL 51, LDL 171, triglycerides 160. Both of her parents had "borderline” cholesterol. She has no siblings. She eats a mostly plant-based diet with occasional ‘indulgences’. Ethanol use is modest: 2-3 glasses of red wine per week. She typically spends 2 months every year on remote field research trips with her students.



She has been on bile acid sequestrants, niacin, ezetimibe, and several statins. She is currently on only simvastatin 40mg every other day. She has had significant myalgias with daily dosing of numerous statins and good relief with drug holidays. Her current regimen is tolerable and she has minimal myalgias. She experiences cramps and diarrhea with ezetimibe.



She is naturally concerned about the elevated coronary calcium score and wishes to know how she can get her lipids to goal. She is willing to make more improvements to her diet and to step up her exercise regimen.

Does her elevated coronary calcium score change your goals for treating this patient’s lipids?

Besides lipid-lowering therapies, what other interventions are appropriate?

What is the next step in bringing her closer to her target LDL level?

  • July 17, 2021
    Can consider to start Repatha along with Aspirin
  • June 12, 2021
    I would consider injectable PCSK9 inhibitor as her LDL goal is < 70, plus ASA 81mg daily
  • May 21, 2021
    As she now has confirmed atherosclerosis, she needs to initiate statin therapy and daily ASA 81mg. I recommend starting rosuvastatin, which has the best data for reduction of CV event risk. this may be tolerated at 10mg daily even with her history of intolerance to other more traditional statins. If not tolerated at all, would start PSK9 inhibitor (e.g., injectable Rapatha) Also, continuing lifestyle efforts should be emphasized. I also recommend pursuing Lexican stress testing to determine clinical effect of the atherosclerosis. appreciate the comments above that statin may increase her CAC, but would not expect it to be that high attributable to statin alone. Her fasting glucose is very near prediabetes and she should be followed closely with those labs as well.
  • May 20, 2021
    There probably isn't a lot of improvement she can do with diet, although a plant based diet can still be carb and fat heavy. I have found rosuvastatin to be one of the best tolerated and effective statins. I would start her on low dose and monitor for SE. CoQ10 might also be helpful. If she isn't able to tolerate, then i would recommend PCSK9 therapy. Her glucose and triglycerides are concerning. This also needs to be explored. With the high calcium score, i would also recommend 81 mg ASA daily if no contraindications.
  • May 19, 2021
    I would work on diet and exercise and lower statin to see if better tolerated and add pcks9 inhibitors with zetia 10 mg po qd as this is often required as step therapy
  • May 17, 2021
    would try other statins at lower doses or QOD, then if not tolerated, I'd add zetia or PCSK9i, fasting BG of 99 is concerning for possible diabetes and at least prediabetes, needs A1C check
  • May 17, 2021
    In glancing at the 2018 flow chart from AHA ACC, there is no recommendation to add a PCSK9 agent for this patient. If her LDL was greater than 190 that class of med can be considered. For this patient the issue is not addressed.
  • May 17, 2021
    I am interested in the comments saying that simvastatin is 'inappropriate' and 'meaningless'. Clearly she is not at (or anywhere near) her target LDL on the current dose but if other statins are even less tolerable, surely it is better than nothing?
  • May 17, 2021
    This a case on primary prevention, as the patient has no history of a cardiac event. A coronary calcium score of 843 is extraordinary high, if accurate. For that alone she should be on a high intensity statin. SImvastatin is an obsolete statin with the potential for many drug interactions so I would use crestor and see if she tolerates it. Always inquire about the specific muscle symptoms to make sure they are consistent and can be traced to a statin. Zetia would be a good add on agent, but apparently she can not tolerate it. For those with a prior MI, a PCSK9 inhibitor would be added such as evolocumab or alirocomab, but the data is less clear for primary prevention as surrogate endpoints were used for addressing outcomes in this population. Icosapent could also be used to get her triglycerides less than 150 but since she is so close to that number it might be achieved with diet and exercise. The benefits of bempedoic acid for primary prevention is not clear. ACC would recommend a statin and PCSK9 for this patient, but American Family Physicians would not. Shared decision making is the key to address these issues.
  • May 17, 2021
    Her LDL goal is < 70
    She was not tolerating statins and zetia well, based on the tests results , her ldl goal should be < 70, will consider Livalo, start Repatha or nexletol, low dose aspirin,
  • May 17, 2021
    Her high LDL and ca score with history of myalgia with statin
    Will add non statin new pKS 9 inhibitors
    Will check TSH
  • May 16, 2021
    I would add a PKS-9 inhibitor and perhaps Nexletol.
  • May 16, 2021
    I definitely would stop simvastatin. It’s not doing anything meaningful, just another pill to swallow. Her target LDL < 70, I would add repatha or praluent, and check TSH. Also add baby aspirin daily.
  • May 16, 2021
    I would switch her to injectable PCSK9 inhibitor
    Her LDL goal is < 70
    She was not able to tolerate several statins in the past and current dose of not a high intensity statin every other day is suboptimal
    This patient also should be on aspirin 81 mg po daily ( calcium score > 100
    She need ischemic evaluation with nuclear medicine stress test
  • May 16, 2021
    Has she tried adding CoEnzyme Q10 to statin to minimize myalgia? Again, with normal CK levels myalgia is not of particular concern. If all else fails, changing to Repatha is indicated. Simvastatin every other day isn't doing much for her. Psyllium fiber (5 capsules twice a day) is known to lower cholesterol, as does the herb Bergamottin.
  • May 16, 2021
    For some one on the statin there is no need to do a Calcium Score as the Utillity of Calcium score is a tie breaker to start some one on statin or not along with the as risk stratification in primary prevention of the CVD Doing a calcium score on some one on the statin does not add more info actaully calcium score gets higher on the statin as the caclum becomes more organized the Blood vessles on statin , If at all if an asymtomatic person like in the vignette needs some thing for the eval of the CAD needs to have the CT Angio of the chest to see plaque burden and then relvant work up if needed , In any event what we have here is challenge of Primary Prevention with the LDL of 171 with some intolerance to statin and total intolerance to Ezetemibe and the LDL needs to be brought down to less than 100 in this scenario and may be less than 70 ideally speaking , Only two options are left in addition to continue with Simvastatin 40 mgm alternate day ( seems that is all she can tolerate for a statin ) and add Nexletol or a PCSK-9 inhbitor , Nextelol is easy to add from the economic and approval point of view adding the PCSK-9 will be challenging from the insurance point of veiw as do not have any any evidence of arterial occlusive diease or diabetes to get it approved ( high calcium score would not make her eligible ) So would go for Nextelol for now and diet modification and see how she does , She may have Familial Hypercholesteremia and that is one indication along with the intolerance to Statin make her eligible for PCSK-9 inhibitor and will be worh while to repeat the lipid profile off the smivastatin after few weeks and see where the LDL number goes and establish that , would add aspirin 81 mgm as well
  • May 16, 2021
    Based on her history, LDL levels, and her high calcium scores, I would use a non statin such as bempedoic acid in order to get her LDL levels under control.
  • May 16, 2021
    Simvastatin every other day is not appropriate. This is a short acting statin. Only atorvastatin (5 mg TIW) or rosuvastatin (2.5 mg TIW) are realistic to dose less than daily. She should be switched to one of these statin regimens if possible. Her losartan/HCT has no proven cardioprotective benefit. Ideally change losartan to telmisartan and HCTZ to chlorthalidone (which could also be dosed TIW). Then, adding a PCSK9 Inhibitor would be appropriate. In addition, low dose aspirin would be reasonable since she clearly has CAD, but no event so far. Also would check an A1c or 2 hour post prandial glucose to be sure that hyperglycemia is not a factor that needs to be addressed.
  • May 16, 2021
    Her CAC puts her in the severe grade, therefore reclassifying her risk up. Her current lifestyle likely would not benefit from much modifications. Because of the statin intolerance, I would check CK levels to ensure the myalgias are not consistent with rhabdo. I would not change to a less myalgia-inducing statins (i.e. rosuvastatin, fluvastatin, pravastatin) as she already reports tolerability to this. Would also consider bempedoic acid for the additional LDL support.
  • May 16, 2021
    Her CAC puts her in the severe grade, therefore reclassifying her risk up. Her current lifestyle likely would not benefit from much modifications. Because of the statin intolerance, I would check CK levels to ensure the myalgias are not consistent with rhabdo. I would not change to a less myalgia-inducing statins (i.e. rosuvastatin, fluvastatin, pravastatin) as she already reports tolerability to this. Would also consider bempedoic acid for the additional LDL support.
  • May 16, 2021
    Assuming all statins have caused side effects would go to Nexletol or Repatha to bring LDL under 55 or at least 70.
    Though ASA for primary prevention in women is shown not to be of benefit- I would recommend baby ASA daily.
  • May 16, 2021
    I would change sim a statin to Crestor and begin at 10mg and try to increase to 20mg. Would consider adding Nexletol if LDL not to goal. I would try to get LDL to less than 70 and based on new guidelines would try for 55 or less. Patient should take ASA 81mg 1 QDay.
  • May 16, 2021
    In light of her history and side effects from statins I am sure that you are leading us to use a nonstatin such as Nexletol.

  • May 16, 2021
    Repatha
  • May 16, 2021
    Family history, Ca score, lipid levels are all signs for alarm. Appears statin history precludes their use. Believe it or not would use Repatha. Sounds drastic but with patient agreement worthwhile. Also would swithc antihypertensive med to Ramipril (HOPE study) with the diuretic.