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Has anyone here combined ezetimibe and rosuvastatin? Dr Brewer, your opinion please.

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  • Has anyone here combined ezetimibe and rosuvastatin? Dr Brewer, your opinion please.

    I ask this because an RCT showed significant improvement in inflammation markers when both were taken in combination:

    Comparison of the effect of rosuvastatin versus rosuvastatin/ezetimibe on markers of inflammation in patients with acute myocardial infarction

    In particular, the Lp-PLA2 dropped significantly more when with the combination:
    "The addition of ezetimibe to rosuvastatin led to greater reduction of LDL-C compared with rosuvastatin monotherapy (from 3.00 to 1.19 mmol/l vs. 2.93 to 1.49 mmol/l, respectively; P<0.05), as well as reduced levels of hs-CRP (from 5.15 to 0.68 mg/l vs. 4.33 to 1.49 mg/l, respectively; P<0.05) and Lp-PLA2 (from 333.13 to 79.07 mg/l vs. 327.95 to 123.62 mg/l, respectively; P<0.05)."

    I am currently taking rosuvastatin monotherapy but if I can further decrease the Lp-PLA2 with the addition of 10mg of ezetimibe (Zetia) then I'll try to get one of my GPs to prescribe it.

    I would like to take pitavastatin rather than rosuvastatin but the commercial price is very high. Canadian pharmacies sell a much cheaper generic version, but I think it is manufactured in India, and Indian generic drugs have quality control problems. Also, I doubt the ignoramuses at the VA would be willing to prescribe it for me even though it is in the VA formulary. They still think that the purpose of statins is to reduce LDL-C, not inflammation.

  • #2
    The study was limited (or not powered sufficiently as researchers would say) to make a definitive conclusion. The below statement sort of sums it up: "Although the addition of ezetimibe to rosuvastatin resulted in a greater reduction of Lp-PLA2, the difference between the monotherapy and combination treatment did not achieve statistical significance in prespecified subgroups".

    I have heard that some lipidologists favor a low dose statin with ezetimibe as an excellent alternative to a high dose statin. I would take the combination myself.

    If you don't hear back from Dr. Brewer on this topic, mention it in the comments section of one of his videos as I think he monitors those more frequently.


    • fatmax
      fatmax commented
      Editing a comment
      It achieved statistical significance with the entire population of 113 patients.

  • #3
    The JUPITER trial showed about a 33% reduction in Lp-PLA2 in one year for patients taking 20mg rosuvastatin monotherapy and about 12% reduction for those taking the placebo:

    If the results in the Chinese combo trial are credible, they showed a 76% reduction in Lp-PLA2 in one year for those taking the 10/10 dual therapy and a 62% reduction for the 10mg rosuvastatin monotherapy. However, the patient population here had had a recent heart attack and must have had massive inflammation as well, unlike in the JUPITER trial which was composed of 17,802 men and women without cardiovascular disease or diabetes at study entry.

    In 9 months of taking 20mg rosuvastatin, my Lp-PLA2 has decreased by 20%. If no further reduction is shown by September then I'm going to switch to 10/10.


    • #4
      I'm late to the party, but I'm on rosuvastatin-20 + ezetimibe. Drives LDL-P into the floor. So much so that I've been half dosing the ezetimibe. I think how efficacious it is depends on your diet and genetics as well though.


      • fatmax
        fatmax commented
        Editing a comment
        Can you provide some inflammation numbers, please? What are your LDL-P, LDL-small, and LDL-medium numbers? What is your LP-PLA2? How have these values changed over time? Have you had a CAC scan?

    • #5
      Sorry I missed this... Here's my latest CardioIQ panel. This is on rosuvastatin-20mg + ezetimibe-5mg (half dosing):

      LDL-C 22mg/dL
      HDL 51mg/dL
      Trig 41mg/dL
      Total 85mg/dL
      LDL-P 493nmol/L
      LDL-small 101nmol/L
      LDL-medium 75nmol/L
      HDL-large 4113nmol/L
      LDL peak size 210.3Å
      ApoB 37mg/dL
      hsCRP <0.3mg/L
      LP-PLA2 71nmol/min/mL

      As a footnote, this is after 2 weeks of going off the ketogenic diet and onto a low-carb (but not ketogenic) diet. A previous test during moderate ketosis showed very similar results, with the exception of Lp(a), which increased from 76nmol/L (on keto) to 122nmol/L (on low-carb). 2+ years of the ketogenic diet has been quite efficacious for improvement of nearly all health markers; however, I recently found I had hypopituitarism, which seems to have resolved with the increase in carbohydrate. This is an experiment in process, so I'd say conclusions regarding causality are pending. MRI showed no adenoma or other abnormality in the HPA axis, so there does seem to be some dietary effect.


      • #6
        This opens up a whole new dimension to control of atherosclerosis, in my opinion. These are the most interesting numbers posted on this forum since those of John L. Thank you for sharing them. Your dietary and medication regimen seems to have resulted in an extremely high Pattern A/B ratio. You must surely have virtually no glycated or oxidized LDL whatsoever. I think it is reasonable to conclude that you have stopped the progression of inflammation, as indicated by your excellent LP-PLAC2, yet your HDL is only 51 and HDL-large is only 4113. This raises other questions which I hope will help with. Are you taking niacin? How long have you been taking the ezetimibe? What is your fasting BG and insulin? Are you taking metformin? What vitamins and supplements are you taking? How are you exercising? Thanks again and best of luck. Please keep participating in this forum. What you are doing is innovative and valuable.
        Last edited by fatmax; 06-30-2019, 05:30 AM.


        • #7
          Before statin therapy, with no pharmaceutical intervention, my HDL was primarily controlled by exercise load and diet. It was ~40mg/dL without exercise, regardless of diet. With exercise and a ketogenic diet, it was ~90mg/dL. I am not taking niacin, as I remain unconvinced it is efficacious for outcomes. It does raise HDL, but I agree with the cardiologists (rather than this forum) that raising HDL medicinally is of no benefit. I don't believe HDL is 'good'; it is 'benign'. The only relevance it has is that it's subtracted from total cholesterol to isolate the portion of concern. You can't knock down total cholesterol this low and still have high HDL, and chasing HDL is futile anyway.
          I have been taking ezetimibe for a year, although I have modulated it on and off depending on my liver function tests. Contrary to current thinking in Cardiology, I've found that ezetimibe drives up my AST/ALT more than statins; that could be due to my dietary pattern; I don't know, but the effect has been reproducible over several lipid panel tests. A half dose (5mg) has been highly efficacious and keeps my LFT hovering around the upper limit of normal. I'm satisfied with that, and my cardiologist has in effect given me free rein to modulate as I see fit, as long as my non-HDL cholesterol stays under 70mg/dL, which is quite easy.
          Fasting BG on the ketogenic diet was in the 80s [mg/dL], but after stopping ketosis, it's now in the 90s. This is something I'm not very happy about, but if I have to take that hit to normalize my endocrine panel, I will. Insulin has not been measured. I'm not taking metformin or berberine. Postprandial BG response to whole foods carbohydrate challenges of 30~80g seem well controlled. Supplements are: multivitamin, fish oil and/or cod liver oil, 5000IU Vitamin D, 300mg CoQ10, magnesium citrate. Exercise is ~5 days per week moderate cardiovascular, fasted, either 60 minutes on the rower, or 110 minute walk/jog through hills.


          • fatmax
            fatmax commented
            Editing a comment
            Thanks again for the information. Your results seals the deal for me: I'm going to get a prescription for ezetimibe. I've pretty much followed a similar dietary path, supplements, and exercise as you for the past 18 months. I've been taking 20mg rosuvastatin and 1g niacin per day. I've been concerned that niacin is indeed not as beneficial as we might hope, as you mentioned. My Lp-PLA2 is not decreasing as rapidly as I would like. I've got to stop the progression of the inflammation, and I've done about as much as I can with lifestyle and diet. Thanks again for your help. If your cardiologist has shared any other information regarding his experiences with the rosuvastatin/ezetimibe combination, please let the forum know.