#29

I used consensus[.]app AI to ask your question. Here is consensus AI’s answer:

Statin monotherapy vs combination with ezetimibe impact on all-cause mortality

Pro Analysis

Beta · 10 papers

Introduction

The impact of statin monotherapy versus combination therapy with ezetimibe on all-cause mortality has been a subject of extensive research. Statins are widely used to lower cholesterol levels and reduce cardiovascular events, while ezetimibe is often added to enhance lipid-lowering effects. This synthesis aims to compare the efficacy of these two treatment strategies in reducing all-cause mortality.

Key Insights

  • Combination Therapy Reduces All-Cause Mortality in CKD Patients:
    • Statin and ezetimibe combination therapy significantly reduced all-cause mortality and major adverse cardiovascular events compared to statin monotherapy in patients with chronic kidney disease (CKD)2.
  • No Significant Mortality Benefit in Acute Myocardial Infarction (AMI) Survivors:
    • In patients who survived an acute myocardial infarction, the addition of ezetimibe to statin therapy did not show a significant reduction in all-cause mortality compared to high-potency statin monotherapy6.
  • Mixed Results in Diabetes and High-Risk Cardiovascular Disease:
    • Moderate-intensity statin with ezetimibe did not significantly reduce all-cause mortality compared to high-intensity statin monotherapy in patients with type 2 diabetes and very high-risk atherosclerotic cardiovascular disease (ASCVD)1 7 8.
    • However, in patients with acute coronary syndromes (ACS), upfront combination therapy of statin and ezetimibe was associated with a significant reduction in all-cause mortality compared to statin monotherapy4.
  • General Cardiovascular Benefits but No Clear Mortality Advantage:
    • Ezetimibe-statin combination therapy was more effective in lowering LDL cholesterol and reducing cardiovascular events but did not significantly reduce overall mortality compared to statin monotherapy in hyperlipidemic patients with atherosclerosis and/or diabetes mellitus3 5.

Conclusion

The combination of statin and ezetimibe therapy shows varied results in reducing all-cause mortality depending on the patient population. While it significantly reduces mortality in CKD patients, it does not show a clear mortality benefit in AMI survivors or patients with diabetes and high-risk ASCVD. However, it does offer cardiovascular benefits and improved lipid profiles, suggesting its potential utility in specific high-risk groups.

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#30

Thanks, this is a new insight for me and I’m an APOE4 carrier. I was seeing diminishing returns from the higher statin levels my Dr put me on. Convinced them to lower the statin and add ezetimibe, leading to much lower LDL levels. Will go investigate desmosterol.

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#31

That is cool. I need to learn how to use these new tools. Thank you for doing this and sharing the results. Much appreciated!

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#32

One more: Efficacy and diabetes risk of moderate-intensity statin plus ezetimibe versus high-intensity statin after percutaneous coronary intervention 2024

image

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#33

Moderate-Intensity Statin Plus Ezetimibe: Time to Rethink it as an Optimal Initial Lipid-Lowering Strategy 2024

Unlike the European guidelines, the Chinese guidelines recommend upfront use of moderate-intensity statins to achieve the LDL-C target.
Furthermore, the 2023 Chinese guidelines for lipid management recommend combining a moderate-intensity statin with a cholesterol absorption inhibitor as a core strategy to achieve LDL-C goals when a moderate-intensity statin does not yield the desired effect. These recommendations represent a shift from the conventional high-intensity statin–based treatment approach.

We’ll see if Europeans and Americans follow in their updates guidelines in the next few years…

Efficacy and safety of moderate-intensity rosuvastatin plus ezetimibe versus high-intensity rosuvastatin monotherapy in the treatment of composite cardiovascular events with hypercholesterolemia: A meta-analysis 2024

The meta-analysis described 21 RCTs involving 24592 participants. The findings indicated that moderate-intensity statin combination therapy improved low-density lipoprotein cholesterol (LDL-C) (MD -8.06, 95% CI [-9.48, -6.64] p < 0.05), total cholesterol (TG) (MD -5.66, 95% CI [-8.51, -2.82] p < 0.05), and non-high-density lipoprotein cholesterol (non-HDL-C) (MD -17.04, 95% CI [-29.55, -4.54] p < 0.05) to a greater extent and superior in achieving LDL-C <70 (RR1.26, 95% CI [1.22, 1.29] p < 0.05) and LDL-C <55 (RR1.66, 95% CI [1.56, 1.77] p < 0.05) ratios and in the incidence of adverse events than the high-intensity Rosuvastatin monotherapy group. However, there was no statistical difference between the two in improving HDL-C, total cholesterol (TC), and preventing long-term composite adverse cardiovascular events (ACE).
Moderate-intensity statin plus ezetimibe with combination therapy had better efficacy and safety than high-intensity statins. Future validation is needed with more long-term high-quality large samples.

Ezetimibe plus statin combination vs. double dose statin for patients with dyslipidemia and ASCVD risk: A Systematic Review and Meta-Analysis 2024

Ezetimibe plus statin was associated with a decrease in low-density lipoprotein (LDL) levels [MD: -13.69 with 95% CI (-15.64, -11.74), P <0.01], and more patients achieving their targeted LDL levels [OR: 2.89 with 95% CI (2.40, 3.47), P <0.01]. However, there was no significant difference between the two groups regarding any adverse events [OR: 0.98 with 95% CI (0.89, 1.08), P =0.62], and the composite endpoint of cardiovascular death, major coronary events, or nonfatal stroke [OR: 0.72 with 95% CI (0.39, 1.32), P = 0.29], although there was a trend towards better results for patients with the combination regimen.

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#34

If there is no difference in ACE between the two, then according to the first study, the combo had a better safety profile. In the second, neither outcomes nor safety were different, but the combo achieved better ldl lowering. Not as ringing an endorsement as one would wish. I guess non-significant trend lines are also better for the combo.

I’m curious about comparing HIS+EZE vs MIS+EZE.

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#35

New papers, as usual, the ezetimibe combo is non-inferior.

The clinical effectiveness and safety of low/moderate-intensity statins & ezetimibe combination therapy vs. high-intensity statin monotherapy: a systematic review and meta-analysis 2024

15 studies encompassing 251,450 participants were included in our meta-analysis. In our pooled analysis of observational studies, combination therapy was associated with lower rates of the primary composite outcome (HR = 0.76, CI 95% [0.73, 0.80]), cardiovascular death (HR = 0.80, CI 95% [0.74, 0.88]), all-cause death (HR = 0.84, CI 95% [0.78, 0.91]), and non-fatal stroke (HR = 0.81, CI 95% [0.75, 0.87]). However, the pooled analysis of RCTs did not demonstrate a statistically significant difference between both arms concerning clinical endpoints. Combination therapy had a higher number of patients with LDL-C < 70 mg/dL (RR = 1.27, CI 95% [1.21, 1.34]), significantly lowered LDL-C (MD = -7.95, CI 95% [-10.02, -5.89]) and TC (MD = -26.77, CI 95% [-27.64, -25.89]) in the pooled analysis of RCTs. In terms of safety, the combination therapy lowered muscle-related adverse events (RR = 0.52, CI 95% [0.32, 0.85]) and number of patients with liver enzyme elevation (RR = 0.51, CI 95% [0.29, 0.89]) in the pooled analysis of RCTs and was associated with lower rates of new-onset diabetes (HR = 0.80, CI 95% [0.74, 0.87]) in the pooled analysis of observational studies.

Alternative LDL Cholesterol–Lowering Strategy vs High-Intensity Statins in Atherosclerotic Cardiovascular Disease: A Systematic Review and Individual Patient Data Meta-Analysis 2024

Individual patient data from 2 trials including 8180 patients with ASCVD (mean [SD] age, 64.5 [9.8] years; 2182 [26.7%] female; 5998 male [73.3%]) were analyzed. The rate of the primary end point did not differ between the alternative strategy and high-intensity statin strategy groups (7.5% [304 of 4094] vs 7.7% [310 of 4086]; hazard ratio, 0.98; 95% CI, 0.84-1.15; P = .82). The mean (SD) LDL cholesterol level during treatment was 64.8 (19.0) mg/dL in the alternative strategy group and 68.5 (20.7) mg/dL in the high-intensity statin strategy group (P < .001). The alternative strategy group had a lower rate of new-onset diabetes (10.2% [271 of 2658] vs 11.9% [316 of 2656]; P = .047), initiation of antidiabetic medication for new-onset diabetes (6.5% [173 of 2658] vs 8.2% [217 of 2656]; P = .02), and intolerance-related discontinuation or dose reduction of assigned therapy (4.0% [163 of 4094] vs 6.7% [273 of 4086]; P < .001).

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#36

Wow, ezetimibe is no joke. For the past four months I took 10mg/day, and then the past few weeks or so I switched to 10mg ezetimibe+10mg atorvastatin combo therapy. Additionally, there were a few weeks where I ran out of ezetimibe and took 5-10mg/day rosuvastatin monotherapy.

Full disclosure, I’ve also been taking anabolic steroids over that time period, which are known to elevate blood lipids. My total testosterone and free testosterone just came back as 2,465 (ref range 264-916) and 190 (ref range 5-21), respectively.

Despite this, my LDL-C and ApoB just came back at 46 and 42, respectively. Triglycerides also look great at 37. Prior to starting my lipids were already pretty good (ApoB of 71), but it’s impressive that they’ve improved relative to that despite the drastic increase in testosterone levels.

A few other results are more concerning, and I’m considering ending the cycle at 16 weeks rather than 20, but it’s at least good to see that my blood lipids have remained in check.

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#37

Do you mind sharing the more concerning results? Do they have to do with elevated liver and/ or kidney values?

1 Like
#38

  • Probably my biggest concern is the increase in RBC, hemoglobin, and hematocrit. My hematocrit is now out of range at 52.3%, whereas before it was only 43.9% (19.1% increase). My RBC only increased from 5.67 to 4.9 (15.7% increase), so probably with increased water intake I can get my hematocrit a little lower.

  • I’m getting conflicting answers on whether secondary erythrocytosis from testosterone is actually dangerous, so that’s something I’d like to ask the experts here. I haven’t noticed any obvious symptoms throughout the cycle, other than increased redness for awhile (which went away) and some shortness of breath (which also mostly went away). I have had a sense of chest heaviness the past couple days ever since I read these results, which perhaps is just psychosomatic.

  • Aspartate aminotransferase (AST) increased from 47 to 32 and is now out of range, and eGFR decreased from 119 to 99. Other liver and kidney markers have remained within range. Urine pH was elevated at 8.0 (previous test was 7.0).

  • Prolactin has shot up from 10.9 to 50.6, which is quite elevated. My libido has remained quite stable and I suspect this is why. I’ve also been taking the MOR agonist 7-HO-mitragynine daily for the past few months which could be contributing. Have some cabergoline on the way (which is no joke of a drug) because I would like to briefly see how I feel with low prolactin levels.

  • Estradiol has increased from 28.9 to 86.5, which is quite elevated. Not so worried about this as I haven’t had any bothersome symptoms, although probably it’s contributing to the elevated prolactin.

  • My DHEA-S has always ran high, and it’s taken a hit, going from 533 to 338.

  • Glucose control appears stable considering HbA1c hasn’t changed, but insulin sensitivity has dipped a bit (fasting insulin from 4.7 to 7.3

  • I was surprised to see Vitamin D (25-Hydroxy) take a hit, going from 50.8 to 32.2, which is the very low end of the range.

  • T3 (free) is elevated now also, as it’s gone from 4.5 to 4.2. My thyroid signaling knowledge is elementary, so I would appreciate input on that one.

  • Lastly, systemic inflammation has perhaps gone down, as CRP went from 1.16 to 0.55. I also tested TNF-A as a novel inflammation biomarker, and it’s at 0.8 pg/mL (range 0.0-2.2). Neutrophil-to-lymphocyte ratio did increase from 1.27 to 1.7, which seems unfavorable.

Would really appreciate input on any of these. If you think I’m an idiot for continuing this cycle, please tell me. Likewise if there’s some obvious intervention that might help any of these biomarkers. Although I’ve definitely improved my physique, I haven’t made as many gains as I would like, which is why I want to run it a little longer. Mostly it comes down to not eating enough I think, which is the hardest part for me. But I’m already shut down so figure it’s better to try and really lock in for a few more weeks for some incremental gains.

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#39

Worded kind of funny, like you mixed up the from and to. You mean it used to be 32, which was in range, and now it’s 47? You could try TUDCA for this. It works like magic on these numbers and I’ve taken it for a while and there really aren’t any side effects that I’ve noticed.

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#40

I mixed those up, my bad. I’ll look into TUDCA, thanks for the recommendation!

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#41

Check this thread for TUDCA: UDCA (ursodiol) / TUDCA for healthspan and lifespan?

I don’t take it but for high AST and other liver markers it seems to work well and to be safe.

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#42

No, not an idiot, but I don’t think you’ll get good cycle advice here and this forum isn’t friendly towards PED use, so advice will be skewed and tends to be over cautious and uninformed on this subject. I’d suggest joining Chase Iron’s discord or at least hanging out on meso-rx, professional muscle, t-nation, steroid source talk, enhance genetics etc.

That said, 52.3% with that RBC sounds like a hydration issue (what is the hemoglobin level?), and most manage it also with daily cardio that includes at least some HIIT. That’s considered mandatory if you’re going to use gear. But nobody doing cycles is worried about 52.3%. There’s a lot of discussion on this topic on excel male dot com and by YouTube doctors. None are worried about erythrocytosis causing clotting, but some worry about arterial shear stress over time. But 52.3 isn’t enough to worry about regardless.

Your liver enzymes aren’t bad for what you’re doing. Add NAC. Take som astragalus for your kidneys, but your eGFR probably dropped because of muscle turnover and mass. Get a cystatin C and use the national kidney foundation calculator.

Estradiol is fine for your T levels, but does put you in gynecomastia territory. Same comment on the prolactin. I’d knock the estradiol down below 60, maybe to 40.

It seems like your biggest issue is that you’re wasting time doing this and stressing yourself body for no good reason if you’re not eating enough. You can’t be afraid to gain some fat. I’d discontinue if you can’t maintain a surplus and train very hard because otherwise you’re just spinning your wheels.

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#43

Thank you, this is all very helpful information. @AgentSmith

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#44

@jnorm ezetimibe will bump your liver enzymes. An AST of 42 isn’t too bad but if you are concerned you can take 1/2 or even a 1/3 of that 10 mg dose and get pretty much the same effect on your lipids. That will likely allow your AST to return to normal. I’d do that before I added TUDCA.

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#45

What dosage are you taking to get total T of ~2400, if you don’t mind me asking?

#46

400/week of the cypionate ester. IM’ing EoD.
That was my trough iirc.

#47

I’ve always wondered how it scales. Does T go up linearly with dose, or is there a curve? Probably individual.

#48

One more piece of evidence: Cardiovascular Health - #1725 by RapAdmin

Pooled analysis revealed that combination LLT significantly more effectively reduced the LDL-C level from baseline (mean difference, −12.96 mg/dL; 95% CI, −17.27 to −8.65; P<.001) and significantly reduced all-cause mortality (OR, 0.81; 95% CI, 0.67 to 0.97; P=.02), major adverse cardiovascular events (OR, 0.82; 95% CI, 0.69 to 0.97; P=.02), and stroke incidence (OR, 0.83; 95% CI, 0.75 to 0.91; P<.001), with an insignificant effect on cardiovascular mortality (OR, 0.86; 95% CI, 0.65 to 1.12; P=.26) when compared with statin monotherapy. The risk of adverse events and the therapy discontinuation rate were comparable between groups.

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