I skimmed through the high level review articles on statins. I say skimmed because the Cochrane Systematic Review is 402 pages, which is typical of their in depth reviews. Below is my take aways on each of the papers.
Overall, they did get me to rethink my dose, particularly the Dimmit 2018 review which puts doses in perspective with their ED50 (Effective Dose for 50% of the population taking them). The ED50 for Atorvastain is only 2mg, but I am taking 10mg (5X the ED50) because that is the lowest dose available in the USA. This discussion has excellent timing because my doctor recently gave me an open lab order for lipids every 4 weeks for as long as I feel the need to do the labs to monitor my return to using the drug after a 2 month vacation (and my lipids going out of range again). So, I think for my next lab, I’ll try a dose of 5mg by cutting the tablet in half. Should be an interesting experiment, as my goal is simply to undo the lipid alterations caused by TRT.
Collins, R., Reith, C., Emberson, J., Armitage, J., Baigent, C., Blackwell, L., Blumenthal, R., Danesh, J., Smith, G.D., DeMets, D., et al. (2016). Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet 388, 2532-2561. Interpretation of the evidence for the efficacy and safety of statin therapy - PubMed
They were certainly in the pro-statin camp. They concluded: It is, therefore, of concern that exaggerated claims about side-eff ect rates with statin therapy may be responsible for its under-use among individuals at increased risk of cardiovascular events. For, whereas the rare cases of myopathy and any muscle-related symptoms that are attributed to statin therapy generally resolve rapidly when treatment is stopped, the heart attacks or strokes that may occur if statin therapy is stopped unnecessarily can be devastating.
Dimmitt, S.B., Stampfer, H.G., and Warren, J.B. (2018). The pharmacodynamic and clinical trial evidence for statin dose. Br J Clin Pharmacol 84, 1128-1135. The pharmacodynamic and clinical trial evidence for statin dose - PubMed
An interesting read. This is the review paper that discusses statins in terms of the ED50. not being an expert on this subject, I’m a bit confused with their conclusions. They lead off with a conclusion that Statin doses around estimated effective dose 50 (ED50) can reduce myocardial infarction by over 25% and mortality by around 10%. Then go on to conclude that for 10 mg of atorvastatin, there is no randomized controlled clinical trial evidence that coronary mortality is lowered, or that survival is increased. But that is 5X the established ED50 for the drug. They do discuss in depth the potential adverse effects in the body of the text and conclude that AEs increase in number and severity with increasing dose. They provide additional discussion of liver function in Table 3 and show a very low effect of 10mg on ALT (increase of 0.2%) compared to a significantly higher (p<0.001) effect of 80mg (increase of 1.2%). I have monitored liver enzymes closely and there appears to be no effect for me. OTC ibuprofen and naproxen have a MUCH greater effect.
Adams, S.P., Tsang, M., and Wright, J.M. (2015). Atorvastatin for lowering lipids. Cochrane Database of Systematic Reviews. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD008226.pub3/epdf/full
They reviewed 296 trials of atorvastain which included 38,817 participants. The data shows that there is a linear dose-related effect on blood total cholesterol, LDL-cholesterol, HDL-cholesterol
and triglycerides. But provide no long-term survival data because most of the studies were shot-term ‘efficacy’ studies. They did point out regarding safety that withdrawals due to adverse effects were not statistically significantly different between atorvastatin and placebo
groups in these short-term trials. They also point out the same limitation on safety conclusions that the review does not provide a good estimate of the incidence of harms associated with atorvastatin because included trials were of short duration and adverse effects were not reported in 37% of placebo-controlled trials.