Another failed cholesterol drug study

cstehansen

http://www.jwatch.org/na44100/2017/05/17/another-cetp-inhibitor-yet-another-negative-study?query=etoc_jwcard&jwd=000020101711&jspc=US

This is from the New England Journal of Medicine. The drug successfully lowered LDL significantly and even raised HDL, but the results in terms of death, heart attack, etc. were no better.

This continues a long line of studies where cholesterol levels are shown to either have no correlation or, in some studies, an inverse correlation with these results.

The article allows comments, so I left the following:

It seems I keep seeing studies where cholesterol values do not line up with expected end points. In fact some, especially with older people, seem to have an inverse relationship. Perhaps the only reason the JUPITER trial showed a positive result was because they only tested on those with high inflammation markers (hsCRP above 2 with an average over 4.5 if memory serves me), and that the inflammation markers were significantly improved with the drug.

Maybe we should be looking at inflammation lowering (hsCRP in particular) in addition to or possibly even instead of cholesterol in terms of changing outcomes.

I won't hold my breath that my comment will make it past the moderator.

canadjineh

Also regarding JUPITER, this....

Issues Related to Early Trial Termination
Trials stopped early for benefit can overestimate treatment effects, especially when the expected number of events is low.12, 13 Compounding this issue is the fact that details of the reasons for stopping are often not reported, and effect estimates are rarely adjusted for the number of interim analyses and decreased sample size associated with stopping early.8 Despite these issues, this practice has escalated in recent years.13 The ethical rationale for stopping a trial early is to offer the beneficial intervention to the control arm and to disseminate the new findings as early as possible. However such motivation is often not justified. The rationale would hold if, once the information was made available, patients had a greater than 50% chance (i.e., greater than their randomization probability) of receiving the intervention in clinical practice. However, this seems unlikely given known delays in dissemination and translation of new trial results into practice.14

Stopping trials early for benefit can also be ethically questionable because of reduced information on other outcomes and long-term risks that would otherwise accrue.15 Thus, ethical requirements for the risk-benefit ratio may be violated when trials are terminated early. These considerations would seem to apply to JUPITER which was stopped after only 1.9 years of the planned 4 years. In the case of JUPITER, for example, we will never know the long-term consequences of the higher glycated hemoglobin levels and incidence of diabetes that were observed in the rosuvastatin group, or the long-term effects of lowering LDL cholesterol to levels below 60 mg/dL, which were never attained in previous randomized trials. Cholesterol is a physiological molecule required for many vital processes. Long-term safety is a concern especially because randomized trials carefully screen out subjects who have comorbidities or are otherwise at risk of suffering side effects from the tested drug. This is less likely to occur in regular clinical practice. Of note, subjects with a history of diabetes, uncontrolled hypertension, renal dysfunction, cancer within 5 years and many other comorbidities were excluded from JUPITER.

https://ncbi.nlm.nih.gov/pmc/articles/PMC2798141/

canadjineh

I've been researching some of this stuff because my mom is on statins, AND has muscle pains (although perhaps attributed to other causes), worsening dementia, and low level T2D....
Statins haven't been proved to help for women anyhow.