3 ms·
Again, this paper does not support what you're saying it does at all. You are either misreading or intentionally distorting what it says. 1) Patients had a bas
by et2o 8y ago
Again, this paper does not support what you're saying it does at all. You are either misreading or intentionally distorting what it says.
1) Patients had a baseline cholesterol of 106 mg/dL. So already pretty good control of lipids. This implies they were already on intensive statin therapy, and so the effect of PCSK9is can be only incremental improvements. Given that you say PCSK9is are more specific to cholesterol (although this is debatable), we can thus probably attribute most of the effect to reduction in LDL.
2) I quote:
Treatment with a PCSK9 inhibitor was associated with a lower rate of
a) myocardial infarction (2.3% versus 3.6%; odds ratio [OR]: 0.72 [95% confidence interval (CI), 0.64-0.81]; P<0.001)
b) stroke (1.0% versus 1.4%; OR: 0.80 [95% CI, 0.67-0.96]; P=0.02)
c) coronary revascularization (4.2% versus 5.8%; OR: 0.78 [95% CI, 0.71-0.86]; P<0.001).
d) All cause mortality was only marginally significant: all-cause mortality (OR: 0.71 [95% CI, 0.47-1.09]; P=0.12).
This does not mean PCSK9is don't reduce mortality, it just means that we haven't followed enough people for long enough. Again, you have to understand how null hypothesis testing works to interpret this statement. The reason that they reduces MI and Stroke without the same effect on reducing all-cause mortality is that we treat MI and Stroke pretty well typically, so you usually don't die from them. The event rate for these is higher, which means if you run a trial for them as the outcome instead of all-cause mortality you can use fewer patients and get it done faster and cheaper, which is ultimately good for patients. However, we obviously know that MI and Stroke are associated with increased risk death. Furthermore, you can die from a lot of other reasons than cardiovascular disease, which makes the trial require even more people to separate out the signal.
No one is arguing that PCSK9 inhibitors are a magic bullet (well maybe someone is, but not most people), but they are clearly pretty good even when added to already-pretty-good therapy.
- AstralStorm 8y agoThis is an interesting definition of marginal significance, with P=0.12 (more than double the standard 0.05) and 10%+ OR overlap. You seem to be focusing on OR means too much. Absolute risk adjustments are surprisingly low considering certain predictions. I agree with the conclusion that 106 mg/dL mean could've reduced the power of the experiment. I also agree that a good followup is relevant and important. It could change results a lot, including the initial positive results. However, in the meantime, we have no way to actually evaluate the risks and are essentially making educated guesses. Note that the patients treated were on average 60 years old. This reduces followup time considerably but also reduces potential effect size. The results are mostly based on ODYSSEY LONG TERM and FOURIER trials. The former verified PCSK9i alongside high dose statin therapy. The latter used a monotherapy in some cases but not defined the subgroup. FOURIER alone is quite damning. ODYSSEY LONG TERM does not consider mortality endpoints. Such interesting tidbits like "In terms of individual outcomes, evolocumab had no observed effect on cardiovascular mortality, and hence P values for other outcomes should be considered exploratory." The inhibitors in question were allegedly not mainly tested here as an adjunct to statin therapy or replacement for resistant cases, but it so happened anyway. You're supposed to be comparing it to current best known treatment which is statins, which is a very valid comparison. Any other comparison would only be of educational value but should be done regardless. It is even more suspect that it was not done but instead it was used as an adjunct. Not even canadian cross design was used...
- et2o 8y agoIt seems like your argument strategy is to throw out 10 different ideas. I refute them, then you throw out 10 more. Meanwhile you ignore any evidence I provide. This is not an honest conversation and no evidence is going to change your mind. I feel like a global warming scientist.