IMPROVE-IT study: Desperation of the Statin Industry

IMPROVE-IT touts ezetimibe and simvastatin therapy results as guidance to load up patients with ever higher doses of statins, satisfying the mythical NNTI of 100 patients dosed per 2 magical, precise, exact reductions of CVD incidence over 6 years.  Common sense would indicate that if you did nothing, normal variation would generate the same results given that there will never be 100% incidence of anything.  The impact of various statins piled one on top of each other in cardiovascular medicine is already being exaggerated based on a literal 1% decrease in incidence which could also easily be had by statistical manipulation. 

Stopping short of cutting cholesterol synthesis altogether, the ever lower recommendations for LDL to definitive hypocholesterolemia levels, which generates its own set of diseases such as increased infection and hemorrhagic type cerebral stroke, the ludicrous idea offered seriously to lower LDL levels in the populace to 60mg/dL and below will cause a whole swath of new death by low cholesterol.  What it says to the astute observer is that the normal range of LDL has never been culprit to atherosclerosis leading to ischemic events and that other unrecognized factors are causal, such as oxidation of cholesterol and proteins.

We're not seeing a remarkable 50% reduction here, just a flutter.  Moreover, the rate of death is exactly the same, barring a 0.1% difference.  For other drugs in oncology, this would be considered an unmet endpoint, and the drug would be canned, but not for the statin industry, whose sales must always increase year over year in order to inflate their stock price like other unrelated products.

IMPROVE-IT results

The real world data is that serum cholesterol levels are not related to CVD disease....at all.  Other factors associated with its transport do, but not cholesterol levels.  It is misdirected effort to reduce LDL-cholesterol across the board to hypocholesterolemia levels, especially as it pertains to the importance of cholesterol synthesis to cognition.  The thing with statins is that they are not targeted to particles, proteins, glycoproteins, etc.  They are designed to poison the mevalonate pathway, indiscriminately lowering cholesterol synthesis everywhere, having nothing to do with ApoB, ApoA, ApoE, ApoC, ApoJ, apo(a), triglycerides, phospholipids, plasmalogens, particle number, particle size, etc.  They have been proven dozens of times to have zero effect on the particle that is extremely more atherogenic than LDL, Lp(a), which nobody seems to check for.  One day in the future, it will be considered medical negligence not to check for Lp(a).  Statins do sometimes offer an anti-inflammatory mechanism, which may actually be their mode of action rather than poisoning the cholesterol synthesis enzyme chain.  The fact that lowering cholesterol lower and lower and lower had no benefit against heart disease says something to the tune of "obvious."

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Real world data: Zero correlation (0.0) between cholesterol and heart disease.