STUDY: Lowering LDL Not Supported By Evidence

It should come as no surprise that the recently published conclusion by researchers that there is "no high-quality clinical evidence to support currently proposed treatment goals for LDL cholesterol," is being quietly ignored by most of the popular media outlets.

The review, Narrative Review: Lack of Evidence for Recommended Low-Density Lipoprotein Treatment Targets: A Solvable Problem, was published in the October 3 issue of the Annals of Internal Medicine.

While Forbes did carry an article yesterday about the study - Study Questions Value of Lower Cholesterol Targets, it was simply a reprint of the HealthDay News article; which was a repackaging of the press release from October 2, issued by University of Michigan Health System. In fact, as of today, only 16 articles are available online about this study, and that includes the press release!

And of course, you do have to love this headline from HeartWire - No evidence yet for ultralow LDL-cholesterol levels, according to Michigan researchers. [emphasis mine]

Why ignore this study?

Could it be that "[a]fter performing an exhaustive review of existing research on LDL cholesterol and heart health, they [the researchers] conclude that there is no scientifically valid evidence to support the ultra-low LDL target of 70 milligrams/deciliter for very high-risk patients that has been advocated by some members of the federal government’s National Cholesterol Education Program. Further, they suggest that the evidence previously cited to support an LDL goal of less than 100mg/dL for high risk patients also has major flaws;" every marketing and advertising campaign for statins would need a major over-haul?

Just a quick review of the Lipitor webpage detailing how Lipitor lowers LDL cholesterol gives us a clue why Pfizer and others are not jumping up and down with this finding.

If they remain quiet, the public may not hear about how the researchers found "For those with LDL cholesterol levels less than 3.36 mmol/L (less than 130 mg/dL), the authors found no clinical trial subgroup analyses or valid cohort or case–control analyses suggesting that the degree to which LDL cholesterol responds to a statin independently predicts the degree of cardiovascular risk reduction."

This review shatters the diet-heart hypothesis by exposing the theory as unsupported by the evidence.

Now, you may wonder if these researchers are "those quacks" who simply refuse to accept the conventional wisdom that has repeated for decades lowering LDL is important to reduce risks.

Think again.

Back in April 2004, two of the three scientists who conducted this review specifically recommended and supported the use of statins to lower LDL cholesterol to reduce risk. In their previous work, also published in the Annals of Internal Medicine, Pharmacologic Lipid-Lowering Therapy in Type 2 Diabetes Mellitus: Background Paper for the American College of Physicians, they concluded, "Most patients, including those whose baseline low-density lipoprotein cholesterol levels are below 2.97 mmol/L (less than115/mg/dL) and possibly below 2.59 mmol/L (less than 100 mg/dL), benefit from statins. Moderate doses of these drugs suffice in most patients with diabetes."

So these were not nay-sayers about statin therapy. Nor are they now. In fact, in the newly published paper, they specifically go to great lengths to continue recommending statins - not to lower LDL, but because of the "known lipid-independent effects of statins."

In their review of the evidence to find support for the use of statins as a therapy to reduce LDL, and thus reduce the presumed risk from elevated LDL, they found major flaws in the data published, including:

• Not Considering Alternative Hypotheses When Interpreting Experiments
• Mistaking Cohort Analyses for True Experimental Results
• Cohort Analyses Using Clinical Trial Data Must Control for Exposure to the Treatment
• The "Healthy Volunteer" Effect Can Severely Bias Studies Evaluating Treatment Targets
• Ecological Comparisons Are a Very Weak Source of Evidence and
• Framing Treatment Goals as False Dichotomies

This review is one that I consider a "must read" for a number of reasons, including it lays out, piece by piece, how a review should be conducted and what to look for nicely; it was well done and included both experimental and clinical trials; and it exposes the problem assumptions, bias and interpretation can cause, especially over years when no challenge to the hypothesis is accepted.

Real science demands we challenge our beliefs and assumptions - for decades now we've watched as targets were repeatedly lowered the target for cholesterol without any clear, convincing data - while we've been repeatedly told there is data to support each and every decision to lower the targets! All the while, there have been scientists, researchers and medical professionals asking "where's the data?" as they're disparaged, dismissed and mocked for challenging the powers that be.

As is clear in this review, lowering LDL cholesterol below 130 or below 100 or below the new target of 70, has no support in the data, is not based on evidence and is a target without foundation for the marketing or promotion of statins.

But, you're not going to hear about it in the news tonight, nor will your doctor.

Heck, you may want to print a copy of the paper to give to your doctor next time he suggests you start taking a stating to lower your LDL cholesterol to reduce your risks!