Researchers question evidence for ‘the lower the cholesterol, the better’ mantra

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The Cholesterol Treatment Trialists (CTT) Collaboration is UK-based collection of doctors and researchers who, on the whole, push for aggressive treatment of cholesterol to low levels. I don’t think it would misrepresent the CTT’s view that, as far as supposedly unhealthy ‘LDL-cholesterol’ levels are concerned, ‘the lower the better’ for individuals deemed to be at heightened risk of cardiovascular diseases such as heart disease and stroke.

Some doctors and researchers have been critical of the CTT’s stance, however. Recently, for instance, a group from the Mike Rosenbloom Laboratory for Cardiovascular Research, at McGill University Health Centre in Quebec, Canada, published an article in the Journal of Clinical Lipidology which raised a number of issues regarding the evidence for the CTT’s stance [1].

The Canadian group focused on 5 studies [2-6] which the CTT used to support its recommendations for intensive statin therapy. These 5 studies were cited by the CTT as part of a larger review published in the Lancet medical journal earlier this year [7] and previously in 2010 [8]. According to the Canadian group, the body of evidence used by the CTT has a number of weaknesses and inconsistencies which should not go unrecognised.

One of the major gripes had by the Canadian group concerns the dosages of statins used in the trials. Specifically, studies compared very different dosages e.g. 10 mg versus 80 mg of atorvastatin (Lipitor). However, in clinical practice, in people deemed to be at high risk of cardiovascular disease, rarely will a low dose of 10 mg of atorvastatin be used. It is much more common for an individual to be, say, on a dose of 40 mg, and the question might then be whether or not to raise the dose to 80 mg per day. In other words, in the real world, doctors will usually be debating whether or not to use moderate or high doses of statin. These decisions, it is argued, are not properly informed by data in which high dosages have been compared with very low (and often unrealistic) dosages of statins.

Another problem cited by the Canadian group is that in many of the studies used by the CTT, individuals started out with relatively high levels of LDL-cholesterol. We cannot tell from this data what the impact would be on individuals with normal or lower-than-normal cholesterol levels would be. So, it is not correct to assume that the benefits seen in people with higher cholesterol will extend into those with normal or low levels.

The Canadian group goes on to estimate the likely benefit of increasing atorvastatin dosing from 40 to 80 mg. They calculate that the likely reduction in ‘clinical events’ such as heart attacks and stroke to be about 2 per cent (small). Of course, as the they point out, significant increases in statin dosage will likely bring with them a significant increase in the number of adverse effects including muscle pain, fatigue, liver damage and kidney damage.

In reference to the idea of raising statin dosage the authors conclude:

Accordingly, whether net benefit would be demonstrable cannot be assumed. It follows that definitive evidence supporting maximal lowering of LDL-C or maximal dose of statins is still lacking and guidelines, if they are to be evidence-based, should acknowledge this uncertainty.

Back in February, I wrote a critique of the CTT’s latest offering and their recommendation that statins should be put in the water supply (almost). It seems to me that the CTT goes to great lengths to put a positive spin on whatever data they can dredge, and this might have something to do with the conflicts of interest to be found in members of the group.


1. Sniderman A, et al. Is lower and lower better and better? A re-evaluation of the evidence from the Cholesterol Treatment Trialists’ Collaboration meta-analysis for low-density lipoprotein lowering. J Clin Lipidol 2012;6(4):303-9

2. Cannon CP, et al. Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes. N Engl J Med. 2004;350:1495–504

3. La Rosa JC, et al. Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease. N Engl J Med. 2005;352:1425–35

4. Pedersen TR, et al. High-Dose Atorvastatin vs Usual-Dose Simvastatin for Secondary Prevention After Myocardial Infarction: The IDEAL Study: A Randomized Controlled Trial. JAMA. 2005;294:2437–45

5. de Lemos JA, et al. Early Intensive vs a Delayed Conservative Simvastatin Strategy in Patients With Acute Coronary Syndromes: Phase Z of the A to Z Trial. JAMA. 2004;292:1307–16

6. Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12 064 survivors of myocardial infarction: a double-blind randomised trial. Lancet. 2010;376:1658–69

7. Cholesterol Treatment Trialists’ (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. The Lancet epub 17th May 2012

8. Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-81

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