May 17th, 2012

Large Meta-Analysis Finds Statins Effective in Low-Risk Patients

A very large meta-analysis provides strong evidence that the relative reduction in vascular risk with statins is at least as great in low-risk patients as in high-risk patients. The finding, write the authors, provides evidence that expansion of guidelines to lower-risk populations should be considered.

In their paper in the Lancet, the Cholesterol Treatment Trialists’ (CTT) Collaborators analyzed data from 134,537 patients in trials comparing statins with control therapy and 39,612 patients in trials comparing low- and high-dose statins. They examined the impact of statin therapy according to the baseline 5-year risk for a major vascular event on control therapy. Statin therapy caused a consistent reduction in the relative risk for major vascular events and all-cause mortality independent of other factors, including age, sex, baseline LDL cholesterol, or established CV disease.

Here are the rate ratios for major vascular events across five levels of risk at baseline (note that 1 mmol of LDL cholesterol is equivalent to about 39 mg/dL of LDL):

        5-Year Risk           Rate ratio per 1.0 mmol/L of LDL reduction

  • <5%                          0·62 [99% CI 0·47–0·81]
  • ≥5% to <10%          0·69 [99% CI 0·60–0·79]
  • ≥10% to <20%        0·79 [99% CI 0·74–0·85]
  • ≥20% to <30%        0·81 [99% CI 0·77–0·86]
  •  ≥30%                       0·79 [99% CI 0·74–0·84]

The meta-analysis found no evidence for harm associated with statin therapy, including cancer or other nonvascular mortality.

The authors note that current guidelines do not recommend statin therapy for people in the lowest two risk categories in the study, who are expected to have a 5-year event rate lower than 10%. As generic statins are highly cost-effective, they write, the study “suggests that these guidelines might need to be reconsidered.”

In an accompanying comment, Shah Ebrahim and Juan Casas ask whether everyone over the age of 50 should take statins. They calculate that, in the U.K., adoption of a threshold of 10% would classify 83% of men over age 50 and 56% of women over age 60 as needing statins.

2 Responses to “Large Meta-Analysis Finds Statins Effective in Low-Risk Patients”

  1. Uffe Ravnskov, MD, PhD says:

    I think that the crucial question for most people is: Can I prolong my life by statin treatment and is it without any risk? Let me try to answer these questions.
    From table 3 in the Lancet paper it is possible to calculate that the chance to be alive after five years for people without vascular disease and whose 5-year risk of a major vascular event lies between 10% and 20%, is 89.9%. If they take a statin every day they can increase their chance to 90.7%.
    For the highest risk group, those with vascular disease and whose 5-year risk is 30%, the corresponding figures are 74.05% and 76.7%.
    For those with a five year risk less than 10%, their chance to survive is the same, whether they are on statin treatment or not and whether they have a vascular disease or not.
    Do this small benefit really exceed any known hazards of statin therapy, as the authors wrote? I doubt. Two years ago independent authors reported the outcome after statin treatment in more than 200,000 patients treated by the general practitioners ( More than four per cent had moderate or serious adverse effects from the muscles, liver, kidneys or eyes. These numbers may even have been underestimated, because liver damage was recorded only if the alanine transaminase concentration was more than three times higher than the upper limit of normal, and muscle damage only if the creatine kinase concentration was four or more times higher than the upper limit of normal. Furthermore they had not examined the frequency of diabetes, impotency or cerebral symptoms, which have been shown to be risks by other investigators.

  2. Neville Wilson, M.B., Ch.B., D.Fam. Med., M.Sc., D.Obs (COG) SA., B.A. says:

    In a meta-analysis of 11 RCT involving 65000 persons, the effects of statins on all cause mortality was tested in a comparison with placebo,producing a result of insignificant difference between the 2 groups.(K.K.Ray etal)
    In a study of 17,800 participants, after excluding 1,500 for various reasons, the number of all cause deaths was 2.2% in the rosuvastatin group and 2.8% in the placebo group.(JUPITER) with figures for cardiovascular mortality witheld. Hardly a convincing benefit.
    Results from the major statin trials will show a benefit unrelated to LDL lowering, which does not support the rationale for expanding the guidelines to lower LDL targets. Mortality benefits, where shown, were not due to LDL lowering !
    In others,with dose comparisons, like TNT, mortality benefits were not convincing, with 5.6% for low dose statin and 5.7% for high dose (80mg) statin. So, no increase in lifespan with the higher dose was demonstrated.
    Also, the high drop out rate in many trials is suggestive of the high incidence of under reported and under estimated adverse events from statin use. 23% of participants stopped their drugs within 6 years (ALLHAT) and 30% within 2 years (PROVE-IT).
    If any recommendations are to be made regarding future guidelines, it should be the scrapping of LDL and total cholesterol targets.