Fillers POEM

High dose statins lower C reactive protein

BMJ 2005; 330 doi: (Published 21 April 2005) Cite this as: BMJ 2005;330:0-e

Question Is a lower C reactive protein level after aggressive treatment with statins associated with a lower risk of recurrent coronary events?

Synopsis This is a post hoc analysis of a randomised trial that compared atorvastatin (Lipitor) 80 mg with pravastatin (Pravachol) 40 mg in 4162 patients with acute coronary syndrome. Of those, 3745 had low density lipoprotein (LDL) and C reactive protein (CRP) levels measured 30 days after hospital discharge. There was a linear relationship between the reduction in LDL and the risk of recurrent coronary events (cardiovascular death or non-fatal myocardial infarction) and a similar relationship between the reduction in CRP and the risk of recurrent coronary events. The effects of LDL and CRP were statistically independent. Patients were divided into quartiles by their final CRP; the lowest quartile (< 0.9 mg/l) had a relative risk of 1.0, compared with 1.5 for those with a CRP level between 0.9 and 4.2 mg/l, and 1.9 for those with a CRP level greater than 4.2 mg/l. The authors did a variety of subgroup analyses. The most relevant are those for patients who wouldn't otherwise be prescribed a statin; that is, those with LDL < 70. In this group, the difference in recurrent coronary events was statistically significant, but clinically small: 3.1 v 2.4 events per 100 person years, corresponding to a number needed to treat of 140 per year. Another study in the same issue (N Engl J Med 2005;352: 29-38 found that reduction in CRP levels by statins was associated with reductions in the extent of lesions as measured by endovascular ultrasonography. However, only a very high dose of statin (atorvastatin 80 mg) lowered the CRP at all.

Bottom line This post hoc analysis provides support to the hypothesis that statins have an effect on secondary prevention of cardiovascular disease that extends beyond their ability to lower low density lipoprotein levels. However, the absolute benefit is very small in patients with a low LDL who otherwise wouldn't be candidates for statins, even in this very high risk population of patients with acute coronary syndrome. We now need prospective randomised trials of primary prevention in patients who wouldn't otherwise be candidates for statins, comparing this approach to modifying inflammation with other candidate drugs. Such a trial (JUPITER) is underway. Until then, and until the balance of benefits and harms of screening for CRP is fully explored, we should not extend this policy of CRP screening to all of our patients, and certainly not to those without known coronary disease.

Level of evidence 2c (see“Outcomes” research; ecological studies

Ridker PM, Cannon CP, Morrow D, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005;352: 20-8

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  • * Patient-Oriented Evidence that Matters. See editorial BMJ 2002;325: 983

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