Saturday, July 23, 2005

Atorvastatin in end stage renal disease

This week's New England Journal of Medicine reported a study of atorvastatin treatment for patients with type 2 diabetes undergoing hemodialysis. There was no difference from placebo in the primary composite endpoint, a relative risk of .82 for combined cardiac events, and a relative risk of 2.03 for fatal stroke. There was no difference in non-fatal stroke or all cause mortality.

The media are already hyping this study, citing the “surprising” findings and highlighting a “two fold increase in deadly stroke” due to the statin. So, let’s take a moment for a sober assessment.

The results are disappointing, but how surprising, really? The attributes of the study population suggest that the principal dyslipidemia was the metabolic syndrome, characterized by high triglycerides, low HDL, and presumably small dense LDL particles. (The mean pre-treatment LDL cholesterol was 126 and the mean triglyceride level was around 265). It has long been known that statins are of limited effectiveness in treating the metabolic syndrome. Multiple other atherogenic factors are known to be associated with end stage renal disease including hypercoagulability, elevated levels of lipoprotein (a), elevated homocysteine, elevated angiotensin II, and disturbances in calcium and phosphate metabolism. Such factors are not mitigated by statin treatment. We would not expect LDLC to be the principal player in the vast atherogenic milieu of ESRD.

The finding regarding fatal stroke is unexplained. The authors point out in the discussion section of the paper that it could be due to chance. True to form, the popular media have cited only the more sensational increase in relative risk. The actual absolute excess in stroke mortality, though not trivial, was somewhat less impressive (2%, number needed to harm 50).

An essential tenet of evidence-based medicine is critical appraisal the literature, something we don't usually find in the lay press.

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