statin safety

There have been a slew of articles in the literature in the past year on the harmful effects of statins. A recent study-level network meta-analysis was reported, incorporating 135 randomized controlled trials with 250K participants to assess the reported adverse effects (note that some of these effects could have been under-reported, such as myalgias, given the relative frequency of such in many of our clinical practices but their low numbers) -- see statin tolerability circ cardiol qual 2013 in dropbox, or DOI: 10.1161/CIRCOUTCOMES.111.000071. 

 The findings:

                --no difference between individual statins and controls for: myalgias (subjective muscle pain), creatine kinase elevations (varied in studies from 3x to 10x more than baseline), cancer, or discontinuations because of adverse events. Likelihood of rhabdomyolysis small and no diff from controls.

                --overall 9% higher likelihood of developing diabetes

                --51% higher likelihood of developing transaminitis (ALT or AST >3x baseline, though note that this is not a clinical marker only a biochemical one)

                --simvastatin and pravastatin best tolerated, higher doses of atorvastatin and rosuvastatin less tolerated

                --higher dose simvastatin (>40mg/d) assoc with more marked increase in CK elevations (OR 4.14)

Some specifics:

                --myalgias: in the larger analysis of all studies, found in 2% of participants, no diff between statins

                --transaminitis: 1% of participants. Atorva the worst in dose-response fashion, with OR 5.25 if >40mg/d.  fluvastatin pretty bad, but no one uses this anymore….

                --CK elevations: 0.6% of individuals. Worst with high-dose simva (though interesting that myalgias in this group were not significantly different from controls and actually had a trend to be 28% less than controls…)

                --diabetes: overall 9% increased risk, though worse for high-dose rosuvastatin (16%) in the placebo-controlled direct trials, but no individual statin difference in the overall network analysis.

                --simva and prava were best in the combined outcomes (includes discontinuations from combo of adverse effects, myalgia, transaminitis and CK elevation)

                --pitavastatin recently approved by FDA (have never used it myself), but in general seems to be worse than the others overall.

The background here is that statins are dramatically effective in reducing clinical cardiac/cerebrovascular events, in the elderly, in women, in patients with diabetes, with relative risk reductions in the 25-30% range (even in patients with diabetes felt by their endocrinologists not to need statins  because their cholesterol levels were “okay”). Of course the absolute risk reduction depends on the risk status of the cohort involved,but recent meta-analyses have shown pretty conclusively that statins are beneficial even in primary prevention and even if some cases of diabetes develop) -- see statins diabetes jupiter lancet 2012 in dropbox, or Lancet 2012; 380: 565–71 for Jupiter study with rosuvastatin, the worst one in the above meta-analysis, and argument that cardiovasc benefits exceed diabetes risk. Overall, there do seem to be some differences between the statins, with pravastatin and simvastatin having the fewest adverse effects (I was a bit surprised here, since some earlier individual studies found worse problems with simvastatin vs atorvastatin,  which reinforces the utility of these larger analyses).