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Prescribing Advice for GPs

An NHS Prescribing Advisers' Blog

Statin Tolerability

Following the PCT recommendation to review prescribing of Atorvastatin 10mg and consider switching to Simvastatin 40mg, there have been several queries regarding the comparative tolerability of Simvastatin.

The CURVES Study1 compared the efficacy and tolerability of five statins, including Simvastatin and Atorvastatin. It found that "All reductase inhibitors studied had similar tolerability". This study is often quoted when comparing the relative efficacy of statins at differing strengths.

Similarly, the ASAP Study2 compared aggressive doses of Atorvastatin and Simvastatin (80mg vs 40mg) and found that "Both drugs were equally well tolerated".

Finally, the Heart Protection Study3 was a randomised, double blind trial that compared Simvastatin 40mg to placebo, with or without additional antioxidant vitamin supplementation. Over the period of the study (average 5 years) a third of patients in the Simvastatin arm and a third of patients in the placebo arm experienced muscle pain or weakness. Only 0.5% of these subsequenlty stopped the study medication (active or placebo).

Action: Clinical studies have shown that Simvastatin is equally well tolerated as other statins and the HPS Study has shown it is as well tolerated as placebo. Tolerability of Simvastatin should not be an issue when considering a switch from Atorvastatin 10mg to Simvastatin 40mg. Following the switch any patients do not tolerate Simvastatin can be switched back without problem.


  1. Jones P, et al. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). American Journal of Cardiology 1998; 81: 582-587.
  2. Smilde TJ, et al. Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial. Lancet 2001; 357: 577-581.
  3. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 7-22M

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