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Statin safety: a perspective

Systematic review
Results
Rhabdomyolysis
Myopathy
Minor muscle pain
Liver failure
Stroke
Peripheral neuropathy
Cognitive function
Comment

Bandolier, in print and electronically, has looked at the issue of major harm associated with statins. It is important, because very many people take statins, and even rare events mount up in this circumstance. A new systematic review [1] provides some perspective, and Bandolier has attempted to use a version of the Paling Perspective Scale of risk to try and extend that perspective.


Systematic review

The systematic review sought cohort studies, randomised placebo controlled trials of 2-5 years duration looking for reduction in cardiovascular disease events, notifications of adverse events to regulatory authorities, and case reports that investigated statins and particular adverse events. These included rhabdomyolysis, myopathy, liver failure, stroke, and peripheral neuropathy. It then sought to estimate the statin-specific risk as incidence per 100,000 person years.


Results

What follows is a brief description of the results, limited to statins (simvastatin, atorvastatin, pravastatin) other than cerivastatin, and omitting discussion of fibrates.


Rhabdomyolysis

Cohort studies indicate a rate of 3.4 (1.6 to 6.5)/100,000 person years (1 in 29,000 per year) from cohort studies, supported by RCTs and notifications. Mortality with rhabdomyolysis is about 10%, giving a statin-specific death rate of about 1 in 300,000 per year. This is about 15 times less likely than dying in a car accident in a year.


Myopathy

Statin-specific myopathy from cohort studies, supported by RCTs was about 11 (4-27)/100,000 person years, a rate of 1 in 9,100 per year. It is reversible on stopping statin.


Minor muscle pain

This was no more common with statin than with placebo in RCTs, but was common, at about 5,000/100,000 person years with statin and placebo. This complaint affected about 1 in 20 of the population in the trials, irrespective of therapy.


Liver failure

The estimated risk of liver failure of someone taking statins was 0.5 per 100,000 person years, or 1 in 200,000 per year. This is about the same as people not taking statins.


Stroke

Stroke was no more common in people taking statins as not, though the rate of haemorrhagic stroke may have been higher. The advice was not to use cholesterol-lowering drugs in people who had had a haemorrhagic stroke.


Peripheral neuropathy

Cohort studies and RCTs indicated higher rates of reversible peripheral neuropathy with statins, with a statin-specific risk of about 12/100,000 person years, or a rate in 1 in 8,300 per year.


Cognitive function

No greater decline in cognitive function with statin than not.



Figure 1: Statin adverse events set in Paling Perspective Scale, with US deaths, 2002, as perspective






Comment

Figure 1 tries to summarise these results in one picture, with markers of death rates from various causes in the USA in 2002 for comparison. Death from rhabdomyolysis with statin was far less common than many other causes of death, including heart disease and accidents. It would be about as likely as dying from a gunshot wound.

The figure is another use of one of the forms of the Paling Perspective Scale. Bandolier has used deaths for comparison, which is a bit unfair for myopathy and peripheral neuropathy, which are reversible on stopping statin. It would be better to have other comparators, but we are still working on that.

Because the events were by their nature rare, there was not always a large number, so to some extent the actual event rates are best guesses. For the most part, these were reasonable and conservative.

Equally interesting is why about half of people prescribed a statin stop taking it by about a year. Anecdotally, Bandolier hears that diarrhoea is responsible, but can find no studies to support this, or much at all on common adverse events with statins. Does anyone out there know better?

Reference:

  1. 1 M Law, AR Rudnicka. Statin safety: a systematic review. American Journal of Cardiology 2006 97 (Suppl): 52C-60C.

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