A systemic review of statin safety should finally put to rest inaccurate reports that statins currently on the market are not safe. It is probable that the beginning of these reports dates back to the withdrawal of cerivastatin (Baycol)from worldwide markets in August 2001 because of alarming reports that Baycol had an 80-fold increased reporting rate of rhabdomyolysis compared with other statins available at the time. This review of issues regarding the safety of statins currently available is based on data from a wide variety of sources including prospective cohort studies, placebo controlled trials, voluntary notifications of drug-related adverse events to national regulatory authorities, and published case reports.
It is of course important to recognise that although statins are safe as monotherapy, that when other medications are taken that safety can become compromised. Thus a review of muscle toxicity, myopathies and creatine kinase elevations found them to be essentially random, transient, or uncommon. with a slightly higher incidence of minor muscle pain compared with placebo. A number of potential concomitant medications have been identified that do present risk and warrant lower statin doses due to the heightened risk of myopathy including treatment with gemfibrozil or other fibrates, grapefruit juice and other CYP3A4 inhibitors, ritonavir and other HIV protease inhibitors, erythromycin and other macrolide antibiotics, azole antifungals, and other drugs such as the antidepressant nefazodone.
Although a low incidence of elevated liver transaminases occurred in a dose related manner in some patients, reversal occurred with continued treatment, reduced treatment, or discontinuation. Liver toxicity, if it exists at all, was judged to be exceedingly rare. Gall bladder disorders were found to be lower in patients receiving statins compared to a placebo. No evidence was found for an increase in renal failure or chronic renal failure in those taking a statin, and there was actually a significantly lower rate of decline in glomerular filtration rate in patients taking statins compared to controls.
Some evidence was found that although statins reduce the risk of stroke overall (largely acute ischemic stroke) there is some evidence of an increased risk of hemorrhagic stroke but that effect could be due to cholesterol reduction by any means and not specifically due to statin treatment. A low incidence of peripheral neuropathy was found, resolving on statin discontinuation. Cognitive decline in elderly patients was comparable between statin treatment and placebo.
In conclusion, the review of available data concluded there is a very low absolute risk of statin-associated toxicity and given the very considerable risk of cardiovascular events in patients being treated with a statin, it would not be prudent to withold statin treatment fearing adverse events. Caution would be appropriate in witholding or discontinuing statins for patients receiving medications that can increase circulating statin levels via pharmacokinetic reactions as identified above.
Coronary heart disease (CHD) is the leading cause of death among US residents, responsible for more than 650,000 deaths annually, 500,000 recurrent myocardial infarction (MI, heart attack) cases, and approximately 700,000 new cases of myocardial infarction each year. Statins are integral to reduce this incidence and several landmark trials have demonstrated a 23% to 37% reduction in relative risk and coronary mortality because of their ability to modify lipid levels as well as inflammatory, thrombotic, and other mechanisms of atherosclerosis.
Although serious muscle toxicity with currently marketed statins is very rare, ongoing patient interaction to monitor myotoxicity on the continuum from mild myalgias to rhamdomyolysis is essential since interaction with other medications is known, has been defined, and does present risk.
Current monitoring of liver enzymes should be continued, although there is no need to discontinue statin therapy for an isolated asymptomatic transaminase level 1-3 times the upper level of normal, and if routine evaluation is greater than 3 times the upper limit of normal the test should be repeated and, if still elevated, other causes ruled out. Healthcare professionals should be alert to patient reports of jaundice, malaise, fatigue indicating hepatotoxicity.
A baseline renal function should be done for patients about to be placed on statin therapy, however several lines of evidence indicate that statins may have a renoprotective effect.
Since the potential risk of peripheral neuropathy is very small, if it exists at all, it is reasonable to rule out secondary causes such as diabetes, alcohol abuse vitamin B12, renal insufficiency and hypothyroidism. There is some evidence that statins can reduce the rate of cognitive decline in patients with mild to moderate Alzheimer's disease.
The benefit/risk ratio for statin therapy in averting myocardial infarction (heart attack) and cerebral infarction (stroke) is very high.
Since the first major clinical trials established the efficacy of statin therapy in the prevention of coronary heart disease it has also been noted that the therapy reduces the risk of stroke. It has been reported that a risk reduction of 28%
of ischemic stroke with no apparent difference in the risk of hemorrhagic stroke.
Further investigation of high dose statin therapy in patients without coronary heart disease but a history of stroke or transient ischemic attack (TIA) as reported at the International Stroke Conference, February 7-8, 2007, the SPARCL study, has established efficacy in reducing the risk of stroke. On a 4.9 year follow-up patients with a greater than 50% reduction of LDL-cholesterol had a relative reduction in risk of stroke of 31%.
A study in the Netherlands on folate deficient patients aged 50 to 70 years treated with folic acid daily for three years showed an association with significantly less decline in global cognitive function, memory, information processing and sensimotor speed.
Due to the increasing number of trials aimed at plaque reversal by increasing HDL-cholesterol as well as the disappointing termination of the torcetrapib trials an emerging interest in visualizing arterial plaque with newer technological methods promises to place future trials on a firmer basis of evaluation.
A multidisciplinary group has developed new guidelines for evaluating carotid plaque in the general population not yet exhibiting symptoms. Such guidelines could help avert stroke before it happens.
Implanted radioactive seeds for early stage prostate cancer have been shown to have an excellent outcome.
Researchers have claimed that adding 2000 IU of Vitamin D3 daily to an individual's diet could lower the risk of breast cancer by half and colorectal cancer by two thirds. Further study of this claim is needed.
Increasing circulating Vitamin D3 levels improves survival rates in patients after surgery for early stage lung cancer.
Increased circulating Vitamin D3 levels have been associated with significantly less risk of developing multiple sclerosis.
Intake of Vitamin D3 is needed to achieve new guidelines for optimal circulating Vitamin D3 levels.
The Rush Institute in Chicago has published data showing that an adequete supply of Niacin in the diet can cut the incidence of Alzheimer's disease by as much as 70%.
Debate continues on how low LDL-cholesterol levels should be taken.
Research continues on finding new drug candidates to lower LDL-cholesterol.
Raising HDL-cholesterol is still a major objective despite setbacks.
For the first time teeth grown from single cells in culture have been used successfully to replace natural teeth in mice. Is this the beginning of hope for those wearing dentures?