Skip to Content

How statins may work to reduce decline
in physical and mental function

Statins (HMG-CoA reductase inhibitors) are a class of drug which is best known for its ability to lower cholesterol. They work by inhibiting a pathway responsible for producing cholesterol (the mevalonate pathway). This interrupts an enzyme in the liver (HMG-CoA reductase) that is essential in the production of cholesterol and other lipids (particularly isoprenoids). By interrupting this pathway it is thought that statins may reduce decline in physical and mental function as well as reducing the incidence of heart disease, stroke and dementia.

Statins and healthy ageing

Current thinking on statin therapy

Evidence for the lipid lowering effect of statins has come from many different clinical trials over the last 30 years.

Statins are commonly prescribed for lowering circulating LDL cholesterol levels in the blood by blocking a key liver enzyme involved in cholesterol synthesis.

  • Reductions in circulating LDL cholesterol decrease the incidence of cardiovascular disease including myocardial infarction and stroke.
  • Approximately 18-55% reductions in LDL cholesterol are achieved with statin therapy.
  • Modest reductions in circulating triglycerides (7-30%) and increases in HDL cholesterol (5-15%) are also achieved with statin therapy.

Not all people with high cholesterol levels need statin therapy. The absolute benefit of statin therapy is greatest in people who already have cardiovascular disease or are at high risk of developing it.

  • Statins are recommended for all patients with established cardiovascular disease to prevent subsequent cardiovascular events (secondary prevention). Statins are also recommended for people who have a high risk of developing cardiovascular disease (primary prevention), such as people aged over 60 years with diabetes, or people with moderate or severe chronic kidney disease.
  • Clinical trials have shown that those with established cardiovascular disease or at high risk of cardiovascular disease have a significantly reduced risk of subsequent major vascular events and death when taking a statin. However, most of the people studied in these trials were middle-aged.

Some people experience adverse symptoms with statins. The chance of developing side effects can vary greatly between people. The side effects are usually mild and temporary.

  • The most common side effect of statin therapy is muscle and/or joint pain. Mild muscle pain (myalgia) occurs in 5-15% of people taking a statin.
  • Some people report “foggy thinking”, confusion or memory loss on statin therapy. This is reversible on statin discontinuation.
  • There is a small increase in the risk of developing type 2 diabetes while taking statin therapy.
  • Statin therapy slightly increases the risk of developing elevated liver enzymes.
    The likelihood of experiencing adverse effects from any drug is increased in older people.
    Statins also potentially have a number of cholesterol independent effects including a moderately powerful anti-inflammatory action. Little is known about the clinical impact of these effects.

Uncertainty surrounding statin therapy in clinical practice

Very few people aged over 70 years have been included in clinical trials of statins for primary prevention of cardiovascular disease.

Therefore, there is uncertainty about the balance of risk and benefits of statins therapy in healthy older people. We do not have the evidence to answer the following questions:

  • Is statin therapy cost effective in healthy elderly people?
  • Can statins prevent a first heart attack or stroke in older people?
  • Can statins improve healthy life expectancy in older people?
  • Do statins impact on the day to day physical function of older people?
  • Are the frequency and/or severity of adverse reactions to statins higher in older people?
  • Is the risk of developing diabetes higher in older people?
  • Can statins prevent dementia?
  • Are statins useful to treat Alzheimer’s disease?

STAREE to answer public and clinical uncertainties around statin therapy

Guidelines released recently in the US and the UK recommend a more aggressive approach for statin use in people under age 75, which will triple the number of people in these countries who are eligible for statin therapy, especially in those aged between 70-75, yet overall the balance of risks and benefits remains unclear in older people.

Some media reports claim that statins are the new “wonder drug”, and others report negative commentary about side effects, which can strongly influence some patients about commencing or continuing their statin therapy.

The placebo controlled trial of statin, STAREE (Statins in Reducing Events in the Elderly), will provide the evidence required to determine whether or not statin therapy should be taken routinely by healthy people aged over 70 years.

History of statins

1900s German pathologist Virchow noticed the artery walls of patient contained a substance identified as cholesterol
1950s Compactin, the first statin was discovered in Japan.
1970s Framingham study showed links between cholesterol and heart disease.
1978 Merck Research Laboratories discovered Lovastatin (the first commercially available statin).
1984 NIH conclude that lowering elevated LDL cholesterol with diet and drugs would reduce risk of CHD.
1987 Lovastatin becomes available by prescription
1990–1994 4S trial shows unequivocally a reduction of mortality with simvastin (men and women aged 35-70 years).
1995–1998 5 clinical outcome trials show a reduction of coronary events with very few adverse effects
2000 Heart Protection study confirms safety of statins in five year trial of 20,000 patients (men and women aged 40-80 years; most participants aged under 70).
2013 US guidelines on statin use change to recommend statin use in those with a 7.5% or higher 10 year risk of cardiovascular disease in those aged 40-75 years. No guidance for those aged over 75.
2014 The UK National Institute for Health and Care Excellence (NICE) draft new guidelines on statin use, which recommends primary prevention statin therapy for those with an increased risk of coronary vascular disease, up to age 84.
2015 Launch of the first primary preventive trial of statins in those aged over 70 in Australia – the STAREE trial.