Cardiovascular disease (heart attack and stroke) causes the most deaths in Western countries overall and the vast majority of premature deaths.
By Ian Hamilton-Craig, Griffith University
Drugs known as statins have been the cornerstone of how we treat people at risk of such deaths, and they’ve made a huge difference to survival rates.
Statins are the most widely prescribed medication in Australia, where 45,600 people (31% of all deaths) died of heart attacks and strokes in 2011. In 2010-11, statins were taken by an estimated 2.6 million Australians (mean age 67 years, with mean age for starting treatment 58 years).
Risk factors for heart disease include age, being male, smoking cigarettes, high blood cholesterol, diabetes, and high blood pressure. Rates of cardiovascular disease have fallen with improved control of these risk factors through dietary changes and drug treatment, including statins; between 1991 and 2002, deaths from cardiovascular disease fell by 36% in men and 34% in women.
Heart health and cholesterol
Statins work by lowering blood cholesterol levels, especially the levels of low-density lipoprotein (LDL).
A small amount of low-density lipoprotein is essential for life as it delivers cholesterol to tissues, which use it to maintain cell membrane structure, to synthesise hormones, and to allow cells to proliferate. But too much of it is bad because it promotes the formation of plaques in coronary arteries.
Indeed, high blood levels of LDL cholesterol are directly correlated with increased rates of coronary disease (heart attack, angina, heart failure, and sudden death) and stroke.
When LDL cholesterol accumulates inside the walls of the arteries to the heart and brain, it forms plaques and results in atherosclerosis (narrowing from plaque formation). Atherosclerotic plaques gradually enlarge and narrow the artery. If they rupture, blood flow to the heart or brain can suddenly be blocked, resulting in heart attack or stroke.
Plaques form when LDL cholesterol accumulates inside the walls of the arteries to the heart and brain. (Leo Reynolds)
High levels of LDL allow cholesterol accumulation inside cells, starting (or continuing) the process of plaque build up. Statins reduce the risk of cardiovascular disease by reducing LDL levels and improve survival for people at high risk of cardiovascular disease.
They reduce the liver’s synthesis of cholesterol, and in response, the liver up-regulates its LDL receptors, restoring cholesterol levels in the liver, and reducing blood levels of LDL.
Many things can affect blood LDL cholesterol levels, including genetic disorders. Familial hypercholesterolaemia, for instance, results in reduced LDL receptor function and high levels of LDL cholesterol. This, in turn, increases the rate of coronary disease.
A 2008 UK study found the death rate in people with familial hypercholesterolaemia was 37% times higher before statins were available.
They are now used to treat people at high risk of heart attacks and strokes based on the results of many clinical trials showing reduced risk with statin treatment.
The benefits of statins include fewer heart attacks and strokes, and improved survival for people at highest cardiovascular risk.
A 2012 study of 27 randomised control trials for statins showed a 24% reduction in relative risk per unit of LDL (the difference in rates of cardiovascular disease between groups receiving statins and control groups).
The absolute risk reduction (difference in absolute rate of cardiovascular disease between the statin and control groups) is, naturally, greater in those at higher baseline risk. You’ll recall that the baseline risk is affected by such factors as age, gender, smoking habits, blood pressure, cholesterol levels and whether you have diabetes.
Statins also reduce the risk of cardiovascular disease in people at very low risk (less than 10%). But even though they may benefit from statins, whether these low-risk people should take them is a matter for health economists and ethicists to consider.
Statin prescriptions in Australia are only reimbursed for those at highest cardiovascular risk, independent of blood cholesterol levels.
Statins' side effects
All medicines have potential side effects and statins are no exception. That’s why there are guidelines for statin use.
Whether these low-risk people should take statins is a matter for health economists and ethicists to consider. (AJ Cann)
One significant side effect of statins is the risk of developing diabetes, especially if you are overweight. In the approximately 250,000 people treated with the drugs in 135 randomised trials, there was a 9% increased risk of developing diabetes compared to the rest of the population.
But this increased risk is outweighed by the benefits statins have for heart health in high-risk people.
The authors of a meta-analysis of 27 clinical trials of statins found the risk of cancer was not increased. They also found that statins were well tolerated, with no evidence of increased muscle side effects, and only a slight increase in liver enzymes (transminases) that can indicate it’s damaged.
These data differ from the “real world” experience, as a study 7,924 people treated with high dose statins showed. In this study, 10.5% of people taking statins complained of muscle symptoms (pain, aches, stiffness, weakness, fatigue, cramping and tenderness), usually within a month after starting to take the drugs.
These symptoms were severe enough to prevent moderate exercise in 38% of the people in the study, and 4% were unable to work, or were confined to bed.
Risk factors for developing muscle symptoms included a history of muscle pain with other similar therapy (ten times more likely), unexplained cramps (four times more likely), a family history of muscle symptoms (twice as likely), and low thyroid activity (70% more likely).
People at most risk of side effects are the elderly (aged over 75 years) because they metabolise the drug less efficiently, so there’s a higher level of statins in their blood, predisposing them to muscle toxicity. People with lean muscle mass, and risk factors for muscle symptoms outlined above are also more likely to suffer these side effects.
Other people also at risk are those taking drugs that may raise blood levels of certain statins, liver or kidney disease, taking high-dose statins, and those undertaking high levels of physical exercise (because it predisposes them to getting the muscle symptoms).
For these people, lower doses of statins with close monitoring may be the best way to proceed, or they may need to try alternative therapies.
Statins have made a big difference to evidence-based preventative medicine. And they have improved the quality of life for many people who would have otherwise suffered debilitating cardiovascular disease.
Ian Hamilton-Craig is a current member of Lipid Advisory Boards for Merck, Sharp & Dohme ( for ezetimibe, a non-statin cholesterol absorption inhibitor), Abbott (for fenofibrate, a non-statin fibrate) and Amgen (for AMG-145, a non-statin PCSK9 inhibitor).