Statins are a class of drugs commonly used to lower cholesterol levels and help prevent cardiovascular disease. Since their introduction in the late 1980s, their prescription has steadily increased, and with this concerns over how widely dispensed they have become. Whilst generally accepted as beneficial in the secondary prevention of cardiovascular disease, increased use of statins in primary prevention has raised questions over the balance between potential benefits and unintended harmful effects. In a recent study in BMC Medicine, Shah Ebrahim and colleagues at the London School of Hygiene and Tropical Medicine, UK, carried out a systematic review and meta-analysis of observational studies in the general population, finding that the benefits of statins did in general outweigh the risks. We asked cardiologist Michael Blaha from the Johns Hopkins School of Medicine, USA, for his thoughts on the statins debate in light of recent studies.
How widely used are statins in the general population and how has their use changed over the years in the primary and secondary prevention of cardiovascular disease?
Although there is regional and practice-level variability, in general statins are widely used in the general population. As guidelines have changed and performance metrics have been added, statin use is now nearly universal in the secondary prevention of heart attacks and atherosclerotic stroke. There still remains a great deal of controversy about statin use in primary prevention. However, for the most part, clinicians have felt increasingly comfortable giving statins to a wide variety of patients in primary prevention, including those with high global risk, those with very high cholesterol levels, and younger patients with multiple risk factors. While it is tough to get definitive numbers on this, some estimates are that there are 30 million statin users in the United States and up to 200 million users worldwide.
What have been the major concerns around the use of statins in the primary prevention of cardiovascular disease?
We have never seen a drug class quite like statins before. Here we have a drug that reduces cardiovascular risk in nearly everybody, is relatively cheap, and in general has few side effects. Who do you give such a drug to? I am not sure we have had to deal with such a question before. Opinions have varied from everybody (it should be in the water) to a very focused group of high risk patients. Once you start talking about giving a drug to everybody, even uncommon and reversible side effects can become a major issue.
The recent study in BMC Medicine suggests that the overall risk of the observed harmful unintended effects of statins is very small compared to their beneficial effects. How do you think these, and similar findings, will impact clinical practice in the US?
The excellent study in BMC Medicine comes on the heels of several interesting recent analyses showing that – in general – the benefits of statins outweigh the risks. The question becomes, while true on the average, is this calculus true for all individuals? The answer of course is no. Some individuals will receive a net harm from statins, many will receive a net benefit. The question then becomes how we can best tell who stands the most to gain from statins.
The American College of Cardiology/American Heart Association (ACC/AHA) guideline recommends increased use of statins among a wider section of the population. What impact do you think this will have on the healthcare system?
I think that the new guidelines will increase statin use. In general, this is a good thing. Researchers now have to figure out if the new ACC/AHA guidelines are giving statins to the right people. This will determine the net impact on the healthcare system and its cost efficiency.
What are the current challenges and future directions in the pharmacological prevention of cardiovascular disease?
To me, it is time to shift part of our attention away from searching for new drugs, and take a larger population and healthcare system-based perspective. We now have great drugs that reduce risk. We have the ammunition. Now the critical question is how do you allocate such a resource, how do you measure the net health outcome effect, how do you gauge cost effectiveness? More than ever, we need health outcomes and health policy researchers to carefully examine these questions. Soon we will have new therapies – perhaps the PCSK9 inhibitors – that further reduce risk. Before that, I would like to see the framework laid out for how you study an effective drug and how you come up with a rational strategy for allocating such a resource.
For more on the unintended effects of statins, read what study authors Shah Ebrahim and colleagues had to say in this BioMed Central guest blog.
Questions from Ursula D’Souza, Senior Editor for BMC Medicine.