(Even) more evidence for statins safety

At least once every week I find myself talking to a patient about their cholesterol levels, their risk of cardiovascular disease and whether or not they might need a statin. This isn’t surprising; we prescribe more people statins than any other medication, with around 9 million people receiving a regular prescription across England alone. Indeed, over time the number of people eligible for lipid-lowering treatment has increased with the latest NICE guidelines suggesting we ‘don’t rule out’ prescribing statins for some people with a QRISK score <10%.  

However, only 64% of people with a QRISK score ≥20% are prescribed lipid-lowering treatment.  Many patients are hesitant to take statins and hold concerns that they may cause significant side-effects. This partly reflects the long-term damage from previous scientific publications that have been picked up in the mainstream media and which misrepresent the harmful effects of statins. A quick online search finds news articles that highlight potential safety issues with statins, such as warning patients to ‘look out for droopy eyelids and double vision’ following an alert suggesting statin use could be linked with myasthenia gravis. Given these headlines, its no wonder people feel concerned about statin safety. The problem is that news stories tend to focus on potential side-effects, before a true link has been established and without balancing this against the benefits of statins. For example, one previous content analysis reported that two-thirds of right-leaning newspapers reported predominantly negative articles on statins. These stories often rely on observational data and may be subject to significant bias. Statin drug labels list a high number of possible side effects, often informed by these same post-marketing surveillance studies. Whilst this can help inform people of any potential issues with the drug, the long list can leave patients worrying. 

The results of a recent large Lancet meta-analysis that focused on adverse effects of statins are therefore of great interest. The study pooled individual patient level data from 124,000 participants across 19 randomised trials, each of at least 1000 participants, that had compared a statin to placebo. The included trials also had to be double blinded – neither the study team nor the patient knew if they were receiving a statin or placebo – which is important to avoid reporting bias, whereby people are on the lookout for known side-effects of a treatment. Focusing on these large, high-quality trials was intended to provide the most robust evidence possible. In contrast to observational studies, these randomised trials are also able to identify (or refute) causal links between statins and the outcomes of interest. 

The study team created a list of 66 potential undesirable effects of statins, based on the Summary of Product Characteristics of the five most widely used statins. The analysis found no link between statins and 62 of these 66 potential negative effects, including no link to sleep disturbance, memory loss, peripheral neuropathy, depression or sexual dysfunction. The four adverse effects that were associated with statin use were abnormal liver transaminases, other liver function abnormalities, oedema and urinary changes, such as proteinuria, albuminuria or microalbuminuria. The potential liver function changes are well recognised and the absolute risks small, in the order of around 1 in 100 patients, though with an increased risk at higher statin doses. The risk of oedema or changes in urinary composition were extremely rare and of uncertain clinical significance. It is important to note that there are additional established risks from statin use that were not re-evaluated in this study, including severe muscle damage, mild muscle symptoms and new onset diabetes. 

There are certain limitations with the data. Women were under-represented (28% of participants), mean age was 63 years and most participants were of white ethnicity, so we cannot be sure the results directly apply to wider patient groups. Median follow-up was 4.5 years so long-term adverse events might be under-estimated. 

However, overall this is an extremely robust and comprehensive review of statin safety and provides compelling evidence that the vast majority of potential adverse effects linked to statins are not in fact caused by the medication. The study team have put together a short video to share with the public to summarise the study findings. We can feel confident in reassuring patients about the overall safety profile of statins and the low risk of a limited number of adverse effects. Sadly, that might not be a very eye-catching newspaper headline….