The study, published in Heart, showed that 51% of patients prescribed statins did not achieve the 40% reduction in non-HDL cholesterol recommended by NICE and that these patients had a significantly greater risk of experiencing a cardiovascular event than those who did.
In a linked commentary, Dr Márcio Bittencourt from University Hospital Sao Paolo in Brazil, said the findings were 'clearly alarming'.
Using the UK Clinical Practice Research Datalink, researchers from the University of Nottingham identified 165,411 patients without cardiovascular disease who had been prescribed a statin between 1990 and 2016, and had at least one LDL cholesterol (LDL-C) measurement within 12 months before statin initiation and one measurement within 24 months after starting treatment.
The researchers defined the 51.2% of patients who did not achieve a 40% reduction in LDL-C as 'sub-optimal responders'. They found that the rate of cardiovascular events in this group was 22.6 per 1000 person-years compared with 19.7 per 1000 person-years in optimal responders, translating into a significant 22% adjusted increase in the risk of such events.
The study also found that every 1mmol/l reduction in LDL-C was associated with a 6% lower risk of stroke and mini stroke in the sub-optimal responders. However, achieving a 40% reduction in LDL-C was associated with a 13% lower risk of cardiovascular disease in general, which reinforced the benefits of the target, the researchers said.
Sub-optimal responders were more likely to be prescribed lower potency statins than those with an optimal response, the study also showed. For example, 29% of non-responders were taking low doses and 66% medium doses, compared with 18% taking low doses and 76% medium doses among responders.
The study did not take into account the effect of patient non-adherence and the authors acknowledge that this, combined with genetic factors, could explain the different results between the two groups.
However, they add that the 'findings nevertheless reflect real-world experience of treatment responses and outcomes for a large general population over time'.
Evidence from clinical trials suggests that responses to statins vary widely between patients and there are currently no guidelines for predictive screening before commencing treatment.
'Validated clinical decision tools which can predict cholesterol response to statins or to non-statin drugs, with interventions to help clinicians to tailor and optimise statin treatments for individual patients are needed,' the study authors concluded.
Dr Stephen Weng, assistant professor in integrated epidemiology and data science from the University of Nottingham's Division of Primary Care, who led the study with GP researchers, said: 'Our research has shown that in almost half of patients prescribed statins they are very effective and offer significant protection against cardiovascular disease.
'However, for the other half - whether it's due to your genetic make-up, having side effects, sticking to the treatment, or other medications – we don't see that intended benefit.
'We have to develop better ways to understand differences between patients and how we can tailor more effective treatment for those millions of patients who are simply blanket prescribed statins.'