A University of Nottingham study hit the headlines today after it suggested that statins – a drug that revolutionised the treatment of hypercholesterolaemia - are ineffective at lowering cholesterol to target levels in more than half of patients.

A wealth of evidence exists to support the safe and effective use of statins in patients with atherosclerotic cardiovascular disease but the study raised questions about the benefits of widespread use in individuals without cardiovascular disease.

A key detail in the results is that electronic health records cannot highlight all elements of real-life practice. Authors were quick to urge patients not to stop taking their medication and stated that genetic factors and patients not sticking to their medication may be an important explanation for this phenomenon.

Misconceptions about statins fuelled by false information?

The first statin to be approved for use was lovastatin in 1987 achieving peak annual sales of more than US $1 billion initially. The cholesterol-busting drugs now cost the NHS less than 10 pence per patient per day as generics became the drugs of choice.1

While the use of statins has increased substantially in the general population in recent years, appropriate uptake in high-risk groups remains suboptimal, with persistent disparities noted among women and racial/ethnic minorities.2

Recent research published in the Journal of the American Heart Association found that of those (26.5%) who were not currently taking statins, 59.2% reported that they had never been offered them and patients were more likely to report never being offered a statin if they were female (22% higher than others), black (48% higher than others).

Patients seen in cardiology practices were more likely to be offered a statin than those in primary care. It also found that many patients who could benefit from statins do not take them because of fear of side effects.2

The results prompted senior author of the study and assistant professor of Medicine at the Duke Clinical Research Institute, Ann Marie Navar, to state: "Although there are risks associated with statins, the public fear of side effects is out of proportion to the actual risks. Misconceptions about statins are everywhere and are fueled by false information on the internet. We need better tools to help combat this type of misinformation."

On such misconception or area of controversy is whether statin use is appropriate in patients aged over 75 years. The risk of heart attacks and strokes increases markedly with age, and yet statins are not utilised as widely in older people as they should be.  

A recent Lancet study found that statin therapy reduces major vascular events in people of all ages, including those over the age of 75. Since the risk of heart attack and stroke increases with age, the potential benefits are likely to be even greater for older people.3

A number of studies are now exploring whether statin treatment can prolong survival free of disability in a healthy elderly population.

Study results

The Notting University study, published in Heart, assessed the low-density lipoprotein cholesterol (LDL-C) response in patients after initiation of statins, and future risk of cardiovascular disease (CVD).4 It was a prospective cohort study of 165,411 primary care patients, from the UK Clinical Practice Research Datalink, who were free of cardiovascular disease before statin initiation, and had at least one pre-treatment LDL-C within 12 months before, and one post-treatment LDL-C within 24 months after, statin initiation.

According to the results, 84,609 (51.2%) patients had sub-optimal LDL-C response to initiated statin therapy within 24 months. During 1,077,299 person-years of follow-up (median follow-up 6.2 years), there were 22,798 CVD events (12,142 in sub-optimal responders and 10,656 in optimal responders). In sub-optimal responders, compared with optimal responders, the HR for incident CVD was 1.17 (95% CI 1.13 to 1.20) and 1.22 (95% CI 1.19 to 1.25) after adjusting for age and baseline untreated LDL-C. Considering competing risks resulted in lower but similar sub-HRs for both unadjusted (1.13, 95% CI 1.10 to 1.16) and adjusted (1.19, 95% CI 1.16 to 1.23) cumulative incidence function of CVD.

It concluded that optimal lowering of LDL-C is not achieved within 2 years in over half of patients in the general population initiated on statin therapy, and these patients will experience significantly increased risk of future CVD.

Yet it also revealed a significant therapeutic effect for the other 48.8% - statins in this group of patients were not only successful in lowering cholesterol by at least 4% but were more successful in preventing heart attack, stroke and narrowing of the arteries.

Prescribing practice

So what does this mean for prescribing practice going forward? Commentators have been quick to point out that there are complex reasons why patients chose not to take medication as prescribed and more research is needed to better understand why statins are not equally as effective in all patients.

NICE currently recommend daily use of atorvastatin 20mg in the primary care scenario when the estimated 10-year risk of cardiovascular disease, as assessed by QRISK2, is at least 10%.5 Guidelines from the American Heart Association/American College of Cardiology also recommend doctors use an atherosclerotic and cardiovascular disease risk calculator to give a detailed assessment of a person's 10-year risk for heart disease and to help create a personalised plan.6

In an accompanying editorial to the study,7 Dr Márcio Bittencourt and Fernando H Y Cesena from University Hospital and Hospital Israelita Albert Einstein, São Paulo, Brazil said that an important step after a guideline publication is the assessment of its uptake among health practitioners and patients in the real world, as well as of the impact of its adherence on clinical outcomes. 

They added: "Patients and society should be educated on the scientific evidence documenting the benefits of lipid-lowering therapy, and anti statin propaganda based on pseudoscience should be strongly disavowed and demystified by health authorities.”

RCGP chair Professor Helen Stokes-Lampard responded to the study by saying that GPs are highly-trained to prescribe and recommend drugs if they think they will genuinely help the individual patient, based on the specific circumstances affecting their health and their personal risk factors – and then after a frank conversation about the potential risks and benefits.

She added that mixed messaging around statins could be one of the reasons for non-compliance. "We would encourage anyone who is on regular medication to attend their scheduled medication reviews and to raise any queries or concerns they might have. But, given the widespread GP shortages and intense workload pressures that we currently have in general practice, it’s hard to know what more we can do to encourage greater compliance with medications that have been recommended in good faith."

 

Alison Bloomer is Managing Editor of GM Journal

 

  1. Hajar R. Statins: past and present. Heart Views 2011 12(3): 121–127
  2. https://jamanetwork.com/journals/jamacardiology/fullarticle/2583425
  3. Cholesterol Treatment Trialists' Collaboration. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. Lancet 2019; 393(10170): 407-415
  4. https://heart.bmj.com/content/early/2019/03/30/heartjnl-2018-314253
  5. NICE. https://www.nice.org.uk/guidance/ta94
  6. AHA. https://www.heart.org/-/media/files/health-topics/cholesterol/chlstrmngmntgd_181110.pdf
  7. https://heart.bmj.com/content/early/2019/03/30/heartjnl-2019-314723