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Statins of small and uncertain benefit in primary prevention

Statins for primary prevention in people at low risk of CVD might be low-value care and waste of healthcare resources

Louise Prime

Thursday, 17 October 2019

Using statins for primary prevention, particularly in patients at low risk of cardiovascular disease (CVD) might be an example of low-value care and in some cases represent a waste of healthcare resources, researchers have argued in The BMJ today. They concluded in their analysis* that the prescription, use and reimbursement of statins in primary prevention warrants more careful consideration, incorporating patient preferences and number-needed-to-treat (NNT), because the benefits are small and uncertain and there are potential harms.

They pointed out that statins are now the most commonly used drug in the UK and one of the most commonly used medicines in the world. Although their use in people with established CVD “is generally uncontroversial”, their use for primary prevention remains debated – yet clinical guidelines in many countries have expanded eligibility criteria such that most people taking statins do so for primary prevention.

The authors’ own previous research examined the effects of changes to European guidelines on CVD prevention in a national cohort of older people in Ireland, and revealed that the proportion of over-50s who would have been eligible for statins increased from 8% based on the 1987 guidelines to 61% with the 2016 guidelines. The NNT to prevent one major cardiovascular event soared from 40 people at the lowest risk in the 1987 guidelines to 400 in the 2016 guidelines.

“Given the increased number of people taking statins and the dilution of benefit due to lower risk profiles of those being treated,” they said, “we need to assess and understand the evidence underlying these trends.” So, they undertook an overview of systematic reviews that examined the benefits of statins using only primary prevention data among 62-69 year olds taking them for 1-5 years.

They found that there were statistically significant reductions in all-cause mortality for people taking statins (relative risk, RR 0.91), vascular deaths (RR 0.85), major coronary events (RR 0.71) and major vascular events (RR 0.75). But, they argued, because an individual’s absolute risk reduction depends on factors such as age, sex, smoking status, cholesterol levels, and blood pressure, for clinical decision making it is more relevant to consider results stratified by baseline risk and sex. When considered in this way, statins did not have a statistically significant effect on most outcomes, “raising uncertainty about the benefits of statins for primary prevention in some subgroups of patients”. And, they said: “To further complicate matters, the systematic reviews report relative risk reductions… But the absolute risk reduction is more relevant to decision making for an individual patient.”

They contended that the trade-off between benefits and harms is especially relevant to people taking a statin for primary prevention, when the benefits vary considerably and for most might be “marginal at best” – although statins have clear benefits for high-risk groups, such as those with familial hypercholesterolaemia – because statin use can be associated with an increased risk of rare adverse effects including myopathy, rhabdomyolysis, diabetes, and haemorrhagic stroke, and the prevalence of milder non-specific side effects is still debated. They called for objective data on harms as well as benefits, without which doctors and patients cannot make fully informed decisions.

The researchers concluded: “Although statins are commonly prescribed, serious questions remain about their benefit and acceptability for primary prevention, particularly in patients at low risk of CVD. Statins, in this context, may be an example of low-value care (having little benefit and potential to cause harm) in these patients and, in some cases, represent a waste of healthcare resources…

“In the meantime, we argue that the prescription, use, and reimbursement of statins in primary prevention warrants more careful consideration, incorporating patient preferences and NNTs. More generally, the evidence on statin use for primary prevention suggests that the concepts of overuse and low-value care should become integral to policy making and resource allocation decisions.”

The Royal College of GPs said the research backs up its own concerns about changes to the risk threshold for statin prescription, and should be considered in future guideline updates. College chair Professor Helen Stokes-Lampard said: “The College has previously voiced concern around lowering the threshold for initiating statin therapy, which has significantly increased the number of patients eligible, due to the potential for overdiagnosis… As with all new research, it is important that the findings are considered as clinical guidelines are updated and developed, in the best interests of our patients.”

But she also stressed that statins are safe drugs and an effective preventative measure against CVD, when prescribed and used appropriately. She commented: “Like any medication, statins can have side effects, and some patients simply won’t want to take medication long term – but GPs are highly trained to prescribe and will only do so if they think it is in the best interests of the patient in front of them, and after a full and frank conversation about any associated risks and benefits. Patients certainly have the right to question whether statins are the best course of therapy for them – as they do with any prescribed medication – and as with any long-term medication, it’s important that regular reviews are undertaken to determine if they are proving beneficial for the patient, based on their current circumstances.”

*Byrne P, Cullinan J, Smith SM. Statins for primary prevention of cardiovascular disease. BMJ 2019; 367: l5674 doi: 10.1136/bmj.l5674

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