UK’s NICE Recommends Lower-Risk Thresholds for Statin Therapy

(UPDATED) Statins may soon be more widely used in the United Kingdom following new recommendations from the National Institute of Health and Care Excellence (NICE).

The updated guidance, which is still in draft form, suggests that people with a 10-year risk of cardiovascular disease less than 10% might consider statin therapy if that’s their preference. Before physicians prescribe statins to these lower-risk people, there needs to be a discussion about the benefits of lifestyle changes and an attempt to modify all other cardiovascular risk factors, if possible.

Paul Chrisp, PhD, the director of the NICE Centre for Guidelines, said that for people with a 10-year QRISK3 score less than 10%, statins are an appropriate treatment to reduce that risk.

“We are not advocating that statins are used alone,” Chrisp stated in a press release. “The draft guideline continues to say that it is only if lifestyle changes on their own are not sufficient, and that other risk factors such as hypertension are also managed, that people who are still at risk can be offered the opportunity to use a statin, if they want to. They don’t have to, and their decision should be informed by an understanding of the risks and tailored to their values and priorities.”

Under the current NICE guidance, statins are only recommended for people with a 10% or greater 10-year risk of cardiovascular disease.

Darrel Francis, MD (Imperial College London, England), who wasn’t involved in drafting the new recommendations, is on board with the lower-risk threshold for therapy, noting there was no evidence to support the 10-year ASCVD risk threshold of 10% of greater. In fact, Francis had already begun prescribing statins in lower-risk patients in anticipation that the clinical guidelines would likely change.

“I think the guidelines have evolved in a nice way,” he told TCTMD. “I think it’s great that they’re opening up to more people.”

To add more years to someone’s life, said Francis, physicians need to start with LDL cholesterol-lowering when the person is young enough to accrue the benefits over time.

“The problem is that everyone who is young is low risk,” he said. “You could be a diabetic smoker, but if you’re young, you’re not going to have a heart attack in the next 10 years. It would seem like there’s no motivation to give them a statin, but it’s actually worthwhile because it’s stopping things that are going to give them problems in 20 or 30 years.”

NICE proposes physicians prescribe atorvastatin 20 mg for primary prevention if lifestyle changes are ineffective and the patient is amenable to treatment. They also recommend atorvastatin 20 mg in people 85 years and older but advise physicians to be aware of factors that might make treatment inappropriate, such as comorbidities, polypharmacy issues, general frailty, and life expectancy. Secondary-prevention guidance remains the same as the prior NICE recommendations.   

Starting Earlier Yields Greater Benefits

Kausik K. Ray, MBChB, MD (Imperial College London), president of European Atherosclerosis Society, said the NICE recommendations draw on the overwhelming evidence showing that statins, which are now cheaply available as generic medications, are safe and effective treatments for lowering the risk of atherosclerotic cardiovascular disease (ASCVD). Like Francis, Ray said targeting lower-risk patients will allow physicians to start primary prevention sooner.

It’s like jumping out of a building from the 50th floor but only starting to worry when you get to the 10th floor. Darrel Francis

“ASCVD results from lifelong accumulation of cholesterol in the vessel walls, and in this regard with a lifetime approach, earlier modest reductions maintained longer should afford greater benefits at the level of the population rather than treating more advanced disease, where multiple combinations of treatments will be needed to make up for lost years of cholesterol exposure,” he told TCTMD.

Based on data from the Cholesterol Treatment Trialists’ (CTT) Collaboration, lowering LDL-cholesterol levels by 1 mmol/L (38.7 mg/dL) lowers the risk of major vascular events by approximately 20%. However, Ray noted that among individuals with a 10-year risk of ASCVD of less than 10%, the relative reduction is approximately 33%.

“This means with less burden of atheroma, each 1-mmol/L lowering started early yields a greater return,” he said.

Ray added that current risk calculators are heavily weighted on age and using the 10-year risk threshold of 10% or greater inevitably leads to treating older people with more advanced ASCVD. “Lowering the threshold and having a discussion to explain risk and benefits means patients with low short-term but potentially high lifetime risk are likely to be offered medications to course correct and treat the underlying disease process earlier,” he said.

Under the current recommendations, many people are simply being treated too late, agreed Francis. He pointed out that regardless of risk factors, aging 10 years increases a person’s risk by approximately threefold while aging 20 years translates into a nine to 10 times higher risk of ASCVD.

“Why should we wait until people are nearly dead from coronary artery disease,” he asked. “You’re waiting until their coronary disease is so bad that it’s quite likely that in the next 10 years that they will have a heart attack or stroke. Then we say, ‘Ok, let’s start slowing it down now.’ It’s like jumping out of a building from the 50th floor but only starting to worry when you get to the 10th floor that this might not be a good idea.”

Colin Baigent, BMBCh (University of Oxford, England), the director of the Medical Research Council Population Health Research Unit that runs the CTT, said he welcomes the NICE update, noting that evidence from the randomized trials show statins are effective in people with a 10-year risk less than 10%.

He is also pleased the recommendations stress that muscle pain typically attributed to the medication is not caused by the drug at all. In 2022, Baigent and colleagues published data from an individual-level meta-analysis of nearly 125,000 people showing that statins were associated with a very small relative risk of muscle of pain and that this risk disappeared after 1 year of treatment. 

“Hopefully, this new guidance will result in many more currently healthy people choosing to take a statin long-term, since such a strategy has the potential to substantially reduce the risk of developing atherosclerotic disease later in life,” he told TCTMD via email. “In this way, we can ensure that the elderly of the future will have healthier hearts than their present-day equivalents.”

Some Concerns Raised

Martin Rutter, MD (University of Manchester, England), said the proposal from NICE does surprise him, particularly given the challenges currently facing the National Health Service (NHS). While there may be an economic analysis to support shifting treatment to lower-risk patients—economic considerations are part of NICE’s guideline-development process—Rutter has a number of concerns about the change.

For one, he is worried about the amount of work this will shift onto general practitioners, noting that it’s not as simple as writing a prescription. Risks and benefits have to be discussed, cardiovascular risk assessed, the impact of lifestyle intervention ascertained, and then long-term follow-up arranged.

“We’re just emerging from a pandemic,” he said. “It’s not been long since physicians are starting to get back to normal practice and routine. There’s a huge backlog of just managing disease in the community. My specialty is diabetes, for example, and we know there’s a lot of annual health checks that have been missed.”

Primary physicians’ time isn’t unlimited. Martin Rutter

Coupled with the need to catchup with the backlog, the number needed-to-treat to prevent ASCVD in this low-risk population is quite high. “Primary physicians’ time isn’t unlimited,” he said. “If they spend their time doing a particular activity, which is managing people at low risk for cardiovascular disease, something else is going to suffer. I don’t think that’s been considered in the guidelines.”

Additionally, the underuse of statins in people at higher ASCVD risk is well documented. For example, it’s been estimated that just 50% of people with a 10-year risk exceeding 20% are taking the LDL-lowering drugs. Focusing on higher-risk groups might be a more effective means to reduce the population burden of cardiovascular disease, said Rutter.

“My other concern is that this may exacerbate health inequalities,” he said. “I don’t want to label people the ‘worried well,’ but people who are more affluent, people who have health concerns, people who are better informed with better language skills are going to be the ones who engage with this sort of intervention.”

Increased Medicalization of Healthy People

To TCTMD, Rutter said he also worries about “overmedicalizing,” particularly very-low-risk individuals without any ASCVD risk factors, adding that there are people who will resist early treatment on this basis. Medical advice directed at lifestyle changes might be just as effective as starting them on atorvastatin, he said, adding that to his knowledge, there are no clinical trial data showing long-term statin benefits in very-low-risk populations (<5% 10-year risk for ASCVD).

“Cardiovascular disease is still a big issue, the leading cause of preventable death,” said Rutter. “In principle, I support the idea of doing what we can to prevent this disease, and the people who are going to be best served by this are higher-risk younger people who aren’t currently being identified through scoring methods, like QRISK. So, I don’t want to be completely negative about it. There is certainly some good here.”  

In one previous study, Francis found that a large number of people are willing to take a medication if it allowed them to live longer, but how much “disutility” they were willing to accept from having to take it varied. Some were only willing to take something if the increase in life span was very large. For that reason, Francis believes that starting statins should not be based on an arbitrary risk threshold. 

“We should be giving statins based on people’s willingness to take a preventative agent and let it be in their hands,” he said. “Let the people who want to take the extra protection take it—and I would take it—and those that don’t, don’t take it. It should have very little to do with their risk because the lifetime risk between a high-risk and low-risk person is very similar. The willingness to take a medication—the level of benefit in which you think it’s worthwhile—varies much, much more.”

Earlier modest reductions maintained longer should afford greater benefits at the level of the population rather than treating more-advanced disease. Kausik K. Ray

Francis acknowledged that lowering the threshold for treatment may end up medicalizing previous healthy people, but that is not a good enough reason not to offer them a statin. Instead, statin therapy should be viewed as a lifestyle choice, which would hopefully diminish some of the suspicions people might have around treatment. The stigma of medicalization could also be minimized if the administrative red tape were slashed. After a single consultation with a physician, patients should be able to get all their remaining refills without again speaking with a doctor; prescriptions could be sent automatically on a monthly basis.

Francis, who once proposed tongue-in-cheek that statins should be freely available at McDonald’s to offset the risk of junk food, said that changing lifestyle is a very difficult task for patients. While he stressed that they should try, there is a limit to how much physicians can wrangle with patients over diet and exercise.

“We don’t want them not coming to the doctor because they know we’re going to harass them about going out for a run,” he said. “We can say, ‘A run would be a good thing, but taking a statin is also a very good thing,’ and they can just get on with it.”

Francis said some regard statins as a “shortcut” to health, a puritanical criticism put forward by those who think people won’t eat healthy or exercise if prescribed a medication to lower cholesterol. He pointed out that there are other important paths to cardiovascular health—losing weight, improving blood glucose levels, and controlling blood pressure—that patients should pursue but that doesn’t mean statins don’t play a role.  

“Statins fix one part of the problem,” said Francis. “We shouldn’t make people suffer heart attacks for not being willing or able to lose weight.”